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Terpenoids—XXXII
Tetrahedron. 1962. Vol. 18, pp, %9 to 977. Pcrgamon Press Ltd. PrInttd In Northern lreland
TERPENOIDS-XXX11 ABSOLUTE AND
CONFIGURATION OF JUNENOL SYNTHESIS OF JUNENOL FROM
AND LAEVOJUNENOL COSTUNOLIDE*
A. M. SHALIGRAM,A.S. RAO and S. ~.BHATTACHAR YYA National Chemical Laboratory,
Poona, India
(Received 23 March 1962)
Abstract-The North Indian vetivcr variety has yielded a new laevo-rotatory
crystalline sesquiterpene alcohol, which is named as laevojuncnol. It is the optical antipode of the previously isolated dextrorotatory alcohol, junenol. The absolute configuration of these two alcohols, which belong to eudesman group of compounds has been determined on the basis of the synthesis of dihydrojunenol from santanolide ‘c’. The dextrorotatory alcohol junenol has also been similarly synthesized from the new unsaturated lactone (XII), derived from the ten-membered carbccyclic lactone costunolide.
FROM vetiver oil (Vetiveria zizarkides, Linn)l of North Indian origin from Moosanagar area, we have isolated together with hydrocarbons and ketonic constituents, a new crystalline, monoethynoid, laevorotatory sesquiterpene alcohol,2 C15HX0, m.p. 65”, [& -57”. Its structure and stereochemistry are presented in this communication. The alcohol, obtained from the tail portion of the hydrocarbon fractions of the oil by column chromatography over alumina, was purified by crystallization and subIts IR spectrum (Fig. 1) shows the presence of an -OH group (3400 cm-l) limation. and a methylenic
C=CH, (1780, 1639,887 cm-l). Its NMR spectrum > shows the vinyl proton absorption at 5.16 and 5-45~. On catalytic hydrogenation in acetic acid using Adams catalyst, it absorbs one mole of hydrogen to give a dihydroproduct, C,,H2s0, m.p. 115”, [cc]D +O”. The IR spectrum (Fig. I) of the dihydrocompound shows a hydroxyl absorption at 3280 cm-l and disappearance of bands at 1780 and 1639 cm-l due to the saturation of the methylenic double bond. On ozonization, the parent alcohol gives formaldehyde and a keto-alcohol, C,,H,,O,, m.p. 45”, [aID -
double bond
1 f-5” (IR spectrum,
bands at 3540 cm-l
for -OH,
1700 cm-l
for )c-0).
On selenium dehydrogenation, it gives eudalene, characterized as pi&ate and s-trinitrobenzene derivatives. The properties of the parent alcohol, its dihydro derivative and the C,,-keto alcohol derived from it, agree in all respects with the properties reported for the sesquiterpene alcohol junenol and its corresponding derivatives, except for the respective rotation values, which are equal in magnitude, but opposite in sign. This led to the conclusion that the laevortatory alcohol is the optical antipode of the dextrorotatory alcohol junenol isolated by Sorm et al .3 from the essential oil of juniper berries. This contention is further confirmed by the identity of their IR spectra. Hence, we propose the name laevojunenol for the parent alcohol. * Contribution No. 490 from the National Chemical Laboratory, Poona-8, India. 1.Sadgopal and Bhatiya, I&. Soup J. 19, 198 (1954); Sadgopal, Soup, PerJ & Cosm. 33,298 (1960). 2 S. C. Bhattacharyya, A. S. Rao and A. M. Shaligram, Gent. & Irzd. 469 (1960). a V. Herout, 0. Motl, and F. Sorm, Coil. Czech. Chem. Comm. 19,990 (1954); 22,785 (1957).
969
A. M. SHALIGRAM,A. S. RAO and S. C.
970
BHAITACHARYYA
The Czech authors have assigned a selenenic structure (I) for junenol which was confirmed during the present investigations. As its laevoantipode, laevojunenol will also be represented by the same structure (I), a direct chemical proof for the location of the methylenic double bond at C, (15) in laevojunenol and consequently in junenol as well, was obtained as follows: The keto alcohol obtained by ozonization of laevojunenol was subjected to HuangMinlon reduction and subsequently to Se-dehydrogenation. The aromatic hydrocarbon thus obtained was identified as 24sopropylnapthalene (II) through its picrate and T.N.B. derivatives. An alternative possibility of $e structure containing the double bond in the isopropyl side chain, ruled out by Sorm et al., on the basis of ozonolysis data (negative iodoform test), would have given I-methyl-7-ethyl naphthalene on similar reactions, “sorm et al. established the gross structural formula (I) for junenol, but left its stereochemistry unsolved. The limited amount of laevojunenol at our disposal prevented our carrying out elaborate degradation experiments, to elucidate its absolute configuration It was considered more practicable to synthesize either junenol or laevojunenol or their corresponding dihydroderivatives from more easily accessible compounds of known configuration. Taking into consideration, the present knowledge of eudesmanic compounds,4 it was thought likely that either junenol or laevojunenol should possess the configuration (III) with the angular methyl group at C(10) and the isopropyl side chain at C, having /&configuration and the C, hydrogen x-oriented. * As the potential hydroxyl group in L-santonin and allied naturally occurring lactones is a-oriented, the -OH group was also assumed to be in the a-orientation . * Such a molecule on catalytic hydrogenation, due to the hydrogen attack from the x-face, should give a dihydro-product containing the C, methyl group /?-axially disposed6 (IV). From these considerations, santanolide ‘c’ of known configuration6 (V) was considered the suitable starting material for the synthesis of either dihydrolaevojunenol or dihydrojunenol. The scheme for this synthesis was to convert santanolide ‘c’ to the hydroxy aldehyde (VI) by controlled lithium aluminium hydride reduction,’ followed by Huang Minlon reduction of the aldehyde fragment to yield the desired alcohol (IV). F,ollowing the conditions as outlined by the original author for this reverse addition of lithium aluminium hydride, the more easily accessible santanolide ‘a’ (VII) used as a model compound, was converted by reduction in two stages to yield the highly crystalline alcohol (VIII), m.p. 53”. The IR spectrum of this compound shows a hydroxyl absorption at 3280 cm-r and as expected is different from that of dihydrolaevojunenol. By the same series of reactions santanolide ‘c’ was converted to the alcohol (1X) l
* There are some exceptions to this generalization though they are limited in number. Maaliol possess aconfiguration for the angular methyl group at C 10and /3configuration for the C& hydrogen [G. Btichi, M. Schach, V. Wittenau, and D. M. White, .I. Amer. Chem. Sot. 82, 1968, (1959)], while y-santonin possesses &configuration for the lactone attachment at Cs. [w. G. Dauben, J. S. P. Schwarz, W. K. Hayes, and P. D. Hance, J. Amer. Chem. Sm. 82,2239 (196O)J. ’ W. Cocker, and T. B. H. McMurry, Tetrahedron 8, 181 (1960), and references given therein. s D. H. R. Barton, Chem. & Ind. 664 (1953). 6 V. Herout and F. Sonn, Chem. & Ind. 1067 (1959). 7 G. E. Arth, J. Amer. Chem. Sm. 75,2413 (1953); see also E. Lederer, C. Asselineau and S. Bory, Bull. Sm. Chim. Fr. 1527 (1955).
Terpenoids-XXX11
971
which melted at 115”, [xl,-, *O”. Its IR spectrum (Fig. 1) is rich in detail and is completely superimposable with that of dihydrolaevojunenol. The NMR spectra of the synthetically prepared alcohol (IX) and dihydrolaevojunenol are also identical. From this, it is evident that the synthetic alcohol derived from santanolide ‘c’ and dihydrolaevojunenol are either identical or enantiomorphic. The identity of the IR and NMR spectra of these two akohols confirm the position of the -OH group at C,
Oihydroloevojunenol
D ihydrojunenol (IX) from scntMd1de “C”
frequency,
cm”
FIG. 1
and the angular methyl group at C,, in these two alcohols. Mixed m.p. of the alcohol (IX) and dihydrolaevojunenol, however, give a depression of about 20”, which conclusively proves that the synthetic alcohol (IX) derived from santanolide ‘c’ is not identical, and hence, must be enantiomorphic with dihydrolaevojunenol. This was further confirmed by the measurement of rotatory dispersion curves. Dihydrolaevojunenol gives a plain positive curve, while dihydrojunenol synthesized from santanolide ‘c’ gives a plain negative curve. The molecular rotation difference (AM = + 132) between junenol and dihydrojunenol is of the same sign as the molecular rotation difference (AM = + 108) between eudesmol and dihydroeudesmol,8 the two pairs of compounds compared being structurally and stereochemically similar. As expected, the molecular rotation difference (AM = - 129) between laevojunenol and dihydrolaevojunenol is negative but of the same magnitude as in the case of junenol and dihydrojunenol. Hence the absoIute configuration of junenol and consequently of laevojunenol and dihydrolaevojunenol can be depicted as X, XI and XIa BF. J. McQuilline and J. D. Parrack, J. Chem. Sot. 2973 (1956).
A. M. SHALERAM,
972
P
A. S. RAO and S. C. BHAITACHARYYA
m
Ix
Terpenoids-XXXII
973
respectively. Compared with eudesmol, laevojunenol has opposite configuration at ClO, CS and C, asymmetric centres. Biichi has shown that the sesquiterpene alcohol maaliol differs in absolute configuration from eudesmol at C,, and C, centres but not at C,. A survey of literature points out that the C, substituents in all eudesmanes and their derivatives are customarily considered as #?-oriented. In an excellent review4 Cocker and McMurry describe this centre of asymmetry as, “In all the eudesmans, where the configuration at C, is known, the isopropyl side chain is always p-oriented.” Laevojunenol is the first naturally occurring eudesmanic compound, having besides the C,,-angular methyl group, also the C,-side chain a-oriented. SYNTHESIS
OF JUNENOL
Based on the synthesis of dihydrojunenol, the lactone of the structure XII should also on similar sequence of reactions, give the dextrorotatory alcohol junenol itself. In this connection dihydrocostunolide (XIII) was a suitable starting material. On the basis of acid cyclization of pyrethrosin type of compounds,g it was likely that dihydrocostunolide would also on acid cyclization furnish, along with the previously isolated and reported 1actonelO (XIV), another unsaturated lactone (XII) containing an exocyclic double bond, if the cyclization proceeds via the carbonium ion (XV). The acid cyclization of dihydrocostunolidell gives a solid crystalline product which has several striking features, (i) its melting point (119”) is much lower than the m.p. 136-137” reported for the lactone (XIV), (ii) its IR spectrum shows bands at 1645 and 889 cm-l, suggesting the presence of an exocyclic double bond, and (iii) on ozonization it afford .s formaldehyde as a volatile fragment. It is evident from these observations that the cyclization product of dihydrocostunolide is a mixture of two unsaturated lactones, one of which is the exocyclic isomeride (XII). These two closely related lactones were separated by coIumn chromatography over alumina. The la&one (XIV) with an endocyclic double bond was eluted entirely with petroleum ether, while the Iatter (XII) could only be eIuted with acetic acid. This new unsaturated lactone, m.p. 140”, [a],, + 14U’ is assigned the structure XII on the following evidence. Chart II
H
+
Xii
* D. H. R. Barton and P. de Mayo, J. Chem. Sot. 151 ( 1957). lo W. Cocker and T. B. H. McMurry, J. Chem. Sac. 4549 (1956). *I A. Somasekhar Rao, G. R. Kelkar and S. C. Bhattacharyya, Tetrahedron
9, 275 (1960).
A. M.
SHALIGRAM,
A. S. RAO and S. C. BHAI-~ACHARYYA
Its IR spectrum (Fig. I) shows bands at 1633, 890 cm-l (
>
C=CH&,
1764 cm-l
(y-lactone) ; UV spectrum ~~~~ 377. On catalytic hydrogenation in acetic acid medium, it gives santanolide ‘a’. On ozonolysis, it gives formaldehyde and a keto-lactone (XVI) C,,H,,O,, m.p. 220”, [z],, +71”. (IR bands at 1757 and 1707 cm-l). The rotatory dispersion curve of this keto-lactone (XVI) (negative cume, amplitude a = -28) agrees well with the conclusion drawn from its octant diagram. The lactone (XII) was successfully converted to the dextrorotatory alcohol junenol following essentially the same scheme as used for the conversion of santanolide ‘c’ to dihydrojunenol. As it was considered that the homoallylic alcohof formed during the last reduction might dehydrate12 at higher temperature and in a high alkali concentration, the final reduction was carried out at a comparatively low temperature (150”) and in a low alkali concentration by taking a large excess of solvent. The synthetic alcohol thus obtained, melts at 61-62”, [&, +51”. Mixed m.p. with an authentic sample of naturally occurring junenol* was undepressed. The IR spectra of the synthetically prepared junenol, naturally occurring junenol, and of laevojunenol are identical. EXPERIMENTAL The essential oil obtained through Government Agencies was dried over sodium sulphate and distilled for investigation purposes. All the chroqatograms were carried out using acid washed alufnina of suitable grades, prepared and standardized in this laboratory. The pet ether refers to the fraction boiling between 60-80”. All the m.p. are uncorrected. The rotations, unless otherwise stated, were taken in ethanol (95%) solution. The UV spectra were measured in ethanol solution on a Beckman ratio recording spectrophotometer Model DK-2. The IR spectra were recorded & liquid film or in Nujol suspension on a Grubb Parson’s double beam spectrometer provided with sodium chloride optics. 1sola tion of iaevojunenol. The alcohol was obtained by column chromatography on alumina (grade IJI & II) of the hydrocarbon-rich fraction (b.p. 9&102”/0+5 mm). It was crystallized twice (pet ether), m.p. 65”, [aID -57” (c, l-18). (Found: C, 81.2; H, 1164. ClaHteO requires: C, 81.02; H, 11.7%). Dehydrogenation of iaevojunenol with Se. Laevojunenol (298 mg) was dehydrogenatecl with Se (446 mg) at 290” in an atmosphere of nitrogen for 16 hr. No blue colour was observed during dehydrogenat ion. The dehydrogenated product was &en up in a mixture of pet ether and benzene, concentrated to a small volume and filtered through alumina (grade I, 30 g) using pet ether as eluent. Evaporation of the solvent gave eudalene (228 mg), picrate m.p. and mixed m.p. with authentic sample 95-96”, T.N.B. derivative m-p. and mixed m.p. 112*5-l 13”. Hydrogenatiolz of faeoojunenof. Laevojunenol (I.024 g) was dissolved in glacial acetic acid (25 ml) and stirred in an atmosphere of hydrogen using Adams PtO, catalyst (40 mg) for 4 hr. Total uptake of hydrogen was equivalent to one double bond (130 ml/710 mm, 26”). Dihydrolaevojunenol thus obtained was sublimed (970 mg), m. p. 115’, [aJD 50” (c, 2.6). (Found : C, 80-3; H, 12.0. CIBHa80 requires: C, 80.29; H, 12.58%). Ozonofysis of laevojunenol. Laevojunenol(970 mg) was dissolved in dry ethyl acetate (60 ml) and ozonized in a dry stream of ozonized oxygen at -5” for 5 hr. The volatile fragment was collected in cold distilled water, which gave a positive test for formaldehyde (dimedone adduct, m.p. and mixed m.p. 188-l 89”). From the ozonide ethyl acetate was removed under red press at 40”, and the otonide was decomposed by adding water (30 ml), and heating on a steam bath for 4 hr. The aqueous layer was extracted with ether, washed with sodium bicarbonate and the neutral portion purified in the usual way. The liquid residue (820 mg) was distilled (135” bath temp/Oel mm) when it solidified. It was further sublimed to give the keto-alcohol (740 mg), m.p. 43”, [aID - 1 l-5” (c, 2.00) (Found: C, 74.46; H, 10.43. CI,H,,02 requires: C, 75-O; H, 10.74%). IR bands: 3540, 1700, 1464, 1426, * The authors express their sincere thanks to Prof. F. sorm for the sample of junenol. I2 G. Ohloff, Liebigs Am.
625,206
(1960); Chim. Ber. 90, 1554 (1957).
Telpenoids-XXXII
975
1386, 1366,1346,1310,1292,1267,1241,1216, 1183,1090,1062,1045, 1033,985,977,930,911, 897, 876,867 cm-l etc. (Nujol) Comrerson of laevojunenoi to 2-isopropyl naphthulene(Il). A mixture of the above keto-alcohol (420 mg), diethylene glycol (4 ml), potassium hydroxide pellets (400 mg), and hydrazine hydrate (O-7 ml, 85 %) was heated to 1 l&l 15” for 2 hr in an atmosphere of nitrogen, during which the contents were shaken from time to time. Water from the reaction mixture was removed by gradually heating it to 195” and the reaction mixture was refluxed at 190” for 4 hr more and cooled. The viscous reaction product was diluted with water (30 ml), neutralized with dilute hydrochloric acid at 0” and extracted with ether. The extract was made neutral, dried and evaporated. The crude brownish product (383 mg) was dehydrogenated with selenium (530 mg) at 280”, and the product was purified by chromatography over alumina (grade I, 30 g), The T.N.B. derivative was crystallized twice from ethanol, m.p. and mixed m.p. with an authentic sample of T.N.B. derivative of 2-isopropylnaphthalene 107”, while the mixed m.p. with the T.N.B. derivative of l-methyl-7-ethyl naphthalene (m.p. 107”) gave a depression of about 20”. Conuersjort ofsarrtanolide ‘a’ (VII) to the akohol (VIII). Santanolide ‘a’ (VII) was prepared from r-santonin according to the method given by Kovac ef al.‘* A solution of santanolide ‘a’ (VII) in dry ether (11.3 g in 100 ml) was stirred mechanically at -10”. To this, a solution of lithium aluminium hydride* (435 mg in 100 ml dry ether) was added during the period of 1 hr. After the addition, the solution was stirred for another 2 hr at initial temp and then allowed to come to room temp. The reaction mixture was carefully decomposed by adding a small quantity of water, extracted with ether, washed with water and dried. The removal of ether furnished a white amorphous solid (10.2 g) which gave a positive Fehling’s test. A portion of the above partially reduced product (3.17 8) was dissolved in freshly distilled diethylene glycol (14 ml) and hydrazine hydrate (6 ml, 85%) by heating over a steam-bath for 2 min. The solution was kept at room temp for 30 tin with occasional shaking. Potassium hydroxide pellets (3 g) were added and the solution refluxed at 1l&l 15” for 2 hr in an atmosphere of nitrogen. The water from the reaction mixture was removed by raising the temp to 195” and the reaction mixture was refluxed at 190” for 3 hr more with adequate arrangements to prevent any loss due to volatilization. The viscous reaction product was cooled, diluted with water (50 ml) and repeatedly extracted with ether. The ethereal layer was washed with water, dried and evaporated. The solid residue (700 mg) was chromatographed over alumina (grade III, 30 g) and eluted with a mixture of pet ether and benzene (9: 1, 200 ml). Evaporation of the solvent and sublimation gave the alcohol (VIII; 383 mg), m.p. 53-54”. (Found: C, 80.3; H, 12GO. CI,H,,O requires: C, 80.29; H, 12~58%). IR bands at: 3420, 1310, 1284, 1239, 1224, 1208, 1051, 1024, 1007, 990, 974, 943, 921, 903, 897, 857, 841, 822, 794, 752 cm-l etc. (Nujol) Preparation ofsantarwlide ‘c’. Costunolide, m.p. 106”, [&, + 128” (21.4 g) was hydrogenated in acetic acid (200 ml) containing perchloric acid (10 ml, 65 %) using platinum catalyst till the absorption of hydrogen ceased. The catalyst was filtered off, and acetic acid was distilled under red press (40” bath temp) till the total quantity was reduced to l/3 of the original volume. The residue was then neutralized with sodium carbonate, extracted with ether, washed twice with water and dried. The solvent was distilled off, and the thick viscous residue (20.4 g) crystallized twice from 95% ethanol to give santanolide ‘c’ (6.3 g), m.p. 153-154”, [& +54.9”. By the same procedure more santanolide ‘c’ was obtained by hydrogenating a crude mixture of costunolide and dehydrmstus lactone. The final product obtained was identical with the earlier sample in all respects. Synthesis of dihydrojuneml from sanfanolide ‘c’. Santanolide ‘c’ (9-9 g in 100 ml ether) was similarly treated as in the case of santanolide ‘a’ with lithium aluminium hydride (500 mg in 100 ml) and the resulting partially reduced product was further reduced by Huang Minlon reduction to give dihydrojunenol. It was purified by chromatography and sublimation (379 mg), m.p. 115”, [& f0” (c, 1-52). (Found: C, 80-52; H, 12-21. C,,H,,O requires: C, 80.29; H, 12.58%). Conversion ofdihydrocostunolide (XIII) to ju”enoi. Dihydrocostunloide, m.p. 77”, [& + 113’ was obtained from costunolide by hydrogenating costunolide in ethanol-Pd-C according to Rao et al.‘* * In all the controlled lithium aluminium hydride reductions described, a calculated quantity of the reagent after analysing (H. Felkin, Bull. Sot. Chim. Fr., 5,18,347, 1951), a commercial sample, was utilized. I3 S. 0. Kovac, V. Herout, M. Horak and F. Sorm, Co/l. Czech. Chem. Comm. 21,225 (1956).
A. M. SHAL~GRAM, A. S. RAO and S. C. BHA~ACHARYYA
976
It was cyclized in acetic acid and acetic anhydride medium by following the conditions given by the same authors. An additional quantity (62 g) of the cyclized mixture was obtained by utilizing the crude lactonic mixture of costunolide and dehydrocostus lactone. The chromatography on a pilot scale of the cyclized mixture (O-8 g, alumina grade III, 40 g) to separate the two isomers was not successful. The chromatogarphy of the entire lot (62 g) using alumina (grade III, 2-4 kg) and elution by different solvents gave: (i) (ii) (iii) (iv) (v)
Pet ether fraction Pet ether :benzene mixture (1: 1) fraction Benzene fraction Ethanol fraction Acetic acid fraction
10 1. 6 1. 6 1. 6 1. 6 1.
g
m.p. 128”
O-8 g 0.5 g o-5 g 24.5 g
m.p. 66” m.p. 66” m-p. 66” m.p. 132”
2’
The lactone (XIV) was isolated from pet ether fraction by repeated crystallization from ethanol and subsequently from hexane. The sublimed product melted at 140”, [x]~ +85” (c, 1.402 in CHCl,). (Found: C, 76.8; H, 9.71. C,,H,J& requires: C, 76.88; H, 9.46%). UV spectrum (ethanol), &Z1o,2871 ; &z16 1435, eaeo 385. Hydrqgenution of the luclone (XIV) to sanlunolide ‘c’. The lactone (XIV; 49 mg) was dissolved in acetic acid and hydrogenated using Adams catalyst till saturation. The hydrogenated product was taken up in ether and purified in the usual way. The sublimed sample melted at 153”, mixed m.p. with santanolide ‘c’ gave no depression. Its IR spectrum was identical with that of santanolide ‘ I C.
Isolution of /aclone (X11). The acetic acid eluted fraction of the chromatography of the cyclized product, m.p. 132”, was crystallized from pentane several times and sublimed. m-p. l#“, [aID + 140” (c, 3.5 CHCl,). (Found: C, 77.0; H, 9-4. C,,H,,O, requires: C, 76.88; H, 9.71 yd), UV spectrum &ZlO377; &ala120, Eg.20 75. The lactone was hydrogenated in acetic acid using platinum catalyst till saturation. The resulting product on purification melted at 154’, mixed m-p. with santanolide ‘a’ was not depressed and its IR spectrum was identical with santanolide ‘a’. Ozomlysis offhe &tone (X11) to kefo lucione (XVI). The lactone (XII; 1-l g) was dissolved in dry ethyl acetate (30 ml) and ozonized for 5 hr at - 5”. The volatile products trapped in cold distilled water gave a positive test for formaldehyde. The ozonide was worked up in the usual way and the resulting keto-lactonc (XVI) was crystallized from ethanol and sublimed (800 mg), (150” bath ternpI 0.05 mm), m.p. 220”, [a],-, -t 71”,48” (c, 1.525 CHCl,). (Found: C, 71.7; H, 8.8. C,,H,,O, requires: C, 71.2; H, 8.58%). IR bands at: 1757, 1706, 1461,1424, 1380,1359, 1304, 1263, 1242,1215, 1194, 1173, 1153, 1129, 1084, 1059, 1038, 1025, 1004, 990, 956, 924, 893, 871, 854, 835, 756 cm-l etc. (Nujol) Conversion of lactone (XII) to junenol. The dry unsaturated lactone (XII; 7.15 g) was dissolved in dry ether (150 ml) and cooled to -. 10”. A solution of lithium aluminium hydride in dry ether (420 mg in 100 ml) was slowly added to it during the period of 1 hr with mechanical stirring. Stirring was continued for 2 hr more at - 10” and for another hr at room temp. The ether layer was washed with water, dried and evaporated under red press. The resulting white amorphous solid (6.9 8, was utilized for the final Hunag Minlon reduction. The partially reduced lactone (6.8 g) described above was dissolved in a mixture of freshly distilled diethylene glycol (40 ml) and hydrazine hydrate (11 ml, 85 “//,) by heating on a steam bath for 5 min when a clear homogenous solution resulted. This was kept at room temp for 30 min. Potassium hydroxide pellets (6 g) were added and the solution was refluxed at 110-l 15” for 2 hr and allowed to cool to 60”. Dry benzene (20 ml) was then added to the solution. The contents of the flask were shaken thoroughly and benzene was carefully removed by heating the reaction mixture to 130”. This prt>cedure was repeated 3 times in order to remove water from the reaction mixture. Finally the solution was refluxed at 150” for 2 hr and cooled. The viscous transparent mass was diluted with water (50 ml) repeatedly extracted with ether, the ether layer washed twice with water, dried and evaporated. The residue (800 mg) was chromatographed (alumina, grade III, 30 g) and the column eluted with pet ether-benzene mixture (9: 1, 200 ml). Evaporation of solvent gave junenol, crystallized from pet ether, sublimed m.p. 61-62’, [=I,, i 51” (c, 2.45). (Found: C, 81-2; ,H, 11.9. C1&HfsO requires; C, 81.8; H, 11.7%).
Terpenoids-XXXII
977
Ackrrowf&gemenr.s--The authors express their sincere thanks to Drs. A. K. Bose and E. R. Malinowski, Stevens Institute of Technology, Hoboken, N.J. for the NMR and RD curves described in the paper. They also thank Prof. W. Klyne, Westfield College, University of London, for the measurement and interpretation of the RD curve of the compound (XVI). All the IR spectra were taken by Mr. Jose and his colleagues and the microanalyses were done by Mr. Pansare and his associates of this laboratory. One of the authors (A. M. Shaligram) is grateful to the Council of Scientific and Industrial Research, Government of India, for the award of Junior Research Fellowship to him during the period of this work.
TERPENOIDS-XXX11 ABSOLUTE AND
CONFIGURATION OF JUNENOL SYNTHESIS OF JUNENOL FROM
AND LAEVOJUNENOL COSTUNOLIDE*
A. M. SHALIGRAM,A.S. RAO and S. ~.BHATTACHAR YYA National Chemical Laboratory,
Poona, India
(Received 23 March 1962)
Abstract-The North Indian vetivcr variety has yielded a new laevo-rotatory
crystalline sesquiterpene alcohol, which is named as laevojuncnol. It is the optical antipode of the previously isolated dextrorotatory alcohol, junenol. The absolute configuration of these two alcohols, which belong to eudesman group of compounds has been determined on the basis of the synthesis of dihydrojunenol from santanolide ‘c’. The dextrorotatory alcohol junenol has also been similarly synthesized from the new unsaturated lactone (XII), derived from the ten-membered carbccyclic lactone costunolide.
FROM vetiver oil (Vetiveria zizarkides, Linn)l of North Indian origin from Moosanagar area, we have isolated together with hydrocarbons and ketonic constituents, a new crystalline, monoethynoid, laevorotatory sesquiterpene alcohol,2 C15HX0, m.p. 65”, [& -57”. Its structure and stereochemistry are presented in this communication. The alcohol, obtained from the tail portion of the hydrocarbon fractions of the oil by column chromatography over alumina, was purified by crystallization and subIts IR spectrum (Fig. 1) shows the presence of an -OH group (3400 cm-l) limation. and a methylenic
C=CH, (1780, 1639,887 cm-l). Its NMR spectrum > shows the vinyl proton absorption at 5.16 and 5-45~. On catalytic hydrogenation in acetic acid using Adams catalyst, it absorbs one mole of hydrogen to give a dihydroproduct, C,,H2s0, m.p. 115”, [cc]D +O”. The IR spectrum (Fig. I) of the dihydrocompound shows a hydroxyl absorption at 3280 cm-l and disappearance of bands at 1780 and 1639 cm-l due to the saturation of the methylenic double bond. On ozonization, the parent alcohol gives formaldehyde and a keto-alcohol, C,,H,,O,, m.p. 45”, [aID -
double bond
1 f-5” (IR spectrum,
bands at 3540 cm-l
for -OH,
1700 cm-l
for )c-0).
On selenium dehydrogenation, it gives eudalene, characterized as pi&ate and s-trinitrobenzene derivatives. The properties of the parent alcohol, its dihydro derivative and the C,,-keto alcohol derived from it, agree in all respects with the properties reported for the sesquiterpene alcohol junenol and its corresponding derivatives, except for the respective rotation values, which are equal in magnitude, but opposite in sign. This led to the conclusion that the laevortatory alcohol is the optical antipode of the dextrorotatory alcohol junenol isolated by Sorm et al .3 from the essential oil of juniper berries. This contention is further confirmed by the identity of their IR spectra. Hence, we propose the name laevojunenol for the parent alcohol. * Contribution No. 490 from the National Chemical Laboratory, Poona-8, India. 1.Sadgopal and Bhatiya, I&. Soup J. 19, 198 (1954); Sadgopal, Soup, PerJ & Cosm. 33,298 (1960). 2 S. C. Bhattacharyya, A. S. Rao and A. M. Shaligram, Gent. & Irzd. 469 (1960). a V. Herout, 0. Motl, and F. Sorm, Coil. Czech. Chem. Comm. 19,990 (1954); 22,785 (1957).
969
A. M. SHALIGRAM,A. S. RAO and S. C.
970
BHAITACHARYYA
The Czech authors have assigned a selenenic structure (I) for junenol which was confirmed during the present investigations. As its laevoantipode, laevojunenol will also be represented by the same structure (I), a direct chemical proof for the location of the methylenic double bond at C, (15) in laevojunenol and consequently in junenol as well, was obtained as follows: The keto alcohol obtained by ozonization of laevojunenol was subjected to HuangMinlon reduction and subsequently to Se-dehydrogenation. The aromatic hydrocarbon thus obtained was identified as 24sopropylnapthalene (II) through its picrate and T.N.B. derivatives. An alternative possibility of $e structure containing the double bond in the isopropyl side chain, ruled out by Sorm et al., on the basis of ozonolysis data (negative iodoform test), would have given I-methyl-7-ethyl naphthalene on similar reactions, “sorm et al. established the gross structural formula (I) for junenol, but left its stereochemistry unsolved. The limited amount of laevojunenol at our disposal prevented our carrying out elaborate degradation experiments, to elucidate its absolute configuration It was considered more practicable to synthesize either junenol or laevojunenol or their corresponding dihydroderivatives from more easily accessible compounds of known configuration. Taking into consideration, the present knowledge of eudesmanic compounds,4 it was thought likely that either junenol or laevojunenol should possess the configuration (III) with the angular methyl group at C(10) and the isopropyl side chain at C, having /&configuration and the C, hydrogen x-oriented. * As the potential hydroxyl group in L-santonin and allied naturally occurring lactones is a-oriented, the -OH group was also assumed to be in the a-orientation . * Such a molecule on catalytic hydrogenation, due to the hydrogen attack from the x-face, should give a dihydro-product containing the C, methyl group /?-axially disposed6 (IV). From these considerations, santanolide ‘c’ of known configuration6 (V) was considered the suitable starting material for the synthesis of either dihydrolaevojunenol or dihydrojunenol. The scheme for this synthesis was to convert santanolide ‘c’ to the hydroxy aldehyde (VI) by controlled lithium aluminium hydride reduction,’ followed by Huang Minlon reduction of the aldehyde fragment to yield the desired alcohol (IV). F,ollowing the conditions as outlined by the original author for this reverse addition of lithium aluminium hydride, the more easily accessible santanolide ‘a’ (VII) used as a model compound, was converted by reduction in two stages to yield the highly crystalline alcohol (VIII), m.p. 53”. The IR spectrum of this compound shows a hydroxyl absorption at 3280 cm-r and as expected is different from that of dihydrolaevojunenol. By the same series of reactions santanolide ‘c’ was converted to the alcohol (1X) l
* There are some exceptions to this generalization though they are limited in number. Maaliol possess aconfiguration for the angular methyl group at C 10and /3configuration for the C& hydrogen [G. Btichi, M. Schach, V. Wittenau, and D. M. White, .I. Amer. Chem. Sot. 82, 1968, (1959)], while y-santonin possesses &configuration for the lactone attachment at Cs. [w. G. Dauben, J. S. P. Schwarz, W. K. Hayes, and P. D. Hance, J. Amer. Chem. Sm. 82,2239 (196O)J. ’ W. Cocker, and T. B. H. McMurry, Tetrahedron 8, 181 (1960), and references given therein. s D. H. R. Barton, Chem. & Ind. 664 (1953). 6 V. Herout and F. Sonn, Chem. & Ind. 1067 (1959). 7 G. E. Arth, J. Amer. Chem. Sm. 75,2413 (1953); see also E. Lederer, C. Asselineau and S. Bory, Bull. Sm. Chim. Fr. 1527 (1955).
Terpenoids-XXX11
971
which melted at 115”, [xl,-, *O”. Its IR spectrum (Fig. 1) is rich in detail and is completely superimposable with that of dihydrolaevojunenol. The NMR spectra of the synthetically prepared alcohol (IX) and dihydrolaevojunenol are also identical. From this, it is evident that the synthetic alcohol derived from santanolide ‘c’ and dihydrolaevojunenol are either identical or enantiomorphic. The identity of the IR and NMR spectra of these two akohols confirm the position of the -OH group at C,
Oihydroloevojunenol
D ihydrojunenol (IX) from scntMd1de “C”
frequency,
cm”
FIG. 1
and the angular methyl group at C,, in these two alcohols. Mixed m.p. of the alcohol (IX) and dihydrolaevojunenol, however, give a depression of about 20”, which conclusively proves that the synthetic alcohol (IX) derived from santanolide ‘c’ is not identical, and hence, must be enantiomorphic with dihydrolaevojunenol. This was further confirmed by the measurement of rotatory dispersion curves. Dihydrolaevojunenol gives a plain positive curve, while dihydrojunenol synthesized from santanolide ‘c’ gives a plain negative curve. The molecular rotation difference (AM = + 132) between junenol and dihydrojunenol is of the same sign as the molecular rotation difference (AM = + 108) between eudesmol and dihydroeudesmol,8 the two pairs of compounds compared being structurally and stereochemically similar. As expected, the molecular rotation difference (AM = - 129) between laevojunenol and dihydrolaevojunenol is negative but of the same magnitude as in the case of junenol and dihydrojunenol. Hence the absoIute configuration of junenol and consequently of laevojunenol and dihydrolaevojunenol can be depicted as X, XI and XIa BF. J. McQuilline and J. D. Parrack, J. Chem. Sot. 2973 (1956).
A. M. SHALERAM,
972
P
A. S. RAO and S. C. BHAITACHARYYA
m
Ix
Terpenoids-XXXII
973
respectively. Compared with eudesmol, laevojunenol has opposite configuration at ClO, CS and C, asymmetric centres. Biichi has shown that the sesquiterpene alcohol maaliol differs in absolute configuration from eudesmol at C,, and C, centres but not at C,. A survey of literature points out that the C, substituents in all eudesmanes and their derivatives are customarily considered as #?-oriented. In an excellent review4 Cocker and McMurry describe this centre of asymmetry as, “In all the eudesmans, where the configuration at C, is known, the isopropyl side chain is always p-oriented.” Laevojunenol is the first naturally occurring eudesmanic compound, having besides the C,,-angular methyl group, also the C,-side chain a-oriented. SYNTHESIS
OF JUNENOL
Based on the synthesis of dihydrojunenol, the lactone of the structure XII should also on similar sequence of reactions, give the dextrorotatory alcohol junenol itself. In this connection dihydrocostunolide (XIII) was a suitable starting material. On the basis of acid cyclization of pyrethrosin type of compounds,g it was likely that dihydrocostunolide would also on acid cyclization furnish, along with the previously isolated and reported 1actonelO (XIV), another unsaturated lactone (XII) containing an exocyclic double bond, if the cyclization proceeds via the carbonium ion (XV). The acid cyclization of dihydrocostunolidell gives a solid crystalline product which has several striking features, (i) its melting point (119”) is much lower than the m.p. 136-137” reported for the lactone (XIV), (ii) its IR spectrum shows bands at 1645 and 889 cm-l, suggesting the presence of an exocyclic double bond, and (iii) on ozonization it afford .s formaldehyde as a volatile fragment. It is evident from these observations that the cyclization product of dihydrocostunolide is a mixture of two unsaturated lactones, one of which is the exocyclic isomeride (XII). These two closely related lactones were separated by coIumn chromatography over alumina. The la&one (XIV) with an endocyclic double bond was eluted entirely with petroleum ether, while the Iatter (XII) could only be eIuted with acetic acid. This new unsaturated lactone, m.p. 140”, [a],, + 14U’ is assigned the structure XII on the following evidence. Chart II
H
+
Xii
* D. H. R. Barton and P. de Mayo, J. Chem. Sot. 151 ( 1957). lo W. Cocker and T. B. H. McMurry, J. Chem. Sac. 4549 (1956). *I A. Somasekhar Rao, G. R. Kelkar and S. C. Bhattacharyya, Tetrahedron
9, 275 (1960).
A. M.
SHALIGRAM,
A. S. RAO and S. C. BHAI-~ACHARYYA
Its IR spectrum (Fig. I) shows bands at 1633, 890 cm-l (
>
C=CH&,
1764 cm-l
(y-lactone) ; UV spectrum ~~~~ 377. On catalytic hydrogenation in acetic acid medium, it gives santanolide ‘a’. On ozonolysis, it gives formaldehyde and a keto-lactone (XVI) C,,H,,O,, m.p. 220”, [z],, +71”. (IR bands at 1757 and 1707 cm-l). The rotatory dispersion curve of this keto-lactone (XVI) (negative cume, amplitude a = -28) agrees well with the conclusion drawn from its octant diagram. The lactone (XII) was successfully converted to the dextrorotatory alcohol junenol following essentially the same scheme as used for the conversion of santanolide ‘c’ to dihydrojunenol. As it was considered that the homoallylic alcohof formed during the last reduction might dehydrate12 at higher temperature and in a high alkali concentration, the final reduction was carried out at a comparatively low temperature (150”) and in a low alkali concentration by taking a large excess of solvent. The synthetic alcohol thus obtained, melts at 61-62”, [&, +51”. Mixed m.p. with an authentic sample of naturally occurring junenol* was undepressed. The IR spectra of the synthetically prepared junenol, naturally occurring junenol, and of laevojunenol are identical. EXPERIMENTAL The essential oil obtained through Government Agencies was dried over sodium sulphate and distilled for investigation purposes. All the chroqatograms were carried out using acid washed alufnina of suitable grades, prepared and standardized in this laboratory. The pet ether refers to the fraction boiling between 60-80”. All the m.p. are uncorrected. The rotations, unless otherwise stated, were taken in ethanol (95%) solution. The UV spectra were measured in ethanol solution on a Beckman ratio recording spectrophotometer Model DK-2. The IR spectra were recorded & liquid film or in Nujol suspension on a Grubb Parson’s double beam spectrometer provided with sodium chloride optics. 1sola tion of iaevojunenol. The alcohol was obtained by column chromatography on alumina (grade IJI & II) of the hydrocarbon-rich fraction (b.p. 9&102”/0+5 mm). It was crystallized twice (pet ether), m.p. 65”, [aID -57” (c, l-18). (Found: C, 81.2; H, 1164. ClaHteO requires: C, 81.02; H, 11.7%). Dehydrogenation of iaevojunenol with Se. Laevojunenol (298 mg) was dehydrogenatecl with Se (446 mg) at 290” in an atmosphere of nitrogen for 16 hr. No blue colour was observed during dehydrogenat ion. The dehydrogenated product was &en up in a mixture of pet ether and benzene, concentrated to a small volume and filtered through alumina (grade I, 30 g) using pet ether as eluent. Evaporation of the solvent gave eudalene (228 mg), picrate m.p. and mixed m.p. with authentic sample 95-96”, T.N.B. derivative m-p. and mixed m.p. 112*5-l 13”. Hydrogenatiolz of faeoojunenof. Laevojunenol (I.024 g) was dissolved in glacial acetic acid (25 ml) and stirred in an atmosphere of hydrogen using Adams PtO, catalyst (40 mg) for 4 hr. Total uptake of hydrogen was equivalent to one double bond (130 ml/710 mm, 26”). Dihydrolaevojunenol thus obtained was sublimed (970 mg), m. p. 115’, [aJD 50” (c, 2.6). (Found : C, 80-3; H, 12.0. CIBHa80 requires: C, 80.29; H, 12.58%). Ozonofysis of laevojunenol. Laevojunenol(970 mg) was dissolved in dry ethyl acetate (60 ml) and ozonized in a dry stream of ozonized oxygen at -5” for 5 hr. The volatile fragment was collected in cold distilled water, which gave a positive test for formaldehyde (dimedone adduct, m.p. and mixed m.p. 188-l 89”). From the ozonide ethyl acetate was removed under red press at 40”, and the otonide was decomposed by adding water (30 ml), and heating on a steam bath for 4 hr. The aqueous layer was extracted with ether, washed with sodium bicarbonate and the neutral portion purified in the usual way. The liquid residue (820 mg) was distilled (135” bath temp/Oel mm) when it solidified. It was further sublimed to give the keto-alcohol (740 mg), m.p. 43”, [aID - 1 l-5” (c, 2.00) (Found: C, 74.46; H, 10.43. CI,H,,02 requires: C, 75-O; H, 10.74%). IR bands: 3540, 1700, 1464, 1426, * The authors express their sincere thanks to Prof. F. sorm for the sample of junenol. I2 G. Ohloff, Liebigs Am.
625,206
(1960); Chim. Ber. 90, 1554 (1957).
Telpenoids-XXXII
975
1386, 1366,1346,1310,1292,1267,1241,1216, 1183,1090,1062,1045, 1033,985,977,930,911, 897, 876,867 cm-l etc. (Nujol) Comrerson of laevojunenoi to 2-isopropyl naphthulene(Il). A mixture of the above keto-alcohol (420 mg), diethylene glycol (4 ml), potassium hydroxide pellets (400 mg), and hydrazine hydrate (O-7 ml, 85 %) was heated to 1 l&l 15” for 2 hr in an atmosphere of nitrogen, during which the contents were shaken from time to time. Water from the reaction mixture was removed by gradually heating it to 195” and the reaction mixture was refluxed at 190” for 4 hr more and cooled. The viscous reaction product was diluted with water (30 ml), neutralized with dilute hydrochloric acid at 0” and extracted with ether. The extract was made neutral, dried and evaporated. The crude brownish product (383 mg) was dehydrogenated with selenium (530 mg) at 280”, and the product was purified by chromatography over alumina (grade I, 30 g), The T.N.B. derivative was crystallized twice from ethanol, m.p. and mixed m.p. with an authentic sample of T.N.B. derivative of 2-isopropylnaphthalene 107”, while the mixed m.p. with the T.N.B. derivative of l-methyl-7-ethyl naphthalene (m.p. 107”) gave a depression of about 20”. Conuersjort ofsarrtanolide ‘a’ (VII) to the akohol (VIII). Santanolide ‘a’ (VII) was prepared from r-santonin according to the method given by Kovac ef al.‘* A solution of santanolide ‘a’ (VII) in dry ether (11.3 g in 100 ml) was stirred mechanically at -10”. To this, a solution of lithium aluminium hydride* (435 mg in 100 ml dry ether) was added during the period of 1 hr. After the addition, the solution was stirred for another 2 hr at initial temp and then allowed to come to room temp. The reaction mixture was carefully decomposed by adding a small quantity of water, extracted with ether, washed with water and dried. The removal of ether furnished a white amorphous solid (10.2 g) which gave a positive Fehling’s test. A portion of the above partially reduced product (3.17 8) was dissolved in freshly distilled diethylene glycol (14 ml) and hydrazine hydrate (6 ml, 85%) by heating over a steam-bath for 2 min. The solution was kept at room temp for 30 tin with occasional shaking. Potassium hydroxide pellets (3 g) were added and the solution refluxed at 1l&l 15” for 2 hr in an atmosphere of nitrogen. The water from the reaction mixture was removed by raising the temp to 195” and the reaction mixture was refluxed at 190” for 3 hr more with adequate arrangements to prevent any loss due to volatilization. The viscous reaction product was cooled, diluted with water (50 ml) and repeatedly extracted with ether. The ethereal layer was washed with water, dried and evaporated. The solid residue (700 mg) was chromatographed over alumina (grade III, 30 g) and eluted with a mixture of pet ether and benzene (9: 1, 200 ml). Evaporation of the solvent and sublimation gave the alcohol (VIII; 383 mg), m.p. 53-54”. (Found: C, 80.3; H, 12GO. CI,H,,O requires: C, 80.29; H, 12~58%). IR bands at: 3420, 1310, 1284, 1239, 1224, 1208, 1051, 1024, 1007, 990, 974, 943, 921, 903, 897, 857, 841, 822, 794, 752 cm-l etc. (Nujol) Preparation ofsantarwlide ‘c’. Costunolide, m.p. 106”, [&, + 128” (21.4 g) was hydrogenated in acetic acid (200 ml) containing perchloric acid (10 ml, 65 %) using platinum catalyst till the absorption of hydrogen ceased. The catalyst was filtered off, and acetic acid was distilled under red press (40” bath temp) till the total quantity was reduced to l/3 of the original volume. The residue was then neutralized with sodium carbonate, extracted with ether, washed twice with water and dried. The solvent was distilled off, and the thick viscous residue (20.4 g) crystallized twice from 95% ethanol to give santanolide ‘c’ (6.3 g), m.p. 153-154”, [& +54.9”. By the same procedure more santanolide ‘c’ was obtained by hydrogenating a crude mixture of costunolide and dehydrmstus lactone. The final product obtained was identical with the earlier sample in all respects. Synthesis of dihydrojuneml from sanfanolide ‘c’. Santanolide ‘c’ (9-9 g in 100 ml ether) was similarly treated as in the case of santanolide ‘a’ with lithium aluminium hydride (500 mg in 100 ml) and the resulting partially reduced product was further reduced by Huang Minlon reduction to give dihydrojunenol. It was purified by chromatography and sublimation (379 mg), m.p. 115”, [& f0” (c, 1-52). (Found: C, 80-52; H, 12-21. C,,H,,O requires: C, 80.29; H, 12.58%). Conversion ofdihydrocostunolide (XIII) to ju”enoi. Dihydrocostunloide, m.p. 77”, [& + 113’ was obtained from costunolide by hydrogenating costunolide in ethanol-Pd-C according to Rao et al.‘* * In all the controlled lithium aluminium hydride reductions described, a calculated quantity of the reagent after analysing (H. Felkin, Bull. Sot. Chim. Fr., 5,18,347, 1951), a commercial sample, was utilized. I3 S. 0. Kovac, V. Herout, M. Horak and F. Sorm, Co/l. Czech. Chem. Comm. 21,225 (1956).
A. M. SHAL~GRAM, A. S. RAO and S. C. BHA~ACHARYYA
976
It was cyclized in acetic acid and acetic anhydride medium by following the conditions given by the same authors. An additional quantity (62 g) of the cyclized mixture was obtained by utilizing the crude lactonic mixture of costunolide and dehydrocostus lactone. The chromatography on a pilot scale of the cyclized mixture (O-8 g, alumina grade III, 40 g) to separate the two isomers was not successful. The chromatogarphy of the entire lot (62 g) using alumina (grade III, 2-4 kg) and elution by different solvents gave: (i) (ii) (iii) (iv) (v)
Pet ether fraction Pet ether :benzene mixture (1: 1) fraction Benzene fraction Ethanol fraction Acetic acid fraction
10 1. 6 1. 6 1. 6 1. 6 1.
g
m.p. 128”
O-8 g 0.5 g o-5 g 24.5 g
m.p. 66” m.p. 66” m-p. 66” m.p. 132”
2’
The lactone (XIV) was isolated from pet ether fraction by repeated crystallization from ethanol and subsequently from hexane. The sublimed product melted at 140”, [x]~ +85” (c, 1.402 in CHCl,). (Found: C, 76.8; H, 9.71. C,,H,J& requires: C, 76.88; H, 9.46%). UV spectrum (ethanol), &Z1o,2871 ; &z16 1435, eaeo 385. Hydrqgenution of the luclone (XIV) to sanlunolide ‘c’. The lactone (XIV; 49 mg) was dissolved in acetic acid and hydrogenated using Adams catalyst till saturation. The hydrogenated product was taken up in ether and purified in the usual way. The sublimed sample melted at 153”, mixed m.p. with santanolide ‘c’ gave no depression. Its IR spectrum was identical with that of santanolide ‘ I C.
Isolution of /aclone (X11). The acetic acid eluted fraction of the chromatography of the cyclized product, m.p. 132”, was crystallized from pentane several times and sublimed. m-p. l#“, [aID + 140” (c, 3.5 CHCl,). (Found: C, 77.0; H, 9-4. C,,H,,O, requires: C, 76.88; H, 9.71 yd), UV spectrum &ZlO377; &ala120, Eg.20 75. The lactone was hydrogenated in acetic acid using platinum catalyst till saturation. The resulting product on purification melted at 154’, mixed m-p. with santanolide ‘a’ was not depressed and its IR spectrum was identical with santanolide ‘a’. Ozomlysis offhe &tone (X11) to kefo lucione (XVI). The lactone (XII; 1-l g) was dissolved in dry ethyl acetate (30 ml) and ozonized for 5 hr at - 5”. The volatile products trapped in cold distilled water gave a positive test for formaldehyde. The ozonide was worked up in the usual way and the resulting keto-lactonc (XVI) was crystallized from ethanol and sublimed (800 mg), (150” bath ternpI 0.05 mm), m.p. 220”, [a],-, -t 71”,48” (c, 1.525 CHCl,). (Found: C, 71.7; H, 8.8. C,,H,,O, requires: C, 71.2; H, 8.58%). IR bands at: 1757, 1706, 1461,1424, 1380,1359, 1304, 1263, 1242,1215, 1194, 1173, 1153, 1129, 1084, 1059, 1038, 1025, 1004, 990, 956, 924, 893, 871, 854, 835, 756 cm-l etc. (Nujol) Conversion of lactone (XII) to junenol. The dry unsaturated lactone (XII; 7.15 g) was dissolved in dry ether (150 ml) and cooled to -. 10”. A solution of lithium aluminium hydride in dry ether (420 mg in 100 ml) was slowly added to it during the period of 1 hr with mechanical stirring. Stirring was continued for 2 hr more at - 10” and for another hr at room temp. The ether layer was washed with water, dried and evaporated under red press. The resulting white amorphous solid (6.9 8, was utilized for the final Hunag Minlon reduction. The partially reduced lactone (6.8 g) described above was dissolved in a mixture of freshly distilled diethylene glycol (40 ml) and hydrazine hydrate (11 ml, 85 “//,) by heating on a steam bath for 5 min when a clear homogenous solution resulted. This was kept at room temp for 30 min. Potassium hydroxide pellets (6 g) were added and the solution was refluxed at 110-l 15” for 2 hr and allowed to cool to 60”. Dry benzene (20 ml) was then added to the solution. The contents of the flask were shaken thoroughly and benzene was carefully removed by heating the reaction mixture to 130”. This prt>cedure was repeated 3 times in order to remove water from the reaction mixture. Finally the solution was refluxed at 150” for 2 hr and cooled. The viscous transparent mass was diluted with water (50 ml) repeatedly extracted with ether, the ether layer washed twice with water, dried and evaporated. The residue (800 mg) was chromatographed (alumina, grade III, 30 g) and the column eluted with pet ether-benzene mixture (9: 1, 200 ml). Evaporation of solvent gave junenol, crystallized from pet ether, sublimed m.p. 61-62’, [=I,, i 51” (c, 2.45). (Found: C, 81-2; ,H, 11.9. C1&HfsO requires; C, 81.8; H, 11.7%).
Terpenoids-XXXII
977
Ackrrowf&gemenr.s--The authors express their sincere thanks to Drs. A. K. Bose and E. R. Malinowski, Stevens Institute of Technology, Hoboken, N.J. for the NMR and RD curves described in the paper. They also thank Prof. W. Klyne, Westfield College, University of London, for the measurement and interpretation of the RD curve of the compound (XVI). All the IR spectra were taken by Mr. Jose and his colleagues and the microanalyses were done by Mr. Pansare and his associates of this laboratory. One of the authors (A. M. Shaligram) is grateful to the Council of Scientific and Industrial Research, Government of India, for the award of Junior Research Fellowship to him during the period of this work.