Chapter 1 Plant Systematics and Alkaloids

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PLANT SYSTEMATICS A N D ALKALOIDS DAVIDS. SEICILER The University of I ~ ~ i n o i s Urbana, Illinois

I. Introduction ........................................................ A. What Is Plant Systematics ? ....................................... B. Major Goals of Plant Systematics .................................. 11. Data to Be Utilized ................................................. A. Relationship of Chemical Data to Botanical Data .................... B. Rationale for Using Chemical D a t a . . ............................... C. Botanical and Chemical Literature ................................. D. Documentation of Plant Materials. . . . . . . . . . 111. Application of the Data to Biological Problems . A. Nature and Sources of Variation in Plants. .. B. Basic Pathways of Alkaloid Biosynthesis .... IV. Alkaloids in Lower Vascular Plants and Gymnos V. Alkaloids in the Angiosperms ......................................... A. Introduction ..................................................... B. The Magnoliopsida (Dicotyledonous Plants) .......................... ida (Monocotyledonous Plants) ...........................

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8 8 14 20 22 22 24 65 73

I. Introduction Many scientists, both chemical and biological, have sought to correlate chemical characters (i.e., the presence of certain types of compounds) with various botanical entities. I n the past, several factors have limited the success of such efforts, and it is only in recent years that such correlations have been applied to many plant groups. My purpose in this article is to review several of these earlier attempts as well as to examine current thinking in this area of endeavor. Several new ideas concerning the placement of selected plant groups within taxonomic systems will be discussed, and in addition, certain enigmatic problems that as yet cannot be clearly resolved will be posed as subjects for future investigation. As background t o these discussions, I will first describe the nature and goals of plant systematics t o provide the reader with the necessary perspective to understand the needs of that science.

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DAVID S. SEIOLER

A. WHATIs PLANT SYSTEMATICS ? Systematics is the scientific study of the kinds and diversity of organisms and of the relationships between them ( 1 ) .I n former times, much systematic work was based on the examination of preserved herbarium specimens in an effort to describe and classify various plant taxa (a term indicating taxonomic entities of unspecified rank). These studies frequently involved an examination of the form and structural features of relatively small numbers of specimens. Although this approach is still viable in many tropical areas of the world where rich and unstudied floras are in immediate danger of destruction or extreme modification (2, 3), it is largely being supplanted by examination of larger numbers of plants from living populations in temperate areas of the world, where the floras are better known. By means of this latter method, often called biosystematics, one attempts to study as much of the biology of the plant as possible and utilize these data to clarify the taxonomic and evolutionary relationships of the taxa involved ( 4 ) . The information derived from both approaches is normally utilized in two ways: to prepare floras of a particular region (often a state or large natural geographic region) or to account for all the species within a given group-for example, a genus or a family, regardless of where the plants grow ( 5 ) . Although each of the above aspects of systematics assists in identification and location of plant materials this information may also be invaluable to workers in many other fields such as chemistry, ecology, forestry, horticulture, floriculture, genetics, agronomy, zoology, entomology, or pharmacognosy, because of its predictive nature. Despite the introduction of many new approaches and technological advances, the basic systems of taxonomy that have been used for the last two centuries have not changed radically nor are they likely to undergo substantial modification. Movement of certain groups within the systems has occurred frequently. I n this chapter, the system proposed by Cronquist ( 6 )will be used as a basis for discussion, although frequent reference will be made to a number of other contemporary systems. Several of these systems (at the level of family and above) have recently been compared by Becker in Radford et al. ( 5 ) , and reference to that work will prove useful in understanding many taxonomic problems that will be discussed. B. MAJORGOALSOF PLANT SYSTEMATICS I n summary, the principal goals of plant systematics are to (a) provide a convenient method of identifying, naming, and describing

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plant taxa, (b) provide an inventory of plant taxa via local, regional, and continental floras, and (c) provide a classification scheme that attempts to express natural or phylogenetic relationships and t o provide an understanding of evolutionary processes and relationships ( 5 ) .In the subsequent parts of this chapter, I will present and discuss ways in which chemical data and in particular alkaloid chemical data can be utilized in meeting these goals. 11. Data to Be Utilized

A. RELATIONSHIP OF CHEMICAL DATATO BOTANICAL DATA As both morphological and chemical features are determined by genetics, the structure of a molecule must be as much a character as any other (7). Further, all the “characters” of a plant must be related and self-consistent. Thus, it is scarcely surprising that new cytological, numerical, and chemical data have provided valuable complementary information about the placement of groups within the taxonomic system rather than upsetting the results of extensive morphological investigations. How did these two types of characters arise and how do they differ Z I n the course of evolution the fate of any change in the genetic material of an organism will in large part depend on the function of the products produced. For example, changes in respiratory proteins, such as cytochromes, are unlikely t o survive, whereas changes in the enzymes that produce alkaloids or other secondary metabolic products are more likely to persist. The evolution of morphological and chemical features of an organism must be interrelated, but significantly, the forces of natural selection do not have the same effect on each type of genetic expression. These differences in selection are very important from a systematic standpoint because evolution of chemical constituents differs from morphological evolution, making the examination of both morphological and chemical characters an extremely valuable approach to the study of evolutionary problems (8).Because the structure of any compound is determined by a series of biosynthetic steps, each of which is under differing selective forces, not only may the structure of the compound itself be useful, but the biochemical pathway by which i t has arisen may be of systematic significance. B. RATIONALE FOR USING CHEMICALDATA The two major groups of compounds that have been applied to t,axonomic problems involve basically different approaches and appear

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DAVID S . SEIGLER

t o be useful in different manners. To date, these applications involve niacromolecules (in particular proteins) and micromolecules (mostly secondary metabolic compounds such as terpenes, flavonoids, alkaloids, cyanogenic and other glycosides, amino acids, and lipids of various types). When one utilizes macromolecules, he is examining the primary products of plant DNA and changes in amino acids within the protein reflect changes in the base sequence of the DNA. Initial studies of protein sequencing, especially those studies involving cytochrome C, indicate that this data provides valuable information about phylogeny and relationships a t the higher taxonomic categorical levels (families, orders, classes). Cytochrome c, which occurs in both animals and plants, has been sequenced in several species of animals (9). The fossil record for animals generally confirms information derived from these phylogenetic studies. The number of similarities in amino acids in particular positions in cytochrome c molecules from different animals makes it statistically improbable that they could have arisen from more than a single ancestral type with an ancestral cytochrorne c molecule. By tracing the differences in amino acid substitutions it is possible t o relate various groups of animals, as successive groups after a modification carry the changed cytochrome c molecule. I n plants, especially flowering plants, there is no extensive fossil record and much of the current knowledge of relationships and phylogeny in this group is based on extrapolation of studies of morphological data. To date, relatively few plant cytochromes have been studied, but in the few that have been investigated, it is apparent from the number of similarities of amino acid sequences that plant and animal G Y ~ O chromes are related. It is also evident that the sequences of amino acids in genera of the same family me more similar to each other than to those of other families and that families thought to be closely related by morphological evidence generally resemble each other more closely than less related families. The evolutionary history of plant groups, as well as of animals, appears t o be recorded in this and other proteins. Much recent work has established that micromolecular chemical data can also provide valuable insight into evolutionary processes ( 8 ) . Chemical studies of secondary products have proved useful in resolving many problems of specification and evolution but in contrast to protein sequencing data have generally been applied to the study of lower taxonomic categories, i.e., problems a t the species and genus level (10, 11). However, as will be pointed out, they may also be of value a t higher taxonomic levels. To understand how secondary compounds can be useful for the study

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of systematic problems, it is necessary to consider how and why they arose. Plants have a multitude of proteinaceous materials, many of which have enzymatic functions. In primitive organisms these compounds were and are largely active in synthesizing primary metabolic components of cells. As these organisms evolved, genetic material and its derived proteins were duplicated and increased both in amount and in redundancy. Mutations occurred that subsequently produced changes in the proteins and their products. The forces of natural selection operated on all such products (12), selecting them for value to and compatibility with parental organisms and the ecological systems in which they occur. Many of these compounds were of a less critical nature than primary metabolites and were less widely distributed. Complications are introduced because one does not observe the primary gene products, but rather pools of compounds they produce, the concentrations of which are partially functions of the relative amounts and activities of enzymes, the availability of certain precursors, and compartmentalization and translocation with the cell ( 4 ) . Subsequent mutations may affect steps in a biosynthetic sequence that we observe as an accumulation or disappearance of an altered product. These mutations usually involve the loss, gain, blockage, or alteration of the specificity of an enzyme system. Loss of synthetic ability is presumably more common than gain or alteration, since it merely implies destruction or blocking of a process instead of setting up a new one ( 7 ) . This is partially confirmed by the observation that in several groups of species from the related genera Parthenium, Hymenoxys, and Ambrosia of the Compositae, more highly evolved members have simplified patterns of secondary compounds (13).A one-gene loss may also block an entire pathway. The determination of homologous origin of similar compounds in different taxonomic groups is one of the fundamental problems inherent in the taxonomic application of secondary compounds. Two taxa may synthesize or pool the same products by different pathways; therefore, the mere presence of a compound is not necessarily an indication of relationship; i.e., similarities in the chemistry of plant taxa (or morphological features) may reflect an evolutionary or phyletic similarity but may also be the result of convergent evolutionary processes ( 4 ) . With a knowledge of biosynthetic pathways of secondary compounds in plants, it should be possible to determine a t what point in a sequence divergence has occurred and what subsequent changes have come to pass (7). In reality this is rarely realized because of several factors; several classes of compounds do not appear to have specific structural requirements, whereas in others less variation can be tolerated. For example, most phenolic substances could serve as antioxidants or many

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DAVID S. SEIGLER

lipid compounds for surface coatings as long as the necessary physical properties are met ; but attractants for specific pollinators or diterpenes with hormonal activities must be precisely synthesized (7). Many plant products arise by simple processes such as removal of activating groups (as phosphate or coenzyme A) or from oxidations, reductions, or methylations of easily modified groups (7). I n some cases the relative amounts of products produced may simply reflect the rates of two enzymes operating on a common precursor. Highly probable reactions, such as the introduction of an hydroxyl group ortho or para to an existing one in a phenol, occur frequently in nature. These types of changes are usually of only minor importance in considering the taxonomic significance of secondary compounds. Other reaction sequences are reversible or are controlled by feedback inhibition controls such that when a given compound disappears it disappears without a trace or causes accumulation of a compound far removed in the sequence. For example, polyketide chains, probably as coenzyme A esters, are rapidly reversible to their initial units unless some chemically irreversible stage is reached such as reduction or cyclization (7). In the fungus Penicillium islandicum which produces polyketide anthraquinones, mutation simply leads to the complete absence of these compounds. We have limited knowledge as to what pathways may be available in advanced plant groups as we can only see the products of those pathways that the plant utilizes a t a particular time. Several lines of work suggest that many plants are capable of carrying out complex reactions or reaction series but lack precursors or particular enzymes under normal situations. For example, when plants of Nicotiana are fed thebaine and certain other precursors of morphine they are able to perform several biosynthetic steps and produce morphine (14)which is not known to occur naturally in the genus. Interestingly, this conversion cannot be made by some species of Papaver, although other species of the genus contain thebaine and morphine. In assessing the importance of a particular change as an evolutionary step it is necessary to decide on the probability of its occurrence. As a general rule, the more difficult the reactions and the less available the building blocks or the more reaction steps required in a definite sequence to give rise to a compound, the rarer will be its convergent formation

(14). C . BOTANICAL AND CHEMICAL LITERATURE Many earlier publications were based on mass collections of materials, often gathered from large geographical areas and/or of uncertain origin.

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Frequently, only the major constituents-those that were poisonous, crystallized readily, or had other easily detectable properties-were examined. These facts must be considered by those who intend to apply the information to a taxonomic problem. Another difficulty in utilizing chemical data from the literature is a lack of reliability of certain structure determinations and in particular the identification of plant products by such physical properties as gas-liquid chromatography retention time, paper and thin-layer chromatography R, values, color reactions, and spot tests. Misidentification of compounds by wet chemical methods is not uncommon in the older literature before advanced spectral methods became available and must always be considered. One of the most serious problems in utilizing literature data is that almost no chemical reports are supported by adequately vouchered plant materials. Proper vouchering records would make it possible to examine the original materials and allow comparison with other collections in order to ascertain whether (a) the material was correctly identified and (b) certain phenomena, such as hybridization, introgression, or subspecific variations exist. It would also permit subsequent workers to determine the presence of fungi, lichens, algae, insects, etc., that may be involved in the production of certain secondary compounds. If a small portion of the actual materials utilized for the research is also preserved, it would permit later analysis for foreign contaminants. I n other cases, careful perusal of the botanical literature will reveal that taxonomists have placed taxa of various rank incorrectly. These incorrect placements may range from questionable or aberrant species in a genus to the realignment of entire orders of plants. Chemical data can assist in resolving problems of this type, but they sometimes provide enigmatic results until sufficient information is available to allow a reassignment of the taxa involved. One must look carefully and critically a t all reported data to be sure both chemical and botanical portions of the work have been done and interpreted correctly before applying the data to a problem under investigation.

D. DOCUMENTATION OF PLANT MATERIALS As mentioned in the preceding section, many early reports of alkaloids and other secondary compounds are suspect because accurate techniques required for assignment of complex structures were not available. Nonetheless, the major problem in using these data for systematic studies is not the reliability of the chemical data but the identity of the plant materials that were examined (15).

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DAVID S . SEIGLER

To document the materials used, the investigator should always have a competent person identify his plant materials and a portion should be dried or otherwise preserved as a voucher specimen so that further examination of the specimen is possible should it be desirable. The selected plant should be typical for the population and, when possible, should have mature reproductive organs. Full collection or acquisition data (data, location, collector, habitat, etc.) should be provided and the specimen deposited in a recognized herbarium. Taxonomists usually will be willing to assist with the necessary details of voucher specimen preparation. Most major universities have collections of dried plant specimens (a herbarium) that provide a wealth of data about the ranges, flowering t'imes, uses, soil preferences, and other information about particular species as well as preserving materials for future study or reinvestigation. I n publications describing chemical results, one should record the locations and dates of plant collections, the parts of the plants used in the study, the name of the herbarium where the voucher specimens are deposited, and the name of the taxonomist who identified the plants. With this information and with the possibility of comparing specimens collected a t other times with the original vouchers, later investigators can usually determine the relationship of the plants concerned to the original collection (15, 16). 111. Application of the Data to Biological Problems

A. NATUREAND SOURCES OF VARIATION IN PLANTS Until sensitive separation techniques (column, paper, thin-layer, and gas chromatography; countercurrent distribution; etc.) and sensitive methods of instrumental analysis (IR, NMR, UV, and mass spectrometry) became available, it was not feasible to undertake the analysis of secondary plant constituents from single plants of most species in naturally occurring populations. These new microtechniques permit the chemist or botanist to obtain chemical data from single plants rapidly, allowing the extension of the biosystematic approach to chemical as well as morphological characters. When phytochemical workers began to examine single plants, they were often frustrated by apparently uninterpretable variations of chemical constituents. Many of these investigators did not do adequate sampling, ignored the significance of these variations, and came to

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conclusions based on a meager amount of data in comparison to what was actually needed. Recent combined chemical and morphological investigations have used this information more fully and proved that, instead of being troublesome, the study of chemical and morphological variation actually provides a key to the solution of many problems of biological speciation, hybridization, and introgression.* Relationship between plant taxa is established by “ summarizing ” the similarities between groups of organisms and contrasting their differences. We consider two plants to be closely related if they have many common characters and only distantly so (or at higher categorical levels) if the differences outweigh the similarities. In contrast to this, the name of the game in evolution is change and the ability to maintain variability. Few natural populations are without measurable variation; that is, plants from interbreeding groups that share a gene pool have phenotypic and genotypic differences that can be seen even by inexperienced observers. How do these variations arise and how are they maintained ! Each individual plant must possess the ability to respond to its environment, but this variation must remain within the limits set by the genetic makeup of the taxon (12, 1‘7). Thus, phenotypic expression is determined by both genotypic composition and reaction to a specific environment. Some characters are little changed by environment--e.g., leaf arrangement or floral structure-and these have been considered “good characters” or to be “genetically fixed.” Other characters are known to vary radically and are said to be “phenotypically plastic.” Examples of characters of this type are leaf shape, stem height, and time of flowering. The effects of environment are superimposed on and may obscure genotypic variability; further, it is the phenotype produced by both that is is exposed to the pressures of natural selection. Davis and Heywood ( 1 7 ) have listed a number of important physical factors in determining the appearance of a plant in nature. Among these are light, seasonal variation, elevational differences, terrestrial versus epiphytic state, photoperiodism, temperature, temperature periodic effects, water (heterophylly), wind, soil (e.g., halophytes), and biotic factors such as fungal and bacterial infection, ant habitation, galls, grazing and browsing, fire, and trampling. The population is considered by many to be the basic evolutionary * Introgression is the process by which the genes of one taxon are mixed with the

genes of another by hybridization of the two taxa followed by backcrossing of the hybrid plants with either of the two parents. Even when hybrids are not significant in relative numbers, they can allow gene flow and mixing, producing increased variability of the two parental types.

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unit and when we discuss speciation and concomitant chemical change it is necessary to understand something of the nature of variation both within and among populations of a given taxon or group of taxa. Populational variations are a function of the variation of individual plants and of the common gene pool that they possess. Morphological and chemical features enable us to recognize the population, but they do not define it. It must also be remembered that the population is a dynamic entity. It changes in numbers of plants and, even in some perennials, in the particular individuals present in a given year. A population may occupy a much larger geographical area in some years than others. It may separate into two or several new populations under some conditions that may be maintained or later merge with the parental population. Taxonomic descriptions are sometimes based on a single plant specimen, which may not reflect the nature of the species or its populations. Several factors are important in determining genetic variation. Mutations usually produce a one-gene change, but these changes may have profound effects. Such changes as zygomorphic corollas t o actinomorphic corollas in Antirrhinum, the gamosepalous to polysepalous condition in Silene, spurred t o nonspurred flowers in Aquilegia, and annual to biennial condition in Atropa are all known to be controlled by one gene ( 1 7 ) . Most mutations affect several characteristics of the phenotype. Thus, a species may differ from another in several characters but still may be separated by only a one gene difference. Characters that have no selective advantage in themselves can become established through the secondary effects of genes that have been selected as valuable to the organisms for completely different reasons ( 1 7 ) .Certain genetic variants coexist in temporary or permanent equilibrium within a single population in a single spatial region in a phenomenon known as polymorphism ( 1 7 ) . Recombination of genetic variability in populations is largely determined by the breeding system. Cross-fertilized populations contain a large store of variability hidden in the form of recessive genes in the heterozygous condition. This variability serves as insurance in the presence of a constantly changing environment. I n sexual populations breeding tends to take place principally between neighboring individuals. I n summary, the three factors that largely control variation in populations are (a) external environmental modification, (b) mutation, and (c) genetic recombination ( 1 7 ) . Populations rarely stay the same over a period of time but are affected by the process of natural selection in a stabilizing, disruptive, or directional manner. Populations separated by geographical, ecological, or reproductive barriers will tend to differ-

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entiate into a series of populations that may have gradually accrued differences (clinal variation) or stepwise variations associated with ecological differences (ecotypic variation) (17). If the differences between populations increases sufficiently, and especially if reproductive barriers arise, these differentiating populations may be recognized as species. Stebbins ( 1 2 ) considers four major factors in speciation: (a) mutation, (b) genetic recombination, (c) natural selection, and (d) isolation. I n small, often peripheral populations, chance may play a greater role in speciation because the probability of loss of a particular character is greater; recessive genes are more likely to appear and become homozygous, and the genetic nature of the population may be determined by the “founders” or “survivors” of a period of catastrophic selection. These phenomena explain many of the variational patterns observed in the distribution and occurrence of secondary plant compounds, especially at the lower taxonomic ranks, and although they have mostly been examined by means of morphological characters, much evidence suggests that evolution and speciation may be studied or measured by chemical characters as well. I n the preceding discussion, variation of morphological characters has been considered. There is no reason t o think that variation in chemical characters has not occurred and is not maintained in a similar manner. I n contrast to morphological features, however, the specific structures and steps of biosynthetic pathways are easier to quantify and generally simpler in terms of genetic control (at least in principle). Secondary compounds are affected by environmental as well as genetic factors (18, 19). In a study of alkaloids of the genus Baptisia (Leguminosae), Cranmer studied the variation of lupine alkaloids during the development of individual plants in different populations of Baptisia leucophaea Nutt. ( 2 0 ) . Individual plants in each population exhibited considerable quantitative variation, while plants from different populations were similar at similar stages of development. However, there was striking variation in the specific alkaloids produced, the relative amounts of each, and in the total quantity of alkaloids present a t any given time in development. Nowacki encountered similar variation in lupine alkaloids in the genus Lupinus ( 2 1 ) . A number of workers have examined the genetics of alkaloid production by the study of hybrid plants (14, 21-25). These results indicate that the genetic mechanisms that control alkaloid synthesis are complex and that hybridization and introgression can produce significant variations in the alkaloid content of plants within a population. Many past workers have been unaware of natural hybridization and, because these plants are occasionally indistinguishable from the parental species,

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have not been able t o interpret the alkaloid patterns observed (14, 15). Hybridization and introgression in the genus Baptisia has been extensively studied by workers a t the University of Texas. Several populations that contained all possible hybrid combinations, plants derived from back-crossing these plants with the parental plants, and the parental plants were examined. The status of these plants was established by independent methods; subsequently the alkaloid chemistry was examined. The data indicated that the hybrid plants not only failed to exhibit the alkaloid chemistry of the parent species either singly or combined, but also showed some striking quantitative variation among individual hybrid plants. Mabry concludes that this variation is extremely useful and represents one of the best available techniques for detecting and documenting natural hybridization and introgression (26). Extensive variation can occur in the different parts of an individual plant ( 2 7 ) . Changes associated with the reproductive parts of a plant are often striking; these organs also exhibit the greatest amount of morphological change during a plant’s growth and development. Cranmer and co-workers (20, 28) observed that in Baptisia species alkaloids often showed greater variation between organs of plants from a single species than between the same organs for different species. The total yield of alkaloids from different organs was also shown t o vary significantly. The most thoroughly investigated plants in this regard are medicinally important ones such as Papaver somniferum L. and solanaceous plants of the genera Nicotiana, Atropa, Hyoscyamus, and Datum (27). At the present time our lack of knowledge of the specific enzymology of the synthesis of secondary metabolites prevents direct comparison of many of the pathways involved in various taxa. Examination and comparisons must frequently be restricted t o those systems ascertained t o be related by other reasoning, such as a knowledge of the structures of other compounds derived from and part of the biosynthetic pathways in the same and related species of plants. Secondary compounds have classically been viewed as waste or excretion products ( l a ) ,but a body of information is accumulating that suggests that many have important coevolutionary defensive and attractive roles (29-31) as well as primary metabolic importance (32-34). The forces of natural selection seldom operate on a single organism but on a total biological system. This is undoubtedly one reason convergence in the evolution of both morphological and chemical characters is observed. It is well known, for example, that certain habitats are occupied by

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plants that possess similar morphological features (12, 27, 35-38). It has not been definitely established, but it appears that various chemical components of plants can be seiected to produce convergence of chemical types. One example that confirms this possibility is that Ammodendron conollyi Bge., a legume native to Central Asia, contains the alkaloids ammodendrine (1)and sparteine (2), and another plant from

COCH, 1

that area, Anabasis aphylla L., a member of the Chenopodiaceae, contains similar alkaloids such as lupinine (3),aphyllin (a), and anabasin ( 5 ) .I n the legume, cadaverine (and hence lysine) serves as a precursor

0 3

4

5

for both types, whereas in Anabasis, the quinolizidine alkaloids are formed as in legumes but anabasine is derived from nicotinic acid as in Nicotiana. Thus, what might appear to be a close similarity is in reality an analogous route to the same compounds ( 1 4 ) . I n another example, three species of the genus Hymenoxys (Compositae), H . scuposa (DC.) K. F. Parker, H . acaulis (Pursh) K. F. Parker, and H . ivesianu (Greene) K. F. Parker, contain more than thirty flavonoids. The patterns of distribution of these compounds are correlated more strongly with population positions along an east-west gradient extending from Arizona to Texas than with the diagnostic morphological features of the species. The biochemical parallelism observed for populations of different species in the same region suggests the action of common selective forces (39). It has been observed that small, isolated island populations of mainland taxa usually have fewer and simpler compounds than their mainland ancestors. This may be because of lowered selection by predation or because island habitats have different environmental requirements (35).

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B. BASICPATHWAYS OF ALKALOID BIOSYNTHESIS In the preceding section we have surveyed some of the ways in which variation originates and is maintained in plants. A knowledge of these variations is extremely important in systematic studies a t the lower taxonomic levels (genus-species), but when one wishes to establish relationships a t higher ranks, e.g., at the family, order, and subclass level, it is necessary to survey as many taxa and individuals as possible to reduce the effects of these variations. That is, we need to know what morphological features are produced and what biosynthetic pathways exist in a particular group of taxa to compare them. This is made more difficult by our imperfect knowledge of biosynthetic pathways, but, by careful observation of their products, we can establish certain relationships. I n this chapter we will mostly consider the application of alkaloids to systematic problems. Other secondary compound data can prove equally usable and should also be considered in a complete study of the relationship of systematics and secondary compounds. I have necessarily addressed those problems for which alkaloid data appear to be most helpful or promising and have not pursued certain relationships that may be more clearly established by other chemical and morphological data. I n this section I will survey some of the fundamental and widespread pathways of alkaloid biosynthesis. Studies of many of these compounds have proven useful a t lower taxonomic ranks but, due to the widespread appearance and presumably simple biosynthetic origin, are not as valuable for delineating the higher categorical levels, although in a few cases compounds that appear to be very simple are observed to have limited distributions. The simplest alkaloids are several amines derived from common amino acids such as phenylalanine, tyrosine, histidine, tryptophan, lysine, ornithine, and anthranilic acid. Alkaloids containing simple aromatic moieties and some of their simply derived relations have been reviewed (40-46). These simple amines arise by decarboxylation of the corresponding amino acids, often with subsequent methylation, hydroxylation, and addition of other groups. They are widely distributed, and their presence is usually not of taxonomic significance at the higher taxonomic ranks. These compounds are important because they are frequently beginning points for the synthesis of more complex alkaloids. Phenylalanine gives rise to phenylethylamine (6) and the corresponding methylated compound (7),while tyrosine produces the corresponding compounds tyramine (8) and N-methyltyrosine (9). I n the Gramineae tyramine is converted to hordenine (lo),which is widespread

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6

8

in 1 is family ,ut not restricted to it. Tyrosine is also converteL to two other important intermediate compounds, dihydroxyphenylalanine (DOPA) (11) and its cyclic derivative, cycloDOPA (12). These compounds are especially common as intermediates in the synthesis of alkaloids of the benzylisoquinoline and betalaine types as well as alkaloids widely distributed in the Cactaceae (47, 48) (see Section V, B). I n the Rutaceae many of these simple aromatic compounds are converted to the corresponding amides, such as fagaramide (13) from

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Fagara xanthoxyloides Lam. Although most gymnosperms do not contain distinctive alkaloids (with the notable exception of the Taxaceae and Cephalotaxaceae), the genus Ephedra (Ephedraceae), a group only distantly related to more common gymnosperms, contains methylated phenylethylamines such as 1-ephedrine (14) and d-pseudoephedrine (15), which are also characteristic of this group of plants but not restricted to it (49-52). CH3

I

HCNHCH,

I

8 HCOH

14

CH3

I

HC-NHCH,

I

0

HO-C-H

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DAVID S. SEIGLER

The simple aliphatic compounds putrescine and cadaverine, derived from ornithine and lysine, respectively, are intermediates in the synthesis of many major groups of alkaloids and presumably occur in many plant groups but are seldom isolated and studied. Ornithine (or its successor N-methylputresine) gives rise to N-methylpyrrolidine via the reactions below (53). CHa-NH,

CHaNHCH3

CHa

CHa

CHa

+ CHS

I

I I

CHNH,

I

COaH

I

I I CHNH, I

-con

CHaNHCH3

I

CHa

I

CH,

I

__f

CH,-NH,

COaH

CHaNHCH3

A similar reaction series can produce the corresponding piperidine homolog from lysine. These compounds are easily alkylated by a number of compounds, for example, p-ketobutyric acid, to produce simple alkaloids such as hygrine (16) of the pyrrolidine type (43-55). I n a similar manner attack on an N-methylpiperidium cation yields

16

N-methylisopelletierine, an intermediate in the formation of characteristic alkaloids in the Punicaceae, Lythraceae, and Lycopodiaceae. Simple pyrrolidine and piperidine alkaloids are widespread among higher plants. Both groups may serve as substrates for additional alkylation reactions either internally to yield alkaloids such as tropine (17) and pseudopelletierine (18) or intermolecularly to yield more complex alkaloids. Pyrrolidine alkaloids are widespread, no doubt a reflection of the relatively small number of biosynthetic steps and chemical probability of their synthesis, but they are characteristically proliferated in a few families, such as the Solanaceae and Erythroxy-

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laceae and less commonly in others such as the Euphorbiaceae and Convolvulaceae and doubtfully in the Dioscoreaceae (49-52, 56, 57). Alkaloids of the piperidine type are more widely distributed. Many simply derived ones are found in the Crassulaceae, Punicaceae, and the Leguminosae, but they are also found in the Pinaceae, Euphorbiaceae, Chenopodiaceae, Equisetaceae, Piperaceae, Caricaceae, and Palmae.

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Alkylation by phenylpyruvic acid may occur to produce other alkaloids characteristic of the Crassulaceae, such as sedamine (19) (53) and lobeline (20), found in the genus Lobelia of the Campanulaceae. Nicotinic acid may also alkylate the pyrrolidinium cation to produce compounds such as nicotine (21), one of the most widely distributed of all alkaloids (43, 50, 58). Many related compounds are found in the Solanaceae, especially in the genus Nicotiana. Anabasine (5) arises in Nicotiana by alkylation of the lysine-derived piperidinium cation. Coniine (22), the principal alkaloid of Conium (Umbelliferae), closely

20

0

22

18

DAVID S . SEIGLER

resembles intermediates in the synthesis of the isopelletierine alkaloids but has been demonstrated to be derived via a polyketide pathway (53, 59) from acetate precursors. This is a clear example of convergence in the types of compounds produced and it demonstrates why a knowledge of biosynthetic pathways is valuable in studies of phylogeny. Coniine has been reported from several other families (50).It would be especially interesting to determine the path of synthesis in each of these. Simple derivatives of tryptophan are also widely distributed in nature. Some, such as serotonin (23) and bufotenine (24), involve subsequent oxygenation. N,N-Dimethyltryptamine (25) and psilocybin (26) are widely known for their hallucinogenic properties. These compounds are more restricted in distribution than 23 and 24; 25 is 7H3

24

23

0-

I

HO-P=O

25

26

found in several families (50-52), but 26 appears t o be limited to fungi. Tryptamine and its derivatives serve as intermediates for many groups of alkaloids and by inference must occur in numerous plant taxa. Another group derived from tryptamine is the /?-carboline alkaloids,

--Q-,2&

Q - + . L O Z H ' N

N

H

H

OTJ /N

CH30 \

H

H 27

1.

19

PLANT SYSTEMATICS

which occur in many plant families such as the Passifloraceae, Symplocaceae, Zygophyllaceae, Eleagnaceae, Malphigiaceae, Euphorbiaceae, and Loganiaceae. Many families which contain alkaloids of the /3-carboline type are otherwise devoid of alkaloids. Histamine (28) is widespread in higher plants, but only a few alkaloids derived from the parent amino acid histidine, such as pilocarpine (29)) are known otherwise. Alkaloids of this type are mostly restricted to the Rutaceae (Casimiroa and Pilocarpus) and certain groups of fungi.

28

29

Dimerization of intermediate compounds from ornithine and subsequent cyclization can lead to the basic skeleton of the pyrrolizidine alkaloids (53). Further elaboration of basic pyrrolizidine structures Ornithine + putrescino

HCO'

involves the type of oxidative process noted previously in relation to the biosynthesis of pyrrolidine and piperidine alkaloids. Pyrrolizidine alkaloids are usually esterified with mono or dibasic acids, many of which are unique to this series, e.g., heliosupine (30) and senecionine (31)(49-52, 60-64). Alkaloids of this type are found in several families CH3 H

H3C'foH HO--CCHOH--CHB

I c=o I

30

31

20

DAVID S. SEIGLER

b u t are characteristic of the Boraginaceae (several genera), the Compositae (tribe Senecioneae), and the Leguminosae (Crotalaria)(49-52, 60-64). Similar reactions with cadaverine, derived from lysine, produce lupin alkaloids such as lupinine (3). I n this instance the corresponding aldehyde may condense with another molecule of piperidine t o yield more complex compounds such as lamprobine (32),sparteine (Z), and matrine (33).Alkaloids of this type are best known from certain genera of the Leguminosae (28, 49-52, 65).

32

33

I n this section several fundamental pathways of alkaloids biosynthesis have been examined. We will make frequent reference t o these in the subsequent examination of a number of specific taxonomic problems because all have been observed to occur in many higher taxonomic groups.

IV. Alkaloids in Lower Vascular Plants and Gymnosperms Alkaloids are rarely found in lower plant groups. Algae, bryophytes, and ferns seldom contain compounds of this type. Among the lower vascular plants there are two notable exceptions; one is the genus Lycopodium, which contains complex alkaloids such as lycopodine (34) derived from lysine by means of precursors similar to those involved in the formation of pelletierine alkaloids in the Punicaceae (49-52, 66-69). The other exception is the genus Equisetum, which contains several alkaloids, such as palustrine (35). Nicotine (21) is also reported from Equisetum species. Although alkaloids are relatively uncommon among gymnosperms, simple compounds such as pinidine (36) are found in the Pinaceae and closely related families. The biosynthesis of compounds of this type has been previously outlined (Section 111, B). The Taxaceae (Taxales) (70) and Cephalotaxaceae (Cephalotaxales) (72, 72, 72a) contain alkaloids such as taxine (37),which is possibly

1.

PLANT SYSTEMATICS

21

34

of diterpine origin, and deoxyharringtonine (38),which are restricted to their respective families (and orders). The homoerythrina alkaloids of the Cephalotaxaceae are otherwise known only from the families Aquifoliaceae and Liliaceae (73, 7 4 ) . Both groups of alkaloids have antitumor activity and are extremely toxic.

nu

0

6H

1

31

OCH,

R = CH

CH-CHa-CH2C(OH)4H2COpMe

I co;

3 - ~

CH3 38

The presence of complex alkaloids in the Taxaceae and Cephalotaxaceae supports the separation of these orders from other gymnosperms. This separation has been suggested by several workers on both paleobotanical and morphological grounds (75-77). Although the fungi represent a distinct evolutionary line and are

22

DAVID S . SEIGLER

probably as distant from plants as they are from animals in evolutionary terms ( I ) , they do possess several interesting types of alkaloids. Many ofthese compounds, such as psilocybin (26), which is found mostly in the genera Psilocybe and Stropharia, are derived from simple amines which are also widespread in higher plants. Muscarine (40) is a hallucinogenic choline analog found in the fly mushroom, Amanita muscaria. Others, such as gliotoxin (39) from Trichoderma viride, are more

CH,OH 39

40

complex in structure. Many nitrogen-containing compounds from Fungi imperfecti, especially the genera Penicillium, Streptomyces, and Aspergillus have pronounced antibiotic activity; these have been reviewed elsewhere (49, 50, 78-80). Indole alkaloids of the ergot type are found in Claviceps and also in t'he angiospermous plant family Convolvulaceae (Section V, B).

V. Alkaloids in the Angiosperms A. INTRODUCTION Among the Angiosperms (flowering plants), Cronquist recognizes six subclasses of dicotyledonous and four subclasses of monocotyledonous plants ( 6 ) .Alkaloids are scarcely known from some of these, whereas in others they are common. Among the subclasses of Magnoliopsida (dicots)the Hamamelidae and Dilleniidae have few alkaloids-primarily simple bases and 8-carboline types that occur in many plant groups. Benzylisoquinoline alkaloids are characteristic of many orders of the subclasses Magnoliidae, although some tryptophan-derived bases are found in a small number of families which do not contain alkaloids of the benzylisoquinoline type. Diterpene alkaloids are found in several genera of the Ranunculaceae. The Caryophyllidae contain alkaloids derived from tyrosine and the corresponding dihydroxyphenylalanine (DOPA). Both simple types

1. PLANT SYSTEMATICS

23

and betalain pigments occur and their presence is characteristic of many families of the order. The situation is more complex in the subclass Rosidae, where families of some orders synthesize alkaloids and others do not. Those that produce significant numbers and types of alkaloids are the Rosales (Leguminosae and Crassulaceae), Myrtales (Lythraceae, Punicaceae), Proteales (Eleagnaceae), Cornales (Garryaceae, Alangiaceae), Euphorbiales (Buxaceae, Euphorbiaceae, Daphniphyllaceae, and Pandaceae), Celastrales (Celastraceae), Rhamnales (Rhamnaceae), Sapindales (Rutacae and Peganum of the Zygophyllaceae), Linales (Erythroxylaceae), and Umbellales (Conium of the Umbelliferae). There is little unity among the types of alkaloids produced by this group of plants. The extremely large and diverse family Leguminosae produces many types of alkaloids, among them are pyrrolizidine (Crotalaria), physostigmine (Physostigma), quinolizidine (several genera), Erythrina types (Erythrina),and Ormosia types (Ormosia). The Lythraceae produce an interesting type of quinolizidine alkaloids not known from other plants; the Punicaceae produce alkaloids similar to the better known tropane types; and the Garryaceae produce diterpene alkaloids, otherwise found principally in the Ranunculaceae. The Buxaceae contain alkaloids derived from triterpene skeletons. Euphorbiaceae is an extremely diverse family in terms of alkaloid types; in this regard, it is only rivalled by the Leguminosae and Rutaceae. Benzylisoquinoline, indole( ?), emetine( ? ), securinine, nicotine, polypeptide, Alchornea alkaloids, tropane, p-carboline, and simple bases are all known to occur within the family. The Daphniphyllaceae contain diterpene alkaloids of a unique type only known from this small family. The Pandaceae, Rhamnaceae, and Celastraceae contain alkaloids with attached polypeptide units. In the subclass Asteridae, many orders produce alkaloids. Among these are the Gentianales, Polemoniales (Solanaceae and Convolvulaceae), Lamiales (Boraginaceae), Campanulales (Campanulaceae), Rubiales (Rubiaceae), and Asterales (Compositae). The Gentianales and Rubiales are noted for prolific production of indole alkaloids and less for others of the tylophorine, monoterpene, and quinine type. The Solanaceae are known for the production of steroidal, tropane, and nicotine types, whereas a related family, the Convolvulaceae, produces both tropane and ergot alkaloids. The Boraginaceae and the tribe Senecioneae of the Compositae and Crotalaria, a genus of legumes, produce highly toxic alkaloids of the pyrrolizidine type. The genus Lobelia of the Campanulaceae synthesizes alkaloids of an unusual type restricted to that genus.

24

DAVID S. SEIGLER

B. THE MAGNOLIOPSIDA (DICOTYLEDONOUS PLANTS) 1. Introduction

The presence and phylogenetic significance of more advanced alkaloid groups in the various subclasses and orders of dicotyledonous plants (Magnoliopsida, sensu Cronquist) will now be examined. As the simple alkaloids previously discussed (Section 111, B) are of lesser significance from a systematic view, their presence will only be mentioned when appropriate, and numerous records of these compounds, which may be useful a t the lower categorical levels, will be omitted. The Caryophyllidae are probably the most primitive group and will be examined first, followed by the Magnoliidae and Rutaceae. The Hamamelidae, which do not contain alkaloids of complex structure, are omitted, as are all families of the Rosidae except for the few that contain alkaloids, i.e., the Leguminosae, Euphorbiaceae, Daphniphyllaceae, and Erythroxylaceae. Following this, a number of alkaloid types based on terpenoid structures will be examined. Most of these occur in families of the Asteridae, the most advanced subclass according to Cronquist, although some orders, such as the Cornales (sensu Cronquist), and a number of families of the Rosales possess the same iridoid compounds and certain of their alkaloidal derivatives. Members of the Nympheaceae (Magnoliidae, Sensu Cronquist) have sesquiterpene type alkaloids. The Garryaceae (Cornales, subclass Rosidae) and the genera Delphinum and Aconitum (Ranunculales, subclass Magnoliidae) as well as a few other isolated groups contain alkaloids based on a diterpene structure. The Apocynaceae (Holarrhena), the Buxaceae (Euphorbiales, subclass Rosidae), the Solanaceae, and many Liliaceous plants (of the Liliopsida) contain alkaloids based on steroidal and triterpenoid structures. Alkaloids based on tryptophan and monoterpene-iridoid structures and their distribution mostly in the families Apocynaceae, Loganiaceae, and Rubiaceae (all subclass Asteridae) will be reviewed. The relationship of alkaloid chemistry and systematics in several families of the Asteridae is then examined, e.g., the Solanaceae and the Convolvulaceae. The distribution of ergot alkaloids in the latter family and the fungal genus Claviceps is discussed. 2. The Caryophyllidae

The subclass Caryophyllidae is recognized by Cronquist as having

4 orders, 14 families, and about 11,000 species. Of these orders, the

Polygonales, Plumbaginales, and Batales are largely without alkaloids

1.

25

PLANT SYSTEMATICS

although harman, tetrahydroharman, and harmanine have been reported from a species of Calligonum of the Polygonaceae (50). I n contrast, alkaloids are widespread in most families of the Caryophyllales. They have been reported from the Aizoaceae (2500 species), Amaranthaceae (900 species), Basellaceae (20 species), Cactaceae (2000 species), Chenopodiaceae (1500 species), Didieraceae ( 9 species), Nyctaginaceae (300 species), Phytolaccaceae (150 species), and Portulaceae (500 species), but not from Caryophyllaceae (2000 species) and Molluginaceae (100 species). Because of the considerable controversy concerning the relationship of chemistry to the classification of this order, it has been studied more extensively than many others. Saponins are widely distributed through the order. They have been reported from the Aizoaceae, Molluginaceae, Amaranthaceae, Basellaceae, Cactaceae, Caryophyllaceae, Nyctaginaceae, and Phytolaccaceae. Many of these are based on triterpene aglycone skeletons (78, 81). Some species of the Chenopodiaceae contain a number of simple alkaloids derived from phenylalanine, tyrosine, tryptophane, ornithine, and lysine. Alkaloids derived from tyrosine are of particular interest because they are related to both benzylisoquinoline alkaloid precursors and precursors of the betalain pigments which are widespread in the order (37, 4 4 , 5 8 ) .Salsolin (41) is an example of an alkaloid of this type. Several relatively simple piperidine derivatives are found, as well as the '

41

alkaloid anabasine (5), which in this instance is structurally but not biosyntheticalIy related to nicotine. Lupinine (3) and other quinolizidine alkaloids are found in Anabasis aphylla. Alkaloids with structures similar to those derived from tyrosine above are widely distributed in Caetaceae (43, 49-52, 78, 81). One of these, mescaline (42), is widely known for its hallucinogenic properties. Others such as anhalidine (43) and anhalonidine (44) show similarity to

OCH, 42

OH 43

44

26

DAVID S. SEIGLER

certain precursors of benzylisoquinolinealkaloids. Other, more complex, alkaloids involving mevalonate units such as lophocerine (45) and dimerization of simple alkaloid units occur.

45

The genus Mesembryanthemum and related genera of the Aizoaceae contain alkaloids such as mesembrine (46), which are also derived from tyrosine (82).

46

CH,

The most widespread alkaloids of the order, however, are betalain pigments derived from L-DOPA (83).These red or yellow compounds have ultraviolet absorptions in the same ranges as anthocyanins and probably serve much the same function in plants of the Caryophyllales. The occurrence of the two classes of compounds is mutually exclusive; no known plant in a betalain-containing family has ever been shown to contain anthocyanins and vice versa (26, 83-87). The families Caryophyllaceae and Molluginaceae contain anthocyanins, a fact that has been used to suggest that they should be segregated into a closelyrelated but distinct order (87). The red-violet pigment of beets is betanin (47) whereas the related yellow pigment from the cactus

HO

/

47

$

C0.H

48

27

1. PLANT SYSTEMATICS

SCHEME 1

Opuntia ficus-indica Mill. is indicaxanthin (48). The first of these compounds arises via Scheme 1. Once formed, betanin may be converted t o other compounds via routes similar to those shown in Scheme 2. Based on both chemical and morphological evidence, Mabry considers that the " Centrospermae families " (the Caryophyllales without the Caryophyllaceae and Molluginaceae) were derived from a common ancestral line from some precursor of the angiosperms and that this major

48

SCHEME 2

28

DAVID S. SEIOLER

evolutionary line gives rise to two lines, one anthocyanin containing, the other betalain containing (87').The early evolutionary divergence of the Caryophyllales and Polygonales from other angiospermous lines is supported by protein sequencing data of Boulter (88).The similarity of cytochrome c amino acid sequences suggests that the Polygonaceae (Polygonales) and the Caryophyllales are more closely related to each other than either is to other plants that have been sequenced. The postulated early origin of the Centrospermae is also in accord with studies based on both morphological and chemical features by other workers (78, 89-92) but does not agree with the origin of this group as postulated by Cronquist ( 6 ) ,who suggests that it is derived from the Magnoliidae. Both this data and benzylisoquinoline alkaloid data suggest that the Magnoliidae are not ancestral to the other subclasses of Angiosperms, with the exception of the Rutaceae and a few other families. 3. The Magnoliidae

The subclass Magnoliidae as defined by Cronquist consists of 6 orders, 36 families, and more than 11,000 species, and in his view, they are

the most primitive of the angiosperms (flowering plants), evolutionarily speaking. The Aristolochiales and Papaverales have not been included with the other four orders by many workers [see Becker's comparison of taxonomic systems in Radford et al. ( 5 ) , p. 6171 but were included by both Takhtajan (69) and Cronquist ( 6 ) principally on the basis of morphological characters. Before discussing the alkaloids and systematics of this large group, it will be helpful to consider major morphological features that separate the orders of the subclass as well as their major chemical constituents. The Magnoliales are all woody plants that possess specialized cells that contain essential oils. These oils are primarily of terpenoid and phenylpropanoid origin. The nature of numerous chemical constituents of the Magnoliales as well as other orders of the Magnoliidae have been reviewed (78, 81). Several families have scarcely been examined, and

LslERiDAE ROSlDLE

CARlOPHlLLlDlE

YAGNOLl IDLE

FIG.

1 . Subclasses of Magnoliopsida according to Cronquist (6).

1.

PLANT SYSTEMATICS

29

little can be said of the value of chemical characters for establishing their taxonomic position. Among these are the Amborellaceae (1 species), Austrobaileyaceae (2 species), Canellaceae ( 16-20 species), Degneriaceae ( 1 species), Schisandraceae (47 species), Trimeniaceae (7-1 5 species), and Winteraceae (95-120 species). When one compares the numbers of species in the remaining families, it is evident that a t least several species of the larger families have been examinedAnnonaceae (2100 species), Calycanthaceae ( 9 species), Eupomatiaceae (2 species), Hernandiaceae (50-65 species), Himantandraceae (2-3 species), Illiciaceae (42 species), Lauraceae (2000-2500 species), Magnoliaceae (215-230 species), and Monimiaceae (450 species). Members of the orders Piperales and Aristolochiales also have specialized oil cells, but in contrast to the Magnoliales are mostly herbaceous plants. The families of the small order Piperales, the Saururaceae (5-7 species), Piperaceae (1490-3000 species) (Cronquist accepts about 1500), and the Chloranthaceae (65-70 species) are generally low in alkaloid content but rich in compounds derived from phenylalanine or tyrosine metabolism via cinnamic acid and its relatives. The Aristolochiales, which consist of one family, the Aristolocbiaceae (600 species), are rich in compounds derived from the metabolism of cinnamic acid, p-coumaric acid, and their relatives but also contain many alkaloids. The Nympheales are aquatic plants that do not possess the oil glands typical of the three previously described orders. Some workers have considered the Nelumbonaceae to be sufficiently distinct so as to comprise a separate order, usually called the Nelumbonales ( 6 ) . Cronquist separates the Nelumbonaceae ( 2 species) from the Nympheaceae (65-93 species) (but retains both in his order Nympheales), largely on a basis of morphological characters, and the chemistry of these two groups has not been investigated with the exception of their alkaloids. The Ceratophyllaceae (4-1 0 species) has been little studied chemically. The Ranunculales also lack ethereal oil glands and most species of the order belong to three large families-the Ranunculaceae, Berberidaceae, and Menispermaceae. I n morphological features they are generally more advanced than the Magnoliales and are probably derived from them ( 6 ) . Chemical constituents from the three large families Ranunculaceae (800-2000 species), Berberidaceae (600-650 species), and Menispermaceae (350-425 species) have been studied extensively, but the remaining families of the order have been little examined. These are the

30

DAVID 5. SEIGLER

Circaeasteraceae ( 1 species), Lardizabalaceae (30-35 species), Coriariaceae (10-1 5 species), Corynocarpaceae (4 species), and Sabiaceae (90-1 60 species). The Papaverales consist of two families, the Papaveraceae and the Fumariaceae, which are advanced in many respects within the Magnoliidae. Cronquist considered the two families to be parallel groups that show different individual specializations a t least partly because of the absence of the latex system, which is well developed in the former family but missing in the later. These two medium-sized families have about 600 species ( 6 ) . Plants in these families excel in their ability to synthesize alkaloids of various types, but other constituents of the two families have not been examined to any great extent. Despite the widespread occurrence of compounds derived from phenylpropanoid metabolism and the almost ubiquitous presence of sizable quantities of terpenes within plants of the subclass, the presence of alkaloids derived from tyrosine and phenylalanine, namely those of the benzylisoquinoline type, more clearly defines the subclass. The general pathways leading to these benzylisoquinoline alkaloids have been reviewed (53, 93-98). This system arises from tyrosine (or phenylalanine?) in plants of the Magnoliidae by condensation of 3,4dihydroxyphenylethylamine and 3,4-dihydroxyphenylpyruvicacid and a subsequent Mannich condensation to yield norlaudanosoline (49) as the primary condensation product. This compound is subsequently methylated and desaturated to produce papaverine (50) in the opium poppy, Papaver somniferum (53, 93, 94). Methylation appears to occur after formation of the tetrahydrobenzylisoquinoline system but before dehydrogenation to papaverine. Norlaudanosine occurs with papaverine and also serves as an efficient precursor for its formation (53). Simple benzylisoquinoline alkaloids are known to occur in the Annonaceae, Hernandiaceae, Lauraceae, Magnoliaceae, Menispermaceae, Monimiaceae, Papaveraceae, Euphorbiaceae, Rhamnaceae, and Rutaceae (49-52). d-Reticuline (51), which is known to serve as an HO

HO HO

HO

CH30 49

CH30 60

51

31

1. PLANT SYSTEMATICS

intermediate in the biosynthesis of several more highly modified series of compounds is widely distributed and is known to occur in the Anonaceae, Hernandiaceae, Lauraceae, Monimiaceae, and Papaveraceae as well as the non-Magnoliidean family Rhamnaceae (49-52). Aporphine alkaloids [e.g., glaucine (53)and bulbocapnine (54)] have essentially the same distribution as simple benzylisoquinoline types (49-52) and arise by ortho-para coupling of compounds such as laudanosoline (52) (53, 94, 99-101) or where ortho-para coupling is not possible via the intermediacy of proaporphine compounds such as orientalinone (55) in the biosynthesis of isothebaine (56) in Papaver orientale L. (53,93,102).Aporphine alkaloids are known to occur in the CH,O

CH,O

CH3

CH,O

HO OCH, 53

OH 51

54

cH30w HO

56

32

DAVID S. SEIGLER

Berberidaceae, Ranunculaceae, Fumariaceae, Aristolochiaceae, Magnoliaceae, Lauraceae, Hernandiaceae, Monimiaceae, Menispermaceae, Nelumbonaceae, Papaveraceae, Symplocaceae, Euphorbiaceae, Rutaceae, and the Rhamnaceae. Morphine alkaloids, such as morphine (57), also arise by ortho-para coupling of compounds such as 1-reticuline (58) in the family Papaveraeeae (53,93,94,103-108).Certain intermediates in this pathway occur in other families, for example, salutaridine (59) in Croton salutaris Casar of the Euphorbiaceae.

OH 58

57

I n Cryptocarya bowiei (Hook.) Druce, an Australian member of the family Lauraceae, benzylisoquinoline precursors yield compounds with closure to the isoquinoline nitrogen such as cryptaustoline (60) (53,109). In the family Papaveraceae, various species of the genera Argemone and Eschscholtzia synthesize alkaloids from benzylisoquinoline pre-

HO

60

0 59

33

1. PLANT SYSTEMATICS

cursors with another type of closure. Representatives of these are Z-eschscholtzine (61) and Z-munitagine (62) (53, 93, 94, 96, 110). I n the closely related Fumariaceae, closure occurs to include an oxygen atom ring of cularine (63) (48, 93, 94, 103).

?H

62

61

,

OCH, 63

The genus Cocculus of the Menispermaceae synthesizes alkaloids of the Erythrina type. Alkaloids of this type are known t o arise in the genus Erythrina (Leguminosae) by complex rearrangements of benzylisoquinoline alkaloids such as N-norprotosinomenine (53, 93, 94, 111115). The N-methyl carbon atom of several benzylisoquinoline alkaloids is known to participate in formation of a " berberine bridge " in compounds such as berberine (64)(116,117).Although protoberberine alkaloids are known to occur in several families (Anonaceae, Ranunculaceae?, Aristolochiaceae, Magnoliaceae, and Menispermaceae), they are characteristic of the genus Berberis (Berberidaceae) and of the genera Corydalis and Dicentra of the Fumariaceae (49-52). Stylopine (65)in the

34

DAVID S. SEIGLER

65

66

latter two genera is converted to protopine (66)(118).The benzophenanthridine skeleton encountered in a number of alkaloids of the Papaveraceae is also derived from benzylisoquinoline precursors (48, 93, 94). Chelidonine (67)is an example of this type of alkaloid. Phthalideisoquinoline alkaloids, e.g., narcotine (68), are also found in the Papaveraceae and Fumariaceae with occasional occurrences in the Berberidaceae and Ranunculaceae (49, 53, 93, 94, 119). Coupling of benzylisoquinoline units occurs in an intermolecular as well as in an intramolecular fashion (53,93,94,120,121).The individual components are usually linked by one or two diphenyl ether bridges.


/

o

67

’

OCH,

0

OCH,

68

The distribution of compounds of this type is essentially the same as for the simple benzylisoquinoline units and aporphine alkaloids; they are found in the Menispermaceae, Lauraceae, Magnoliaceae, Monimiaceae, Hernandiaceae, Nelumbonaceae, Aristolochiaceae, and Ranunculaceae, with a questionable record from the Buxaceae (49-52). Aristolochic acid (69) occurs in the Aristolochiaceae and is often accompanied by aporphine alkaloids. Feeding studies have demonstrated that this naturally occurring nitro compound is probably derived from orientalinol (70) (94). Further, noradrenaline is incorporated into aristolochic acid with good incorporation rates, suggesting that 4-hydroxynorlaudanosoline is a precursor and that the 4-hydroxyl group is required for oxidation of the heterocyclic ring.

1. PLANT SYSTEMATICS

70

35

69

Many botanists agree that the orders of the Magnoliidae according to Cronquist are related and derived from common ancestors. This conclusion is largely based on morphological evidence, and chemical evidence i s considered supplemental, although in the subclass only the order Piperales and the order Nympheales (if one removes the Nelumbonaceae) lack either the simple benzylisoquinoline alkaloids or their more highly evolved derivatives. The Piperales are closely linked to other orders by the presence of many phenylpropanoid and terpenoid compounds as well as morphological features. The Nelumbonaceae are linked by the presence of benzylisoquinoline alkaloids to other orders of the subclass, but the other families of this order, especially the Nympheaceae, do not possess compounds of this type but rather alkaloids with a sesquiterpene skeleton. Because of the presence of ellagic acid and the absence of benzylisoquinoline alkaloids, Bate-Smith believes that the family Nymphaeaceae is completely out of place in this subclass (122),a view shared by some other workers (89-91). Pathways leading to benzylisoquinoline alkaloids are found in many (but not all) families of the remaining orders. Within these orders the presence of these types of alkaloids is observed because the plants that contain them descended from common ancestors and not because the pathways have evolved numerous times. The families Magnoliaceae, Annonaceae, Eupomatiaceae, Monimiaceae, Lauraceae, and Hernandiaceae of the Magnoliales contain benzylisoquinoline alkaloids. The families Himantandraceae, Myristicaceae, and Calycanthaceae contain alkaloids of other types, 71,26, and 72, respectively, and do not contain benzylisoquinoline alkaloids. At least one species of the Winteraceae contains alkaloids of an undetertermined type (123),whereas species of the Degeneraceae, Austrobaileyaceae, and Trimeniaceae have been tested and found not to contain alkaloids (78, 1234. The Lactoridaceae, Canellaceae, Illiciaceae, Schisandraceae, Amborrelaceae, and Gomortegaceae have apparently not been tested. The families Ranunculaceae, Berberidaceae, and

36

DAVID S. SEIQLER

Menispermaceae contain benzylisoquinoline alkaloids, while members of the Lardizabalaceae (123u, 123b), Corynocarpaceae (123a), and the Coriariaceae (123~-123c)have been tested and found not to contain alkaloids. The Sabiaceae and Circaeasteraceae have apparently not been tested. The families Aristolochiaceae (Aristolochiales)and the Papaveraceae and Fumariaceae (Papaverales) all contain benzylisoquinoline alkaloids as previously mentioned.

8"

HC


72

Other lines of reasoning demand that certain families with other types of alkaloids [the Myristicaceae, Calycanthaceae (124), and Himantandraceae] must be accorded a place in the Magnoliales, but if so, what is their status! Have they lost the ability to synthesize benzylisoquinoline alkaloids and taken on the ability to synthesize others ? Or are they derived from non-benzylisoquinoline alkaloid synthesizing ancestors ? Similar questions may be asked about those families with no alkaloids, i.e., the Degeneriaceae and Trimeniaceae of the Magnoliales; the Lardizabalaceae, Coriariaceae, and Corynocarpaceae of the Ranunculales; the entire order Piperales; and the Nympheales exclu Nelumbonaceae. The complexity of structures derived from simple benzylisoquinoline skeleta is generally in accord with the origin of the orders as proposed by Cronquist. The simpler types of alkaloids are found in families of the Magnoliales and more highly derived compounds are found in the Aristolochiales on one hand and in families of the Ranunculales and Papaverales on the other (125). Certain genera and species within each of the above groups lack alkaloids. These should probably be interpreted as cases where mutations or metabolic changes have produced blocks to particular lines of biosynthesis. It is also possible that, for some unknown reason, other biosynthetic lines have been favored and the machinery needed to make

1.

37

PLANT SYSTEMATICS

benzylisoquinoline alkaloids sits unused. Examples of this are the genus Aniba of the Lauraceae, which appears to utilize the precursors that most Lauraceous plants convert into alkaloids to make compounds such as 6-styryl-2-pyrones, cinnamides, and neolignans; many species of the Piperaceae; certain species of Asarum of the Aristolochiaceae; and Podophyllum of the Berberidaceae (125). The distribution and taxonomic significance of benzylisoquinoline alkaloids within several families of the subclass have been reviewed. The distribution of alkaloids in the Lauraceae has been studied by Gottlieb (126). The family was subdivided into two subfamilies by Kostermans (127).I n the subfamily Lauroideae, the tribe Perseae seems capable of synthesizing only the most primitive types-those with the benzyltetrahydroisoquinoline skeleton. I n contrast, the tribe Cryptocaryeae can make numerous alkaloids, e.g., aporphines, 1-( w aminoethyl)phenanthrenes, benzylisoquinolines, bibenzpyrrocolin, and pavine types, as well as pleurospermine (73) and compounds similar to tylophorine (74). The other two tribes, the Cinnamomeae and Litseae, are in an intermediate position. The other subfamily, the Cossythoideae,

OCH, OCH,

73

74

consisting mainly of vines, is clearly different as it contains oxyaporphines and a morphine type alkaloid. The chemistry and distributions of phenylpropanoid derivatives, which seem to supplant the alkaloids in certain taxa, is discussed in detail in that work (125, 126). The treatment of Kostermans is largely upheld by data of alkaloid, phenylpropanoid, terpene, flavonoid, and other chemical origin. The distribution and systematic significance of alkaloids in the Menispermaceae has been recently reviewed (128).The alkaloids of this family are closely related to those of the Berberidaceae, Papaveraceae, Annonaceae, Rutaceae, and Ranunculaceae both in the type and range of alkaloids in agreement with Cronquist’s placement of this family. The family contains several unique types, such as the hasubanan skeleton (75) (which have the opposite configuration to that found in morphine

38

DAVID S. SEIGLER

types) and others of the Erythrina type such as dihydroerysodine (76) that are otherwise known only from the Leguminosae. I n contrast to the findings of Gottlieb in the Lauraceae, there is not such clear-cut correlation between the occurrence of specific alkaloid types and the subfamilies of the Menispermaceae [as proposed by Engler (129)],although the hasubanan, morphine, Erythrina, and novel bases are only found in tribes of the subfamily Menispermeae.

/ \

CH30

-

CH3

0

CH30 75

‘OH

76

There has been considerable debate in the past about the placement of the Papaverales in this subclass. This argument has largely been resolved by means of morphological characters, although the chemistry of this order closely resembles that of the Magnoliidae and especially the Ranunculales from which Cronquist supposes them to be derived (5-7). These alkaloids range from simple bases to some of the most complex structures derived from the benzylisoquinoline skeleton. Some of these (e.g., the protopines) are found in both the Papaveraceae and Fumariaceae, whereas other types are found only in the Fumariaceae (e.g., cularine, ochotensine, and sendaverine alkaloids) or only in the Papaveraceae (e.g., the papaverrubrin, pavine, isopavine, and benzophenanthridine types). Cronquist does not feel that the Papaveraceae and Fumariaceae are clearly distinct on purely morphological grounds, but the differences in chemistry strongly suggest that they are distinct a t the familial level (66, 81). Probably no other genus has been examined for the presence of alkaloids as extensively as Pupawer (Papaveraceae) (110); comprehensive reviews (108, 130, 131) have surveyed the results of alkaloid determinations in many species. Morphologically distinct seetions of the genus also have distinct alkaloid chemistry (110). In another genus, Argemone, subgeneric groupings are less distinct and chemistry does not clearly resolve them (110).This evidence does suggest that Argemone is derived from ancestors that had pavine-type alkaloids. The variation of alkaloids at the specific and subspecific or infra-

1. PLANT SYSTEMATICS

39

specific levels in plants of this group has been reviewed extensively because of their medicinal importance (14, 37, 78, 81, 107, 110). The effects of many environmental and genetic factors surveyed in Section I11 are reviewed by TBt6nyi (110).Within individual species quantities of alkaloids may be modified drastically by environmental factors but normally not the types produced. Many of these variations must be accounted for if one wishes to utilize alkaloid chemical data to study problems a t the specific or subspecific levels in the Papaveraceae. 4. The Rutaceae

The Rutaceae is one of the more interesting and complex families with regard t o alkaloid chemistry as well as the formation of flavonoids; mono-, sesqui-, and triterpenes; furocoumarins; and other secondary compounds (78, 81). The family contains alkaloids based on several major biosynthetic pathways, such as benzylisoquinoline (tyrosine), quinoline (132), furoquinoline (133),quinazoline (134), acridine (135) (anthranilic acid), imidazole (histidine),indoloquinazoline (tryptophan), and both simple aliphatic and aromatic amines (53, 93, 136-138). Quinoline and furoquinoline alkaloids are especially widespread within the family, being found in four of the five subfamilies from which alkaloids have been reported (136).Neither the furoquinoline, acridine, or indoloquinazoline alkaloids, which are derivatives of anthranilic acid, have been reported from sources other than this family (78, 81). Most reports of quinoline alkaloids are also from the Rutaceae. Benzylisoquinoline alkaloids occur widely in the Magnoliidae (Section V, B) and also in the Rhamnaceae, Euphorbiaceae, and Celastraceae. Engler (129) divided the Rutaceae into seven subfamilies-the Rutoidae, Dictyolomatoideae, Spathelioideae, Toddalioideae, Aurantioideae, Flindersioideae, and Rhabdodendroidae. Willis (139) felt that the groups that make up the Rutaceae differ to the extent that some could be regarded as independent families. Airy-Shaw (140)and Prance (141) recognized the Rhabdodendroideae as a close relative of the Phytolaccaceae; little, if any, chemical work has been done on this group. The Flindersioideae and Spathelioideae have been elevated to familial level and the former taxon placed in a position intermediate between the Rutaceae and the Zygophyllaceae (142), but recent evidence (137, 143, l 4 4 ) , largely based on alkaloid structures, suggests that both the Flindersioideae and the Spathelioideae should be maintained in the Rutaceae. Moore in Hegnauer (145) contended that the Rutoideae is a highly complex subfamily phylogenetically and that the present classification of the Rutaceae is one which runs directly C<

40

q

DAVID 5. SEIOLER

0

CH3

OCH,

CH,O

*J

OCH,

\

Acronycine (an acridine alkaloid)

Skimmianine (a furoquinoline alkaloid)

Qyq6

Or$

Casimiroine (a quinoline alkaloid) CH,O

OCH,

N

Arborine (a quinazoline alkaloid)

/

/

\

OCH3

Hortiacine (an indoloquinazoline alkaloid)

5-Methoxyoanthin-6-one (a canthinone alkaloid)

f Pilocarpine (an imidazole alkaloid)

across the lines of specialization in floral anatomy." Waterman, in agreement with Moore's work, states that Engler's classification of both major subfamilies Rutoideae and Toddalioideae is untenable and proposes a new scheme of classification (137). Support for the view that the Rutaceae is a distinct and homogeneous group is provided by its essential oils and coumarins. Essential oils and coumarins are found in a t least four subfamilies. This view is also

1. PLANT SYSTEMATICS

41

confirmed by alkaloid chemical data: (a) furoquinoline alkaloids are essentially ubiquitous in the family and acridones are also widespread; (b) magnoflorine (77) and berberine (a), two of the most common alkaloids in the Ranunculales and the Magnoliales, occur in species of Rutaceae along with the chelerythrine (78), which is characteristic of the Papaveraceae. CH,O HO

OCH,

CH,O 77

78

O Y O C H , OCH, 79

80

Alkaloids of the benzylisoquinoline type are mostly found in the genera Zanthoxylum (including Fagara), Phellodendron, and Toddalia. These three genera, which Engler placed in the Rutoideae-Zanthoxyleae, Toddalioideae-Phellodendrinae,and Toddalioideae-Toddaliinae,respectively, are closely related with an apparent phylogenetic link between Toddalia and Zanthoxylum (137). I n the Boronieae (Rutoideae), only furoquinolines are produced, whereas in the Diosmeae (Rutoideae) none are found. I n the Ruteae (Rutoideae)no less than five types of alkaloids are common to the three major genera. Alkaloids of the 1-benzyltetrahydroisoquinolinetype are assumed to be primitive in the Rutaceae and thus the genera producing them are the most primitive extant genera of the family (78,89-91).As anthranilate-derived alkaloids are found in the same genera, it appears that the evolutionary trend was for direct replacement of one type with another (137). The genera of the Rutaceae that do not have l-benzyltetrahydroisoquinoline alkaloids, e.g., the Diosmeae, Boronieae (Rutoideae), and Aurantioideae, must be relatively advanced.

42

DAVID S . SEIQLER

The Rutaceae have been regarded by many as being especially close to the Zygophyllaceae, Cneoraceae, Meliaceae, Burseraceae, and Simaroubaceae ( l 4 5 ) ,and Cronquist considers the family to be a member of the order Sapindales, subclass Rosiidae ( 6 ) .No other families in this order contain significant quantities of alkaloids, essential oils, or coumarins, with the exception of the genus Peganum (Zygophyllaceae), which contains alkaloids of the harmine and quinazoline types, although these are not directly analogous to the alkaloids of the Rutaceae (78), Picrasma ailanthoides Planch (Simaroubaceae) which has been reported to contain 4,5-dimethoxycanthin-6-one(79), and Ailanthus giraldii Dode (Simaroubaceae) (3-dimethylallyl-2-quinolone)(80).The Rutaceae are chemically linked to the Meliaceae and the Simaroubaceae by a number of triterpenes and their derivatives. These compounds are derived from tirucallol(81) (or euphol, which has the opposite configuration a t C-20) and have highly oxidized skeletons that often render their recognition as triterpenes difficult (78, 94, 146).

81

The Burseraceae is known t o contain many essential oils rich in mono- and sesquiterpenes as well as triterpenes but does not contain the modified structures found in the preceding three families (78, 86). The Cneoraceae has not been studied chemically to any degree. The fact that the related families Simaroubaceae, Cneoraceae, and Meliaceae lack alkaloids suggests that they are relatively advanced with respect to the Rutaceae (137). This is partially confirmed by studies of the triterpenes of these families. Thus far, we have addressed ourselves to systematics within the family and to a discussion of what the close relations of the Rutaceae might be. Next we will examine several possibilities for the origin of the family. If our assumption that benzylisoquinoline alkaloids are primitive within the family is true, then we would anticipate (a) that the family is derived from ancestors that possessed benzylisoquinoline alkaloids, (b) that the pathways for these compounds evolved in some proto-Rutaceous species that were ancestral to other members of the group, or (c) that they evolved from ancestral species -that

1. PLANT SYSTEMATICS

43

possessed the necessary pathways to synthesize alkaloids but failed to express them and later in ancestral Rutaceous stock they became turned on once more. As previously mentioned, Cronquist (6)and other phylogenists (6, 69, 142, 147) generally place the family in the Sapindales or in similar groupings, such as the Rutales (sensu Taktajan). Few of the plants of these orders possess alkaloids of the appropriate type, nor do most members of the Rosales, hypothetical ancestors of the order. At this point we must either accept possibilities (b) or (c) above, or look for other possible ancestors. Several other workers (78, 89-91, 145) have postulated that the origins of the Rutaceae lie in the Magnoliidae, near the Ranunculales or Papaverales (145). While this appears unlikely to many it should be noted that this decision has been reached by several investigators (88, 148) on strictly morphological grounds. 5. The Leguminosae

The family Leguminosae, as defined by Cronquist, is a member of the Rosidae and one of the largest plant families with about 13,000 species. Takhtajan, Stebbins, and Hutchinson considered the group to be sufficiently distinct to comprise a separate order (12,69,142).The three subfamilies that make up the family, the Mimosoideae, Caesalpinoideae, and Lotoidae, have all been elevated to familial ranks by various authors. Most investigators have seen a fairly close relationship between the Leguminosae and Rosaceae. The family has many interesting secondary plant compounds, but none that characterize the family as a whole nor any that establish a close relationship to the Rosaceae. The alkaloids of this large plant family have recently been reviewed by Mears and Mabry (15). These compounds are widespread throughout the former but are largely missing from the latter family. Simple amines derived from phenyalanine, tyrosine, and tryptophan are widespread throughout the Leguminosae but are most commonly found in the subfamily Mimosoideae. Derivatives of the preceding amino acids occur in the genus Acacia and are also found as oxygenated and methylated derivatives, e.g., candicine (82), phenylethylamine, tyramine, and tryptamine in the genera Desmodium and Lespedeza. Physostigmine (83), a representative of an unusual type of alkaloid with great pharmacognostic value, is isolated from Physostigma venenosum Baifour, the Calabar Bean (15, 149, 150). Quinolizidine alkaloids are widespread in certain tribes of the subfamily Lotoideae, among which are the Genistae, Podalyrieae, and

44

DAVID S. SEIGLER 0

OH 8%

83

Sophorae. Although some of these alkaloids, such as lamprobine (32) and retamine (84), are restricted in distribution, the compounds lupinine (3), cytisine (85), and sparteine (2) are widespread in these tribes (15, 28). Cranmer and co-workers (20, 28) have presented arguments that the presence of lupine alkaloids in the Lotoideae suggests they originated from a common ancestral stock that contained a gene

85

84

pool for synthesizing these compounds. More complex derivatives of simple quinolizidine alkaloids have limited distributions in related genera. Matrine (33) and sophoramine (86)are only found in the genus Sophora and a few related genera. Related alkaloids, e.g., ormosamine

86

(87), are found in the genera Ormosia and Piptanthus. Although these genera have been placed in the tribes Sophoreae and Podalyrieae, respectively, the presence of complex pentacylic alkaloids suggests some relations (15). Pyrrolizidine alkaloids have a similar mode of origin to quinolizidine types, and it is not surprising that the genus Crotalaria (tribe Crotalinae), which is related to the quinolizidine-containing genera, synthesizes

1.

PLANT SYSTEMATICS

45

a7

these alkaloids. The Boraginaceae and the tribe Senecioneae of the Compositae also contain pyrrolizidine alkaloids. The biogenesis of Erythrina alkaloids has been reviewed (111-115). These alkaloids are derived from benzylisoquinoline alkaloids by complex rearrangements (53, 93, 94) and are known only to occur in the genus Erythrina and in certain genera of the Menispermaceae. The presence of sphaerocarpine (88) in Ammodendron has led Mears and Mabry (15)to suggest that this genus should be relocated with the

CH,O " O

W

N

q

CH,O

HO

H

--

CH,O

q OH

9--

HO

CH30

CH30

OH

46

DAVID S . SEIGLER

genera Genista and Adenocarpus, which have long been considered related and both produce similar alkaloids. Four of the 15-20 species of Erythrophleum have been reported to contain alkaloids such as cassamine (89), representing one of the rare reports of alkaloids from the Caesalpinoidae (151, 152).

88

89

The alkaloids of the three subfamilies are derived from distinct biosynthetic pathways with the exception of certain simple amines which are widely distributed but primarily found in the subfamily Mimosoideae. Thus, alkaloid chemical data (and other chemical data such as the distribution of canavanine and certain nonmetabolic amino acids) support the separation of these three groups. Alkaloid data is less informative with respect t o the identification of possible ancestors of any of the three subfamilies but it is interesting in this regard that ~ r ~ t h r i nalkaloids a occur in the genus ~ r ~ ~ h r and i n aalso in certain members of the Menispermaceae and that many of the quinolizidine alkaloids found in the subfamily Lotoideae also occur in the Berberidaceae, Ranunculaceae, Papaveraceae, and Monimiaceae (all of the Magnoliidae) and only rarely in other sources (145, 153). Many of these records are in need of reexamination, as several of them are based on unvouchered plant materials and older chemical work. Further, the presence of numerous alkaloids derived from benzylisoquinoline pathways in the same plants suggests problems in identification of smaller amounts of cooccurring quinolizidine alkaloids. A few previous investigators (89-91) have considered the possibility that the Leguminosae are derived from a " ranunculalean-berberidalean " line on a basis of both chemical and morphological lines of evidence. Recent work by Boulter has shown that the amino acid sequence in cytochrome c from Phaseolus aureus Roxb. (Leguminosae, Lotoideae) and Nigella damascena L. (Ranunculaceae) are closely related (88). Alkaloid chemistry has been useful within the Leguminosae for the investigation of many problems a t the generic, specific, and infraspecific levels. Several of these have been reviewed by Mears and Mabry ( 1 5 , 2 2 ) .

1. PLANT SYSTEMATICS

47

6. The Euphorbiales

Cronquist ( 6 ) considers the family Euphorbiaceae (with about 7500 species) to be a member of the Euphorbiales, subclass Rosidae. The family is extraordinarily diverse in terms of both morphological and chemical characters and is of considerable economic importance. Qther workers have a t times placed the family in different orders. The Buxaceae (60 species), Daphniphyllaceae (35 species), and Aextoxicaceae (1 species), three other families of the order, were not considered closely allied to the Euphorbiaceae by Webster (154), while the Pandaceae (35 species) was thought to be related. Although the Euphorbiaceae contains many types of secondary plant compounds few of these are so widespread as to characterize the family. The principal exceptions are esters of phorbol(90) and other diterpenes which are found in genera belonging to several parts of the Euphorbiaceae as well as the Thymeliaceae [which Thorne places in his Euphorbiales, see Thorne (146)l (155-158). These compounds are apparently responsible for the irritating properties well known for members of this family.

90

R, = long, R, = short chain fatty acid

The alkaloids of the Euphorbiaceae have been reviewed by Hegnauer (153). Among these are compounds of the securinega type, such as securinine (91), which are widely distributed in two related genera, Securinega and Phyllanthus. It has recently been demonstrated that

91

48

DAVID 9. SEIQLER

these compounds are derived from L-tyrosine in a unique manner (159) in which tyrosine provides carbon atoms 6-13 of the securinine skeleton. The genera Hymenocaridia and Julocroton contain alkaloids, 92 and 93, respectively, that are based on polypeptide structures (153, 160). The genus Croton contains several benzylisoquinoline alkaloids, mostly of

NHC-CH(CH3)a

II

0 93

HN-H--CH(CH,),

II I

0 NH-G-CH-N(CH3)S

II I

0 CH(CH3)(Ca&) 92

the proaporphine type such as crotonsine (94). The genera Ricinus and Trewia contain two unusual alkaloids derived from nicotinic acid, respectively. Alchorneine (97), ricinine (95) and nudiflorine (W), alchorneinone (98), and other similar alkaloids have been isolated from AlchorneaJloribunda (161).These alkaloids appear to be of an imidazole

F

OCH, I

HO

CH3

I

NcrJo I

CH3

CH, 96

95

0

94

OMe

,OMe

97

1.

PLANT SYSTEMATICS

49

type. d-(3R, 6R )-3a-acetoxy-6/3-hydroxytropane, d-2a-benzoyloxy-3/3hydroxynortropane, and tropacocaine have been isolated from Peripentadenia mearsii (C. T. White) L. S. Smith (162). M,-Methyltetrahydroharman has recently been isolated from Spathiostemon javensis Blume ( =Homoroia riparia Lour.) and represents the first harman alkaloid from this family (163). A number of other alkaloid records in this family are questionable and should be reexamined. Among these are the presence of phyllalbine (a tropane type) in Phyllanthus discoideus Muell. Arg., 4-hydroxyhygrinic acid in Croton gabouga S. Moore, an ester of vasicine in Croton draco Schlecht., a bisbenzylisoquinoline alkaloid from Croton turumiquirensis Steyerm., yohimbine from Alchornea jloribunda Muell. Arg., and physostigmine from Hippomane mancinella L. [original references given in Hegnauer (153)]. Vouchering of plant materials is especially important in this group of plants, many of which are notoriously difficult to identify. Excluding these reports, the alkaloids of the Euphorbiaceae coincide reasonably well with the various subfamilial taxa although a large number of types are represented. Screening studies suggest that the Euphorbiaceae is still a source of unstudied alkaloids (123-123c, 1 6 3 ~ ) . The small family Pandaceae has recently been found to contain alkaloids such as 99, which closely resemble that of Hymenocaridia (Euphorbiaceae) and those of the Rhamnaceae (164) and Celastraceae (165).

99

The Daphniphyllaceae is a rather small family with 35-40 species, which most workers have considered to be related to the Euphorbiaceae (5, 6 ) . Webster (54),in accord with Hutchinson (142),would place the family in the Hamamelidae (sensu Cronquist). The chemistry of the family has been little studied with the exception of its unusual alkaloids. Some members of the family contain asperuloside, an iridoid monoterpene (Section V, B) ( 8 1 , 1 6 6 ) .Compounds of this type are not found in other families of the Euphorbiales (sensu Cronquist), nor are they

50

DAVID S. SEIGLER

commonly found in the Hamamelidae. They are, however, found in the Gentianales, Rubiales, Cornales, etc., which are discussed in Section V, B. The complex and unique alkaloids of this family, such as daphniphyllin (loo), have been shown to be of terpenoid origin. Six mevalonate units are involved in the synthesis of one alkaloid molecule (26, 167, 168).

100

Alkaloids which occur in the Buxaceae are derived from triterpenes and are discussed in Section V, B. I n summary, the Euphorbiaceae are rich in alkaloids of several major types. Two other families of the order that contain alkaloids, the Buxaceae and Daphniphyllaceae, do not appear to be closely related, while the third, the Pandaceae, produce alkaloids similar t o a t least one genus of the Euphorbiaceae. The Aextoxicaceae have apparently not been investigated. The ancestry of the Euphorbiaceae has long been in question. The family has been transferred from place to place although it has generally been considered close to the Geraniales or other orders of the Rosidae. Cronquist considers the Euphorbiales t o be descended from the Rosales (6), whereas Stebbins (12) did not consider the Rosales as necessary intermediates. The genus Croton contains benzylisoquinoline alkaloids. We should again ask the questions posed when we considered the origins of the Rutaceae: Did this family come from ancestors that synthesized benzylisoquinoline alkaloids, i.e., is it linearly descended from the Magnoliideae ; did benzylisoquinoline alkaloids arise independently in the family or did they come from a long line of intermediates in which synthesis of benzylisoquinoline alkaloids was “turned off” and in some proto-Euphorbiaceous ancestors was turned on again ‘2 7 . The Rhamnaceae and Celastraceae

The Rhamnaceae (Rhamnales) contain alkaloids of the benzylisoquinoline type as well as those with polypeptide skeletons; both of these types are found in the Euphorbiaceae. Cronquist ( 6 ) and other

1. PLANT SYSTEMATICS

51

workers have generally considered the orders Euphorbiales and Rhamnales to be somewhat related. Armepavine (101) has been isolated from Euonyrnus europaeus L. (Cefastraceae, order Celastrales) (165). Homoerythrina alkaloids, such as 102, have recently been reported from the genus Phelline of the Aquifoliaceae (73, 7 4 ) . Macrocyclic peptides have also been isolated from this species, further establishing the probability of close relationship between the Euphorbiales, Celastrales, and Rhamnales (165).

~~~02 CH30,

HO

HO

CH,O

CH3

-

/ 102

101

Bhesa archboldiana (Merrill and Perry) Ding Hou has recently been reported to contain 9-angelylretronecine, its N-oxide, and calycanthine (169). The same questions as were asked about the ancestry of the Euphorbiaceae apply to the Rhamnaceae and Celastraceae. 8. Alkaloids in the Erythroxylaceae

Cronquist considers the Erythroxylaceae (Subclass Rosidae) to be related to the Linaceae, as have most other authors (6). The family is quite small (about 200 species), and many species contain alkaloids that are known for their physiological properties, such as cocaine (103), as well as other alkaloids derived from ornithine via pyrrolidine intermediates and from lysine (e.g. hygrine, pseudotropine, and anabasine). Neither of the two families (Linaceae or Humiriaceae) of the order Linales contain alkaloids, nor do plants of the Geraniales in which this family has also been placed. One must almost certainly conclude ,CH3

Nb CO,CH,

H

103

OCOC,H,

52

DAVID S. SEIGLER

that the alkaloids of this family represent a case of independent evolution of tropane-type alkaloids. 9. Alkaloids with Monoterpene Sesquiterpene and Diterpene Skeletons

A number of monoterpenoid compounds, such as nepetalactone (104) of the iridoid group (49-53,93,94,170),incorporate nitrogen to produce alkaloids such as actinidine (105).These compounds are found in several plant families; among them are the Gentianaceae, Apocynaceae, Actinidiaceae, Bignoniaceae, Loganiaceae, Orobanchaceae, Menyanthaceae, Plantaginaceae, Oleaceae, Scrophulariaceae, Valerianaceae, and Dipsacaceae (49-52,lrOa).One of these compounds, gentianine, has been shown to be an artifact of isolation under certain conditions.

104

105

The parent terpenoids have wide distribution. They occur in ants of the genus Iridomyrmex and in many plants, primarily as the glycosides. Several aspects of the biosynthesis, distribution, and chemotaxonomy . of of this group of compounds have been reviewed ( 8 1 , 1 6 6 , 1 7 1 ) Many the families in which they occur are in the Asteridae and Rosidae (sensu Cronquist) and the presence of iridoid monoterpenes and the monoterpene alkaloids (Table I) appears to demonstrate several relationships within the group. For example, the presence of these compounds suggests a close relationship between the Actinidiaceae (order Theales) and the Pyrolaceae and Ericaceae (order Ericales), all of the subclass Dilleniidae. The presence of iridoid compounds in these three families is anomalous in the subclass. Investigations of plant taxa for the presence of both iridoids and the corresponding glycosides appears to be a fertile area to provide additional information for the placement of several families. 10. Alkaloids Derived from Tryptophan That Contain a Monoterpenoid Moiety

A large number of alkaloids that are important medicinally are derived by union of simple amines derived from tryptophan and an iridoid monoterpene unit. These are commonly known as the indole

1. PLANT SYSTEMATICS

53

TABLE I FAMILIES THAT

CONTAIN

IRIDOID COMPOUNDS

Rosidae Escalloniaceae Daphniphyllaceae , Fouquieriaceae Cornaceae Garryaceae Hippuridaceae Hydrangeaceae (Hydrangea) Alangiaceae

Hamemelidae Eucommiaceae Hamamelidaceae (Liquidambar)

Dilleniidae Ac tinidaceae Ericaceae Proteaceae

As teridae Rubiaceae Scrophulariaceae Orobanchiaceae Globulariaceae Plantaginaceae Buddlejaceae Lentibulariaceae Apocynaceae Verbenaceae Martyniaceae Callitrichaceae Acanthaceae Dipsacaceae Pedaliaceae Labiatae Myoporaceae

alkaloids. The biosynthesis of simple amines derived from tryptophan and condensation of these units to produce Calycanthus alkaloids has previously been mentioned and the distribution of both iridoid monoterpenes and the corresponding monoterpene alkaloids has been summarized (Section V, B). Loganin (106), a precursor of most indole alkaloids, as well as of emetine alkaloids, is found in several families; among them are the HO 0-glucosyl CH30.C

CH3O.C 106

107

Apocynaceae, Loganiaceae, Meyanthaceae, and several Lonicera species (Caprifoliaceae) (171). The corresponding acid, loganic acid is found in the Gentianaceae, Apocynaceae, Alangiaceae, and Loganiaceae (119). Loganin is converted in certain plants to secologanin (107)) which is a more immediate precursor of indole and emetine alkaloids.

54

DAVID S. SEIOLER

Relatively unchanged addition products of tryptophan and secologanin u n i t s such as cordifoline (108) are found in Adina cordifolia Hook. of the Rubiaceae.

108

The corresponding decarboxylated compound strictosidine (109) has been found in Rhazya and Catharanthus species of the Apocynaceae, although the compound with opposite configuration a t C = 3 has not been isolated from the higher plants.

109

The route(s) from intermediates of the above type to the various types of indole alkaloids has been the subject of much speculation (171). Among the types observed are ajmalacine (110) and its relatives (Corynanthe type), stemmadinine types (lll),Aspidosperma types, such as tabersonine (112),Iboga types such as catharanthine (113),and Xtrychnos types such as strychnine (114). Several other basic skeletons are known, and the relation of many of these to the preceding types is enigmatic.

111

1.

55

PLANT SYSTEMATICS

113

112

114

Indole alkaloids are found in several families-the Nyssaceae, (Camptotheca acuminata Decne.), Icacinaceae, (Nappia foetidu Miers and Cassinopsis ilicifolia Kuntze), Alangiaceae, Loganiaceae, Apocynaceae, and Rubiaceae (49-52, 172-224). The families Nyssasaceae (8 species) and Alangiaceae (18 species) are members of subclass Rosidae order Cornales, whereas the families Icacinaceae (400 species) is a member of the order Celastrales. Other workers (225, 226) consider the Icacinaceae to be more closely related to the former two families. There is both chemical and morphological unity among the families Gentianaceae (1100 species), Menyanthaceae (40 species) (which Cronquist places in the order Polemoniales, subclass Asteridae), Loganiaceae (500 species), Apocynaceae (2000 species), Asclepiadaceae (2000 species), and Rubiaceae (6000-7000 species). All except the Asclepiadaceae contain precursors of the indole alkaloids if not the alkaloids themselves (e.g., the Gentianaceae and Menyanthaceae). The complex pathways leading to these compounds preclude independent evolutionary origin of the indole alkaloids they contain. The Apocynaceae has been divided into three subfamilies by Pinchon [see complete series of references in Hegnauer (78j.l Of these, the Plumerioideae contains indole alkaloids, the Cerberoideae monoterpene alkaloids, and the Echitoideae steroidal alkaloids (78).Problems a t the genus and species level have been extensively investigated in this family because of the medicinal importance of the alkaloids; several of these studies have been reviewed (18, 25, 145, 153, 186, 190-201, 204-212, 227, 228).

56

DAVID S . SEIGLER

The families Apocynaceae and Asclepiadaceae are closely related from a morphological view. Some authors have suggested that the two families intergrade and the line between the two is arbitrarily established ( 6 ) .Interestingly, alkaloid chemical data for the two families is distinct, although many of the intergrading taxa need to be examined. The family Apocynaceae is quite rich in indole alkaloids, whereas most species of the Asclepiadaceae are devoid of them, and the few that do contain alkaloids, mainly the woody genus Tylophora and members of the genus Cynanchum (or Vincetoxicum), contain compounds such as Z-tylophorine (115), which are derived from phenylalanine (and ornithine). Alkaloids of this type have also been reported from members of

OCHB 115

the Moraceae and Lauraceae (229-231), although some of these reports should be confirmed. Thus, the Asclepiadaceae appear to be a family that has either lost the ability to synthesize indole alkaloids or possibly is an example of a group with “dormant” pathways that may be reactivated a t some time in the future. The Loganiaceae has traditionally been segregated into six tribes; Hutchinson elevated these to five families in his Loganiales (142).Indole alkaloids are widespread in the tribes Gelsemiae and Strychneae; two of the other tribes have been little investigated. Another family, Buddlejaceae, has often been placed near or combined with the Loganiaceae; Cronquist places it in his Scrophulariales. Several species of the family contain alkaloids (123-123c, 163a), but no specific compounds have been characterized. Investigation of these alkaloids could provide useful information for the taxonomic placement of the family. The Rubiaceae (order Rubiales, subclass Asteridae) synthesize many indole alkaloids as well as compounds such as emetine (116), which are derived from similar pathways but with a dopamine instead of a tryptamine precursor and quinine (117) from extensive rearrangement

57

1. PLANT SYSTEMATICS

CH30,C

,A&

HN-' 116

117

of indole alkaloid precursors. The former (emetine type) are restricted t o the Rubiaceae and occur in several genera, among them Cephaelis and Psychotria. Quinine and closely related compounds are found in the genera Cinchona, Remija, Contarea, and Ladenbergia of the Rubiaceae. However, by far the most common alkaloids in the Rubiaceae are those that are identical with or derived from those found in the Apocynaceae and Loganiaceae. There is little question that the Rubiaceae must have been derived from common ancestors of the Gentianales or from members of the Gentianales. Did the families of the Asteridae that contain iridoid compounds and their derivatives come from families of the Rosidae that are iridoid containing (i.e., the Rosales) as Cronquist suggests? Or have these been derived from " Saxifragalean and Cornalean ancestors as other authors suggest (89-91) !' The same possibilities of independent origin, dormant biosynthetic mechanisms, or linear descent rise again. )'

11. Alkaloids with Sesquiterpene Structures

Alkaloids with sesquiterpene skeletons are unusual in nature (49-52, 232,233) but are known to occur in the Nympheaceae (see the discussion of alkaloids in the Magnoliales). Both Nymphaea and Nuphar contain compounds such as 118 (26, 232, 233).

58

DAVID S. SEIQLER

118

The alkaloids of Nuphar and Xymphaea are not found in the Nelumbonaceae, nor are those of Nelumbo found in other families of the order. A clear dichotomy exists between the groups from both morphological and chemical grounds suggesting that the two groups are not closely related. 12. Alkaloids with Diterpene Structures

Alkaloids with modified diterpene structures occur in the Garryaceae (5 species)(order Cornales, subclass Rosidae), the genera Aconitum and Delphinum of the Ranunculaceae (order Ranunculales, subclass Magnoliidae), in Inula royleana DC. (order Asterales, subclass Asteridae), and Spiraea japonica L. (order Rosales, subclass Rosidae) (49-52, 78, 81). Many of these compounds are intensely poisonous and some are among the most toxic materials of plant origin known t o man. Several are used medicinally. These compounds may be divided into two broad categories. The first of these includes a series of relatively simple amino alcohols that are modeled on a C-20 skeleton, and the second group is more highly substituted and frequently based on a C-19 skeleton (234-239). These alkaloids arise from tetra- or pentacyclic diterpenes in which atoms 19 and 20 are linked with the nitrogen of a molecule of /3-aminoethanol, methylamine, or ethylamine t o form a heterocyclic ring (236).Pour basic skeletons of diterpene alkaloids are known. The veatchine skeleton, e.g., veatchine (119),which occurs in the genera Garrya (Garryaceae) and Aconitum (Ranunculaceae), is based on a kaurane skeleton (120) and obeys the isoprene rule. The other three skeletons, the atisine, lycoctonine, and heteratisine types,

€19

59

1. PLANT S Y S T E M A l T C S

do not obey the isoprene rule and are found in both Aconitum and Delphinium species. Compounds such as atisine (121),Iyeoctinine (122), and heteratisine (123) are respective representatives of these groups. The latter two types are based on a C-19 skeleton. Alkaloids from Inula

120

121

OH 122

123

royleana (Compositae) are identical with certain alkaloids of the lycoctonine type which occur in the genus Aconitum ('78),whereas those from Spiraea (Rosaceae) (e.g., 124) represent a unique type. It is difficult to assess the taxonomic significance of these alkaloids. The kaurane series of diterpenes also give rise t o gibberellins, which are

OH 124

found in most if not all higher plants. The number of changes necessary t o produce compounds such as veatchine from these intermediates may be less than would appear on casual observation. No doubt many more changes are required to produce more complex diterpene alkaloid types. The Garryaceae are probably not closely related to the Ranunculaceae and neither are particularly close t o the Compositae.

60

DAVID S. SEIGLER

13. Alkaloids Containing Steroidal or Triterpenoid Nuclei

Several plant families produce alkaloids that are biosynthesized from steroids (240-249). The genera Holarrhena, Funtinnia, and Malonetia of the Apocynaceae and Sarcocca and Pachysandra of the Buxaceae produce alkaloids based on the 5-a-pregnane skeleton. Cholesterol has been suggested as an intermediate in the synthesis of steroidal alkaloids such as holophyllamine (125) and conessine (126) in species of Holarrhena (53). CH,

125

126

The family Solanaceae is widely known for its diverse and plentiful alkaloid content. The genera Solanum and Lycopersicon (and others) contain steroidal alkaloids that are similar in structure t o the steroidal saponins they possess. Many of these compounds have complex. di- and trisaccharide moieties. Alkaloids of this type, such as solanidine (127) and solanocapsine (128), indicate a close relationship between these alkaloids and cholesterol.

'r

HO'

H 127

128

The structures of several C-nor-D-homosteroids from the genus Veratrum of the Liliaceae will be discussed in Section V, C. Several members of the Buxaceae (Euphorbiales sensu Cronquist) contain exceedingly complex mixtures of alkaloids (250).Most of these alkaloids have substitution patterns that resemble triterpenes but do not possess the typical C- 17 side chain. Several possess cyclopropane rings reminiscent of cycloartenol, such as cyclobuxine-D (129), whereas others, such as buxenine-G (130), have a ring expanded system.

1. PLANT SYSTEMATICS

129

61

130

Buxus alkaloids are not known from other plant groups, although they are widespread in the family. Webster (154) does not feel that the Buxaceae is closely related to the Euphorbiaceae; the two families have few chemical characters in common (78). Hutchinson (142) suggested the family was in the Hamamelidales, but there is little chemical evidence to confirm or deny this placement. 14. The Solanaceae

The Solanaceae is one of the richest families with regard to the absolute number of species that contain alkaloids. Cronquist places the Solanaceae in the order Polemoniales of the Asteridae ( 6 ) .It is the largest family in the order with about 2300 species (about 1700 of these in the genus Solanum) followed by the Convolvulaceae with about 1400. While the Solanaceae are extremely rich in alkaloids, few are found in other families of the order. Pyrrolidine and tropine types have been reported from the genus Convolvulus and ergot alkaloids (Section v, B) are present in the Convolvulaceae (49-52, 5 6 5 5 ) . A large number of genera of the Solanaceae contain alkaloids derived from ornithine via pyrrolizidine intermediates (Table 11) (53, 93, 94). The biosynthesis of these alkaloids has been previously discussed TABLE I1 GENERAOF

THE

SOLANACEAE THAT CONTAIN ALKALOIDS DERIVED FROM ORNITHINEAND LYSINE

Atropa Hyoscyamw Physochlaina Datura Duboisia Latura Mandragora Scopolia

Solanum Solandra Physalis Anisodus Nieandra Methysticodendron Withania Nicotiana

Brugmansia Salpiglossis Salpichroa Streptosolen Dunalia Cyphomandra Anthoeereis

62

DAVID S. SEIGLER

(Section 111, B). These plants are distributed in all five subfamilies of the family as seen by Wettstein (78).Nicotine and anabasine are found in several genera that contain other ornithine- and lysine-derived compounds (e.g., Duboisia, Nicotiana, Withania, and Salpiglossis). The distribution of certain steroidal glycosides with skeletons such as 131 below has been reviewed by Lavie (251). This group of chemists studied the complex inheritance patterns of these compounds in several genera- Withania, Physalis, Jaborosa, Nicandra, and Acnistus.

'.

Steroidal alkaloids of these and other types are widely distributed through the family (Table 111) and parallel the presence of steroidal glycosides in the family. The genus Solanum is noted for the types of both steroidal glycosides and alkaloids that it contains. Similar compounds are also found in the genus Veratrum of the Liliaceae (Section

v, C).

15. Ergot Alkaloids

This group of indole alkaloids is found in members of the fungal genus Claviceps, especially Claviceps purpurea (Fries) Tul. (an obligate parasite of rye), and in certain members of the angiospermous family Convolvulaceae (49-52, 78, 81). Compounds of this type, e.g., agroTABLE I11 GENERAOF THE SOLANACEAE THAT CONTAINSTEROIDAL ALKALOIDS Lycopersicon Solanum Cestrum Cyphomandra

Capsicum Physochlaina Scopolia Withania

1.

63

PLANT SYSTEMATICS

132

clavine (132),arise by condensation of tryptophan and mevalonate units and subsequent cyclization (27,53,93,94,216,220,221,252). Alkaloids of the clavine series are found in both Claviceps and in the genera Rivea and Ipomoea of the Convolvulaceae. In certain alkaloid-producing strains of ergot, agroclavine (132) is converted to elymocIavine (133), which serves as a precursor for lysergic acid (134) and other related

132

133

compounds. Ergine (lysergic acid amide) (135) and erginine (isolysergic acid amide (136) have been isolated from hydrolyzates of Rivea corymbosa (L.)Hall. f. and Ipomoea tricolor Cav., which were used by Mexican indians as a drug under the name ololiuqui (221, 253). The majority of alkaloids from ergot are peptides of lysergic acid. The therapeutically most important ergot alkaloids are of this type. There is no question of close relationship between Claviceps (an Ascomycete) and the Convolvulaceae (an angiosperm from an evolutionarily

134

135

136

64

DAVID S. SEIGLER

advanced family). The pathways leading to both clavine and lysergic acid types appear to be identical in both groups, precluding origin by different pathways or at best making it very unlikely. Alkaloids of the complexity of ergot types are seldom encountered among fungi (7’8) and are otherwise unknown from the Convolvulaceae (49-52, 78, 81). Did these pathways evolve independently and against statistical odds in the two groups! Another possibility is suggested by Went ( 3 6 ) in his discussion of parallel (convergent 1 ) evolution in which he discusses the possibility that genetic units have been transferred from organism to organism by the action of viruses or other parasitic forms of life. It is known that viruses are capable of transferring genetic material between certain strains or species of bacteria ( I ) , but this process has not been established for more highly evolved organisms. Although most of Went’s examples can be more easily explained by other mechanisms (such as natural selection acting upon a highly variable gene pool) one cannot discount the possibility of such transfers in cases such as ergot alkaloid synthesis. 16. Miscellaneous Alkaloids and Families

a. Tylophorine and Related Types of Alkaloids. Alkaloids of this general type have been isolated from the Asclepiadaceae (Tylophoraand Cynanchum or Vincetoxicum),the Lauraceae (Cryptocarya), the Urticaceae (Boehmeria platyphylba and B. cylindrica) (254, 254a), and the Moraceae (Ficus). Tylophorine (115) alkaloids in the Asclepiadaceae have been suggested t o arise from condensation of a phenylalanine and an ornithine unit and subsequent union of a unit of tyrosine (2543).The biosynthesis of cryptospermine (74) type alkaloids has not been investigated. It is generally conceded that the Moraceae and Urticaceae are closely related, but the other two families are quite distant. b , The Elaeocarpaceae. The family Elaecarpaceae contains a unique type of alkaloid such as d-isoelaeocarpicine (137)(255).Alkaloids are otherwise rarely reported in the Malvales. C . The Cruciferae. Several nitrogen-containing compounds have been H

137

1. PLANT SYSTEMATICS

65

isolated from this family, most of which are related to the glucosinolates which are widespread in the family, although several (e.g., 138),mainly those from the genus Lunaria appear to be of a unique type (78,81,256).

138

C. THE LILIOPSIDA(MONOCOTYLEDONOUS PLANTS) Alkaloids among the monocotyledonous plants are, with the exception of simple amines, mostly found in families of the Liliales and the Orchidales, although a few are known to occur in other families. Liriodenine, lysicanine (139), and nuciferine have been reported

CH,O

139

from Lysichitum camtschatcense Schott. var. japonicum Makino of the Araceae (order Arales, subclass Arecidae) (257).Several simple alkaloids, such as arecoline (140), are found in the Palmae (order Arecales, subclass Arecidae). A number of simple amines, e.g., hordenine (12), candicine, tyramine, and N-methyltyramine, are widely distributed in the Gramineae (49). More complex alkaloids such as festucine (142) and loline (143), pyrrolizidine alkaloids that occur free in nature, have been

CH, 140

141

66

DAVID S. SEIGLER

HNCH,

142

143

found in the genera Festuca and Lolium, respectively. Perlolyrine (144) has also been isolated from the genus Lolium (258). Most alkaloids of the monocotyledonous plants are concentrated in the Liliidae, especially in the order Liliales, but also in the Orchidales.

CH,OH 144

Alkaloids commonly found in the Liliaceae (including the Amaryllidaceae) are derived from phenylalanine and/or tyrosine but differ in structure from types found in dicotyledonous plants. Alkaloids in the Orchidaceae are mostly restricted t o several genera of that family and are of an unusual type. 1. The Liliales

The Liliales, as defined by Cronquist, comprise 13 families and nearly 7700 species. He combines the Liliaceae and Amaryllidaceae to produce the largest family of the order, the Liliaceae, which has about 4200 species. Other families in the order are the Iridaceae (1500 species), Dioscoreaceae (650 species), Agavaceae (550 species), Smilacaceae (300 species), Velloziaceae (200 species), Haemodoraceae (1 20 species), Xanthorrhoeaceae (50 species), Pontederiaceae (30 species), Stemonaceae (30 species), Taccaceae (30 species), Philydraceae ( 5 species), and Cyanastraceae (5 species). Of these, alkaloids are known from the

Liliaceae (from members of both the former Liliaceae and Amaryllidaceae), Dioscoreaceae, and Stemonaceae (49-52). The Liliaceae and Amaryllidaceae were traditionally separated from one another by the single character of position of the ovary-inferior in Amaryllidaceae and superior in the Liliaceae ( 6 ) . This difference is now not considered so significant with separation of the Agavaceae from this group, and Cronquist says that it appears the traditional

1.

PLANT SYSTEMATICS

67

COMMELINIDAE

FIG.2. Subclasses of Liliopsida according to Cronquist (6).

Amaryllidaceae were really several different groups that had independently become epigynous. Steroidal glycosides are widespread among species of the Liliaceae, Agavaceae, and Dioscoreaceae, but are not found in the Amaryllidaceae (78, 81). The Amaryllidaceae alkaloids comprise a unique group of bases that have so far been found only in that family (49-52,259-261). Conversely, with the exception of hordenine, alkaloids of other plant families have not been found in the Amaryllidaceae. Three major pathways of alkaloid biosynthesis in this family arise from the compound norbelladine (145), which is derived from one molecule of tyrosine and one molecule of phenylalanine. One of these pathways gives rise to lycorine

dOH

HO+&H,NHCH. 145

(146) and its congeners via Scheme 3. A second gives rise to haemanthamine (147), pretazettine (148), and tazettine (149) via Scheme 4. The third pathway gives rise to compounds such as narwedine (150) and galanthamine (151) via Scheme 5. All three pathways are present in many genera of the family (49-52, 7 4 , 78, 81) and in most of the tribes of the Amaryllidaceae according to Hutchinson (78).Other subfamilies, a number of which were raised to the rank of family by Hutchinson, do not have these alkaloids (142). In some members of the Liliaceae, one molecule of phenylalanine and one molecule of tyrosine unite to form series of compounds such as colchicine (152) and androcymbine (153).

68

DAVID 5. SEIGLER

Norbelladine --+

OH

CH30

CH.0

++ HO 146

SCHEME 3

147

HO

149

148

SCHEME 4

150

CH,O .*-

151

SCHEME 5

69

1. PLANT SYSTEMATICS

‘ CH,O

\

OCH,

0

Hutchinson (142)divided the Liliaceae into 28 tribes and a t the same time elevated a number of groups previously placed in the Liliaceae to familial level (78).Of these 28 tribes, the Uvularieae, Anguillarieae, and Colchiceae contain colchicine and related alkaloids. These alkaloids are present in the genera Androcymbium, Colchicum, Gloriosa, Littorica, Merendera, Camptorrhiza, Kreysigia, Dipidax, and Iphigenia but absent from many others from which related alkaloids have been reported (262-265). The Veratreae, a related tribe, contain many alkaloids that are derived from steroidal precursors such as cholestanol as well as those of the C-nor-D-homo type (78,247-250). These extremely toxic compounds are found throughout the genera Veratrum, Schoenocaulon, and Zygadenus and are similar to those found in the Solanaceae, Buxaceae, and Apocynaceae. An example of the former type is veralkamine (154). H

154

The genus Fritillaria of the subfamily Lilioideae contains alkaloids that are similar in structure to those of the Veratreae. The similarity in alkaloids and in certain lactones leads Hegnauer (78) to suggest a relationship between the two groups. Others have previously considered the Lilioideae to be derived from members of the Melanthioideae (265). The Dioscoreaceae is best known for the steroid glycosides its species contain. These are similar in structure to those found in the Liliaceae, Agavaceae, and certain allied groups. I n contrast to the Liliaceae, however, the Dioscoreaceae contain alkaloids based on a quinuclidine structure such as 155 (49-52, 78). It has now been demonstrated that four acetate units are condensed with a lysine derived piperidine unit to

70

DAVID S. SEIGLER

yield Dioscorea alkaloids (266).To date these have only been found in African and Asian species of the genus, and interestingly, those with alkaloids were found to be practically free of saponins (78). Earlier reports of tropane alkaloids in this family are probably erroneous.

155

The Stemonaceae, a small family of three genera (4,have been shown to contain approximately fourteen alkaloids of a unique type such as tuberostemonine (156).

156

Cronquist views the families of the Liliales as being derived from the Liliaceae, with the exception of the Philydraceae and Pontederiaceae. He further views the Amaryllidaceae as several groups of the Liliaceae that had independently become epigynous. The Dioscoreaceae and Stemonaceae are broadleaf climbers that are also derived from Liliaceous parents. The Iridaceae are much like the Liliaceae in that they frequently exploit the bulbous and cormose habit, but they have not been reported to contain alkaloids. I n summary, alkaloid chemistry suggests that the Liliaceae and several groups of the Amaryllidaceae are distinct. The Dioscoreaceae and Stemonaceae contain alkaloids not found in either and do not contain alkaloids of the type found in the Liliaceae-Amaryllidaceae. 2. The Orchidaceae

This large family with approximately 20,000 species has been little investigated chemically but is known to contain alkaloids derived from ornithine. Appropriate alkylation of a pyrrolidine intermediate with an acetate- andfor propionate-derived precursor gives compounds such

1. PLANT SYSTEMATICS

71

as crepidine (157), which are known principally from the genus Dendrobium but also from other genera which have been summarized (78, 81, 267-269). Simpler compounds such as hygrine (16) have also been

I

157

reported from several genera and add credence to the proposed biosynthesis of more complex alkaloids by the internal alkylation of a pyrrolidine moiety. Pyrrolizidine types such as 158 from the genus Lipuris and Mu&xis are also known.

R'

various R and R' substituents

158

The differences between major groups of orchids have few absolute distinctions and several taxonomic schemes have been proposed, for example, those by Garay (270), Dressler and Dodson (271), and Airy-Shaw (140).Most alkaloid-containing species are concentrated in the group Epidendreae and especially in the genus Dendrobium. Cronquist views the Orchidaceae as being derived from the Liliales, probably from Amaryllidaceous ancestors. The alkaloids of this giant family do not resemble those of the Lilales, nor do the Orchidaceae contain alkaloids of the types found in either the Amaryllidaceae, the Liliaceae, or other extant families of the Liliales. 3. Alkaloid Chemical Data and the Origin of the Monocotyledonous

Plants

Bessey (272) and several other systematists proposed that the monocotyledonous plants arose from plants similar to the Ranunculales and that primitive monocots resembled the Alismatales. Cronquist ( 6 )

72

DAVID S. SEIGLER

discards this theory and derives them from the Nympheales of his Magnoliidae, primarily on a basis of resemblance of extant members of the Nympheales (especially Nymphuea and Nuphur), to a model he proposes for a primitive monocotyledonous plant. Stebbins (12) rejected this hypothesis as well as that of Bessey, as he felt many of the characters used by both of the previous investigators were secondarily derived rather than primitive. He further states that no modern orders of either monocotyledonous or dicotyledonous plants are derived from extant ancestors and suggests that monocots are derived from ancestors similar to Drirnys (Winteraceae, subclass Magnoliidae). Chemical data do not clearly resolve problems related to the origin of monocots. Alkaloids of the monocots are different from those of the dicots. I n only a few cases similar compounds are produced, e.g., some amaryllidaceous alkaloids resemble those derived from benzylisoquinoline precursors, certain orchidaceous alkaloids resemble those derived from ornithine in dicots, and steroidal alkaloids of the Liliaceae resemble those of the Solanaceae, Apocynaceae, and Buxaceae. Several simple amines (tyramine, gramine, tryptamine, candicine, etc.) do occur in monocots and dicots, but as previously discussed these are rarely significant a t higher taxonomic ranks. If the proposals of either Bessey or Cronquist are correct it is necessary to derive the monocots from non-alkaloid-containing lines or to suppose that the ability to synthesize either benzylisoquinoline alkaloids of advanced types (as occur in the Ranunculales) or sesquiterpene alkaloids (as occur in the Nympheales) has been lost. From extant data for the distribution of alkaloids in monocots it is clear that most primitive monocots (as discerned by either the system of Bessey or Cronquist) are devoid of alkaloids, and alkaloid synthesis as seen in monocots, e.g., the Liliales, must be independently derived. Cronquist suggests that the Winteraceae is one of the families ancestral to other families of the order Magnoliales. It is interesting that no benzylisoquinoline alkaloids have been isolated and characterized from this family. On the other hand, benzylisoquinoline alkaloids have been reported from a t least one monocot, a member of the Arales (257), although with apparently unvouchered plant materials. This record should be reexamined since it represents a most important occurrence for studies of phylogeny and origin of this group. Studies of the amino acid sequences of cytochrome c by Boulter (88) indicate that monophyletic origin of the monocots from dicotyledonous lines is probable. It also appears from this evidence that both the monocotyledonous and magnolidean lines diverged after those of the Caryophyllales and thus the flower and chemistry of truly primitive angiospermous plant may resemble that proposed by Meeuse (89-91) rather than the Ranalean type, which has become widely accepted.

1.

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