A chemotaxonomic study of diterpenes from marine brown algae of the genus Dictyota

The Science of the Total Environment, 75 (1988) 271-283 Elsevier Science Publishers B.V., Amsterdam -- Printed in The Netherlands

271

A C H E M O T A X O N O M I C S T U D Y OF D I T E R P E N E S F R O M M A R I N E B R O W N A L G A E OF THE G E N U S D I C T Y O T A

VALERIA L. TEIXEIRA Laboratorio de Botanica Marinha, Faculdade de Biologia e Psicologia maria Thereza, Rua Viscone do Rio Branco 869, 24, 020 Niteroi, RJ (Brazil)

ALPHONSE KELECOM Laboratory of Marine Natural Products, Departamento de Biologia Geral, Universidade Federal Fluminense (UFF), C.P. 100.183, 24.000 Niteroi, RJ (Brazil)

ABSTRACT Diterpenes from Dictyota species appear to be valuable taxonomic markers and showed, for various species, strong correlation with botanic data. Our results corroborate the Theory of Micromolecular Evolution that states that higher oxidation levels, in a given taxon, are characteristic of evolutionarily more advanced components.

INTRODUCTION P h a e o p h y t a are b r o w n algae, a l m o s t exclusively marine, litophylic, occasionally epiphytic, and found p r i n c i p a l l y in cold and t e m p e r a t e w a t e r s [1]. The division P h a e o p h y t a possesses one single class, P h a e o p h y c e a e , composed of a b o u t 250 g e n e r a and m o r e t h a n 1500 species [2]. A c c o r d i n g to W y n n e and L o i s e a u x [3], P h a e o p h y c e a e are d i s t r i b u t e d in 13 orders, two of which, F u c a l e s and Dictyotales, are p r e d o m i n a n t in t r o p i c a l and sub-tropical seas [2]. The o r d e r D i c t y o t a l e s includes 16 fully defined g e n e r a [4]. A m o n g these, the g e n e r a Dictyota L a m o u r o u x , D i l o p h u s J. Agardh, Glassophora J. Agardh, P a c h y d i c t y o n J. Agardh, S p a t o g l o s s u m K u t z i n g and S t o e c h o s p e r m u m K u t z i n g p r o d u c e a series of d i t e r p e n e s t h a t are p r o b a b l y involved in h e r b i v o r y c o n t r o l [5, 6]. T h e genus Dictyota, with some 30 species, has been c h e m i c a l l y the most e x t e n s i v e l y investigated: m o r e t h a n 90 d i t e r p e n e s of 17 skeletal classes h a v e been isolated from 18 species d i s t r i b u t e d in all the o c e a n s [7]. Since problems still exist in establishing the s e p a r a t i o n limits b e t w e e n species and v a r i e t i e s of v a r i o u s Dictyota r e p r e s e n t a t i v e s [8, 9], it has been suggested t h a t the algae d i t e r p e n e s m i g h t be of c h e m o t a x o n o m i c i n t e r e s t [10-12]. H o w e v e r , t h e r e h a v e been no t a x o n o m i c n o r p h y l o g e n e t i c i n f e r e n c e s from the c h e m i c a l d a t a r e s u l t i n g from the i s o l a t i o n and identification of d i t e r p e n e s from Dictyota species. It is the aim of this w o r k to i l l u s t r a t e the g r e a t p o t e n t i a l of Dictyota d i t e r p e n e s as c h e m o t a x o n o m i c and p h y l o g e n e t i c markers.

272 METHODOLOGY Usually, chemosystematic studies are based on a presence/absence record of metabolites [13]. It cannot be over emphasized, however, that such a criterion may not be considered as fully reliable for chemotaxonomic purposes for at least two reasons. First, because the presence of metabolites in an organism may have been overlooked, and second because the isolation of known compounds, even from new sources, is generally not reported (and even not accepted for publication) in the main journals. Consequently, compounds that are in fact present will be considered absent, and this may obviously alter the chemotaxonomic conclusions. Hence, a methodology t h a t is not based on a presence/absence criterion is necessary for the use of natural products in taxonomy. Such a tool has been devised by O.R. Gottlieb [14] and has been extensively used for this study. Accordingly, all diterpenes isolated from Dictyota species up to June 1986 have been characterized by two indexes. First, the skeleton specialization index (SI), calculated from the theoretical number of steps, involving C-C bond formation or cleavage, that are necessary to derive a particular skeleton from the common geranyl-geraniol precursor (see Figs 1-3). Second, the oxidation index (OI), which considers identical all compounds having the same molecular formulae and functionality irrespective of the isomer. Each Dictyota species was then characterized by the skeletal evolutionary advancement index (EAs) and by the mean oxidation index (OI), both obtained as the arithmetic mean respectively of the SI and OI values of each diterpene isolated from considered species. For a detailed description of the methodology, see Gottlieb [14]. RESULTS The 17 diterpene skeletons obtained from Dictyota species are shown in Figs 1-3, and the number of diterpenes of each skeletal class is reported in Table 1. The unidentified species for which chemical data are available were arbitrarily numbered, in order to allow further discussion. Based on a revised biogenetic scheme proposed by the present authors in an earlier study [7], the diterpenes have been distributed into three groups (I-III), depending on the first formal cyclization of the geranyl-geraniol precursor. Diterpenes of Group I are mainly prenylated derivatives of known sesquiterpene skeletons t h a t result from a first cyclization of geranyl-geraniol between positions 1 and 10 (Fig. 1). Group II contains diterpenes derived by a cyclization of the precursor between positions 1 and 11 (Fig. 2). With the exception of the dolabellane skeleton, the diterpene skeletons of this group are restricted, among Dictyotales, to Groups I and III. Whether or not D. spinulosa, for which only one xeniane-related diterpene had been reported [12], belongs to the latter group will be discussed later. Finally, the cosmopolite D. dichotoma [2], which is considered to be the type species of the genus [4], is the only species that produced diterpenes from all three groups [13-55]. Our results, obtained by numerical treatment using the mean oxidation (OI)

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and the mean skeletal evolutive advancement (EAs) indexes for all the Dictyota species considered in this work, are reported in Fig. 4. The A area includes species that yield exclusively diterpenes from Group I. These are characterized by low OI (~ - 1.43) and EAs (~ 0.10) values. Dictyota masonii was tentatively included (dotted line) in sub-group A for having only one diterpene reported [19] whose OI and EAs indexes (OI = - 1 . 5 0 ; EAs = 0.05) were found to be in discrepancy with the values observed for the other species of sub-group A. Sub-group B corresponds to species that produce diterpenes belonging exclusively to Group II. Their main characteristics are high OI (~ 1.26) and EAs (~ 0.15) values. Among these species, Dictyota sp 1 is peculiar in being the

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only one that afforded dolabellanes, when all the other species yielded dolastanes. Sub-group C includes the algae that furnish diterpenes from Groups I and III. T h i s s u b - g r o u p is c h a r a c t e r i z e d by t h e l o w e s t E A s v a l u e ( ~ 0.09) a n d by a n OI v a l u e of - 1.32. In t h i s s u b - g r o u p , Dictyota prolificans is d i s c r e p a n t for h a v i n g

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277 a high OI value ( - 1.07), very different from the mean value of its sub-group. Two species, D. spinulosa and D. dichotoma, could not be included in any of these sub-groups. The former due to poor phytochemical information available when we started this study (but see Discussion); the latter since it yielded diterpenes of all three Groups I-III. This may be related to the fact t hat the plant material used for this chemical investigation had been collected from several regions of the world, or more probably because this alga, due to its great morphological variability and to badly defined limits, may in fact include a complex of species [9]. It should be noted t hat the species with the highest EAs values, produced, in general, the most functionalized diterpenes, i.e. had high OI values (species from sub-group B). Among these species, Dictyota cervicornis, from Brazil, showed the highest OI as well as EAs indexes. DISCUSSION AND CONCLUSIONS According to botanists, Dictyota acutiloba is a fully characterized species with well-defined limits [56]. The geographic distribution of this species is restricted to the Pacific tropical waters [56]. As mentioned above, D. acutiloba furnished diterpenes whose skeletons have not been found in any other species of the genus. All this may indicate an early independent evolutionary process. The four unidentified Dictyota species (numbered from 2 to 5) cannot be correlated with botanical data. However, they all seem to belong to this genus as far as the OI and EAs indexes are concerned (Fig. 4). Dictyota sp 1 is characterized by the presence of dolabellanes and not dolastanes as observed for all the other species in sub-group B. This fact led us to suspect t hat the taxonomical classification of this alga was wrong. Indeed, when this work was underway, the alga "Dictyota sp 1" was submitted to a novel biological classification and turned out to be actually a species of the genus Dilophus [33]. The poor phytochemical informatioin available for Dictyota dentata, D. indica and D. flabellata do not allow any correlation with botanical data; several of these species present taxonomic problems [8]. The OI and EAs indexes calculated for Dictyota prolificans were found to be very different from the mean values observed for sub-group C. This observation strongly suggested t ha t D. prolificans should not be included among the representatives of the genus Dictyota. Our assumption was in agreement with a recent botanical revision [56]. Indeed, Allender and Kraft, investigating the Australian Dictyotaceae, observed t ha t Dilophus prolificans (the alga from which prenylated bicyclogermacranes were isolated [41]) corresponded to the same plant as Dictyota prolificans. From morphological and reproductive studies, the authors adduced the synonymy, and included these specimens in a new combination, Dilophus intermedius (Zanardini) Allender and Kraft [56]. This is a typical example of a problem t hat would have been overlooked by a conventional study based on the presence or absence of metabolites, since the target compounds were in fact present, but their mean oxidation index was too small.

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Dictyota species. (1) Dictyota acutiloba ( 1.45, 0.13), (2) Dictyota binghamiae (-1.32, 0.09), (3) Dictyota cervicornis ( - 1.21, 0.17), (4) Dictyota crenulata ( 1.26, 0.08), (5) Dictyota dentata ( - 1.39, 0.10), (6) Dictyota dichotoma (-1.38, 0.10), (7) Dictyota divaricata (-1.24, 0.15), (8) Dictyota flabellata ( - 1.35, 0.08), (9) Dictyota indica ( - 1.40, 0.10), (10) Dictyota acutiloba ( - 1.45, 0.13), (11) Dictyota masonii ( - 1.50, 0.05), (12) Dictyota prolificans ( - 1.07, 0.07), (13) Dictyota spinulosa ( - 1.20, 0.05), (14) Dictyota sp 1 ( - 1.34, 0.10), (15) Dictyota sp 2 ( 1.33,0.09), (16) Dictyota sp 3 ( - 1.27, 0.15), (17) Dictyota sp 4 ( - 1.43, 0.13), (18) Dictyota sp 5 ( - 1.43, 0.11). D a w s o n [8] c o n s i d e r s D i c t y o t a b i n g h a m i a e to be s y n o n y m o u s w i t h Pachydictyon coriaceum. T h e f o r m e r a l g a p r o d u c e s d i t e r p e n e s of the x e n i a n e a n d of the p r e n y l a t e d g u a i a n e s k e l e t o n s , w h e r e a s P. coriaceum yields, in addition, d i t e r p e n e s of G r o u p II [7]. T h i s o b s e r v a t i o n c o n t r a d i c t s D a w s o n ' s proposal. D i c t y o t a cervicornis, D. d i v a r i c a t a a n d D. linearis, c h a r a c t e r i z e d c h e m i c a l l y by the p r e s e n c e of d o l a s t a n e s , are c o n s i d e r e d by b o t a n i s t s to be m o r p h o l o g i cally v e r y s i m i l a r [57]. O u r d a t a a g r e e w i t h this a s s u m p t i o n . D i c t y o t a sp 3 (from the C a n a r y Islands) m a y be one of t h e s e t h r e e species, w h i c h a r e w i d e s p r e a d in this a r e a [58]. N i z a m m u d d i n a n d Gerloff [59] c o n s i d e r Dictyota crenulata, f r o m the r e g i o n w h e r e this a l g a h a d b e e n collected for c h e m i c a l i n v e s t i g a t i o n , to be D i l o p h u s c r e n u l a t u s (J. Agardh). O u r d a t a r e v e a l t h a t the e x c l u s i o n of this species from t h e g e n u s D i c t y o t a a n d its i n c l u s i o n in t h e g e n u s D i l o p h u s should be pre-

279 cipitated, since the diterpene skeletons from Dictyota crenulata (crenulane and crenulidane) have been observed not only in Dilophus okamurai [60], but also in Pachydictyon coriaceum [61]. It is interesting to note that, with the exception of Dictyota spinulosa, for which limited phytochemical data was available when we started this study, all the species that produce diterpenes from Group III also produce diterpenes from Group I (i.e. sub-group C). this may indicate that the early biosynthetic steps leading to these two classes of diterpenes are common, and hence that the xeniane skeleton does not derive from a first anti-Markovnikov cyclization of geranyl-geraniol between C-2 and C-10 as is generally accepted [62] and as we depict in Fig. 1. Recently, Kakisawa et al. [63] proposed that xenianes are derived by ring contraction of a prenylated germacrane precursor. This proposal is in agreement with, and is corroborated by, our observations. From all this, it was tempting to speculate on the presence, in D. spinulosa, of diterpenes of Group I in addition to the already reported xeniane-type compound. A recent report [64] has confirmed this hypothesis and indicated that D. spinulosa belongs indeed to sub-group C. Finally, from the co-occurrence of dolabellane, dolastane and dictalane in an unidentified species of Dictyota from the Canary Islands, it has been proposed, in a preliminary communication [65], that the dictalane skeleton may derive from cyclization and rearrangement of a dolabellane precursor. If this is true, the dictalane skeleton should belong to Group II and not to Group I. Although coherent, a full paper has not yet appeared on this biosynthetic proposal. However, since there are no other records of the co-occurrence of dolabellanes and dolastanes, it is not impossible t h a t these results can be explained by a possible heterogeneity of the studied Dictyota sample. In this respect, one should note t h a t Dictyota dichotoma is the only species identified that yielded dolabellanes together with diterpenes of 10 other skeletons. But, even in this particulalry rich species, dolastanes do not co-occur with dolabellanes. All this indicates that diterpenes appear to be good taxonomic markers for the genus Dictyota, showing for various species strong correlations with botanic data. In addition, the lack of experimental biosynthetic work is also evident. Moreover, our results corroborate Gottlieb's Theory of Micromolecular Evolution [14], which states that higher oxidation levels are characteristic of evolutionarily more advanced components of a given taxon (first part of the Second Principle of Micromolecular Evolution). Hence, among the species that were studied chemically, the representatives of sub-group B (Fig. 4) appear to be the most evolved of the genus. EXPERIMENTAL OI and EAs indexes were calculated following Gottlieb [14]. Dictyota acutiloba (IO = - 1.45; EAs = 0.13), D. binghamiae ( - 1.35; 0.09), D. cervicor-

280

nis (-1.22; 0.16), D. crenulata (-1.26; 0.08), D. dentata (-1.39; 0.10), D. dichotoma ( - 1.38; 0.10), D. divaricata ( 1.23; 0.15), D. flabellata ( - 1.35; 0.08), D. indica (-1.40; 0.10), D. linearis ( 1.30; 0.15), D. masonii (-1.50; 0.05), D . prolificans (-1.07; 0.07), D. divaricata (-1.20; 0.05 corrected including d i t e r p e n e s r e p o r t e d i n r e f . 64: - 1.34; 0.06), Dictyota sp 1 ( - 1.34; 0.10), Dictyota sp 2 ( - 1.33; 0.09), Dictyota sp 3 ( - 1.27; 0.15), Dictyota sp 4 ( - 1.43; 0.13) a n d Dictyota sp 5 ( - 1.42; 0.11). ACKNOWLEDGEMENTS This work was financially V.L.T. thanks the Conselho

supported by CAPES, FINEP and CNPq grants. Nacional de Desenvolvimento Cientifico e Tec-

nologico (CNPq) for a fellowship.

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