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Chemistry of terminalia species—VI
Tcuakdron.
1962. Vol.
18. pp. 827 to 838.
CHEMISTRY
l’er@mon
Prca
Ud.
Phted
In North
OF TERMINALIA
Imhnd
SPECIES-VI
THE CONSTITUTION OF TOMENTOSIC ACID, A NEW TRITERPENE CARBOXYLIC ACID FROM TERMINALIA TOMENTOSA WIGHT ET ARN” L. RAMACHANDRA Row and G. S. R. SUBBA RAO Department of Chemistry, Andhra University, Waltair, India (Receiued 1 February 1962) Abstract-From the heartwood of T. tomentusu Wight et Am, /?-sitosterol, oleanolic acid (VI, R = R, = H), arjunolic acid (I) and barringtogenol (IV) were isolated and in addition a new tetrahydroxy triterpene mono-carboxylic acid, now named Tomentosic acid. The triacetylmethyl tomentosate was oxidized to the corresponding ketone (XV) which could be reduced by forced Wolff-Kishner method to give methyl arjunolate (III). The above ketone also suffered isomerization in presence of alkali to give an a,/%unsaturated ketone (XVI). Further, during lactonixation, the acid gives a trihydroxy anhydrolactone (X). The triacetylmethyl ester may be dehydrated using selenium dioxide to give methyldehydro arjunolate (XIX). From these reactions tomentosic acid is tentatively expressed as 2a,3/3,19/7,23-tetrahydroxy-olean-12ene-28-oic acid (XII, R = H).
the twelve Indian Commercial species of Termin&ql T. tomentosa (Indian Laurel), T. belerica,2 and T. panicuZat2 yield commercially important timbers. The heartwood of T. tomentosa, was subjected to successive extraction with petroleum ether, ether and acetone. The petroleum ether extract containc- $-sitostero14 and oleanolic acid5 (VI, R = R, = H) identified as acetates and methyl ester. From the ether extract a sparingly soluble acidic compound C and a more easily soluble neutral compound D were separated (1.5 per cent). The acetone extract furnished the largest percentage of extractives (4.2 per cent) more than 50 per cent of which was insoluble and readily identified as arjunolic acides7 (I) through its methyl ester, bromolactone and other derivatives. The residue was not further examined although the presence of minor components was evident. Compound D, is neutral in character, gives a tetraacetyl derivative; and was shown to be identical with barringtogenol (IV), (isolated from the fruits of Barringtonia racemosa Roxbs-e) by direct comparison and mixed melting point determination with a synthetic sample (IV) obtained by LiAlH4 reduction of methyl arjunolate (III). Compound C was readily recognized by colour reactions as a new triterpene +64”; and named Tomentosic carboxylic acid, Ca,,Hd80,; m.p. 328-330”; (z)(>“,““, OF
* Preliminary communication: Tetrahedron Letters, 27, 12-16, 1960. i R. S. Pearson and H. P. Brown, Commercial Timbers of India pp. 518-524. Govt. of India, Publication Branch, Calcutta (1932). ’ L. R. Row, C. Rukmini and G. S. R. S. Rao, J, Sci. Ind. Rex 20B, 554 (1961). * L. R. Row and G. S. R. S. Rao, Tetrahedron (in press). a R. J. Anderson, R. L. Shriner and G. 0. Burr, J. Amer. Gem. Sot. 48.2987 (1926). L J. C. E. Simpson, J. Chem. Sot. 283 (1944). @F. E. King, T. J. King and J. M. ROSS,J. C/rem. Sot. 3995 (1954). 7Our identification was kindly confirmed by Dr. J. W. W. Morgan, British Celanese Ltd., Nr. Luton by mixed m.p. and I.R. spectral comparison with an authentic sample of arjunolic acid. BR. Anantaraman and K. S. M. Pillai, J. Chem. Sot. 4369 (1956). s F. D. Dodge,J. Amer. Chem. Sot. 40, 1917 (1918). 827
828
L. RAMACHANDRA Row and G. S. R. SUBBA RAO
acid. It was purified through its potassium salt8 followed by chromatography on silica gel and obtained as colourless microprisms which give a Salkowsky’s reaction (colourless to orange pink) useful to distinguish it from arjunolic (I) or terminolic acids (II).
d
HO..
\
COOR
CH,OH
“O..p
Ii
HO
: l-l
HOH,C I, II, m, p,
RI
4-c H
H
\
H
HO HOH,C
R=R,=H R=H’; R,=OH R=Me; RcMe;
R,=H R,=W
Tomentosic acid is a tetrahydroxy triterpene monocarboxylic acid, isomeric but not identical with terminolic acid (II) isolated from Terminalia ivorensis.‘O It yields a readily crystallizable methyl ester, with diazomethane or by the action of dimethyl sulphate on its potassium salt. It is unsaturated (yellow colour with tetranitromethane) and contains a trisubstituted double bond (IR spectrum” of methyl tomentosate izKBr 11.7 ,u (851 cm-l) and 12.2 p (822 cm-l). The methyl ester is resistant to catalytic hydrogenation and to alkaline hydrolysis thus resembling methyl oleanolate (VI) R = Me; R, = H)12 and methyl terminolaterO (V). Further, methyl tomentosate (XII, R = Me) forms an epoxide (VIII R = OH) with mondperphthalic acid or hydrogen peroxide, establishing the presence of a double bond in the molecule. The relative positions of the double bond and carboxyl in tomentosic acid was established by a study of its behaviour towards lactonizing reagents. A stable bromolactone13 (VII; R = OH) is readily formed which resembles closely the bromolactones (VII; R = H) of terminolic and arjunolic acids (II and I). With methanolic potash, an uncrystallizable epoxide (VIII; R = OH) is obtained which may be converted into methyldihydro-lZoxo-tomentosate (IX; R = OH), which is also formed from the epoxide (VIII; R = OH) of methyl tomentosate (XII; R = Me). The epoxide of the bromolactone may be a mixture of a,,4epoxides13 and, therefore, difficult to crystallize. Tomentosic acid closely resembles terminolic acid (II) in the formation of an lo F. I1 A. I* C. I* F.
E. King, T. J. King and J. M. Ross, J. Chem. Sm. 1333 (1955). Meyer, 0. Jeger and L. Ruzicka: Helu. Chim. Acta 33,687 (1950). W. Picard and F. S. Spring, J. Chem. Sm. 1387 (1940). E. King and T. J. King, J. Gem. Sm. 4469 (1956).
829
Chemistry of Terminalia species-VI
anhydrolactone diacetate (X). A molecule of water is lost during lactonization and hence it may be known as anhydrotomentosic lactone (X). Its IR spectrum, lRBr Il.7 ,U (854 cm-‘) and 12.1 ~1 (826 cm-i), reveals the presence of a trisubstituted double bond. Further, it gives a triacetate and not a tetraacetate confirming the loss of a molecule of water between one of the four hydroxyls and a neighbouring activated hydrogen. The view that the lactonization might take place between one of the
&go- f$cooMe-~c Ix
JZIII
PII
4s Id...
0
co
il
XI
hydroxyls and the carboxyl cannot be entertained as the lactone is stable in alkali and also the catalytic hydrogenation resembles that of oleanolic acid isolactone (Xl). The foregoing reactions definitely establish that tomentosic acid must possess the olean-12-en-28-oic acid structure as in arjunolic and terminolic acids (I and II). The co-occurrence of oleanolic acid, arjunolic acid and tomentosic acid in the heartwood of T. tomentosa lends support to this view. The relative distribution of the four hydroxyls in tomentosic acid was studied according to known methods. It yields both a triacetate and a tetraacetate; but the acetyl derivatives are difficult to purify and the melting points were never sharp. The tetraacetate could be secured only with the catalytic assistance of perchloric acid indicating that one of the four hydroxyls is in a sterically hindered position. Methyl tomentosate (XII; R = Me) as well as the anhydrolactone (X), readily give crystalline isopropylidene derivatives suggesting the presence of a 1,3-diol system. Copper pyrolysis yields small quantities of formaldehyde which confirms the presence of a 3,23-diol in the molecule .14 Further, methyl tomentosate (XII; R = Me) gives a positive diosphenol reactiona,lSP1s and the product, after hydrolysis, a violet ferric colouration indicating a 3,23-diol system as in hederagenin. Valuable information regarding the hydroxylic disposition was further gained by the pcriodate and lead tetraacetate oxidation of methyl tomentosate (XII, R = Me), I’ K. Tsuda and S. Kitagawa, Ber. Dtsch. Chem. Ges. 71, 1604 (1938). I6 L. Ruzicka, 0. Jeger and J. Norymbexski, Helu. Chim. Acfa 27, 1185 (1944). lo Carl Djerassi, D. B. Thomas, A. L. Livingstone and C. Ray Thompson, J. Amer. Chem. Sm. 79, 5292 (1957). 2
830
L. RAMACHANDRA Row and G. S. R. SUBBARAO
its anhydrolactone (X) and their isopropylidene derivatives. The methyl tomentosate (XII; R = Me) and the anhydrolactone (X) each require one molar proportion of periodate or lead tetraacetate for oxidation. It is, therefore, presumed that tomentosic acid contains a a&glycol system. I6 As both the isopropylidene derivatives are inert to periodate and lead tetraacetate; the remaining two hydroxyls are not in a glycol system and one of the hydroxyls is common to the a,/?- and 3,23diols. From the foregoing, tomentosic acid must possess a 2a,3b,23(24)-trihydroxy system as in arjunolic and terminolic acids (II and I) and attempts were now made to relate XII with arjunolic acid (II). Oxidation of 2-acetyl-3,23-isopropylidene-methyl tomentosate (XIII) gives a ketone (XIV) which can only be reduced by forced Wolf-Kishner process according to Barton. l7 Removal of the acetyl and isopropylidene groups followed by esterification furnished methyl arjunolate (III) the melting point of which is undepressed by an authentic sample, thus conclusively establishing that tomentosic acid is a hydroxyarjunolic acid (XII; R = H) with all its steric significance.
Evidence for the position of the fourth hydroxyl was principally secured from the reactions of the ketone (XIV) and the anhydrolactone (X). The ketone (XIV) and also the triacetylmethylketo tomentosate (XV) are unreactive towards ketonic reagents showing the sterically hindered character of the ketonic group. Also,. the ketone (XIV) does not give a benzylidene derivative’s indicating the absence of a methylene group a to the carbonyl. Isomerization of XV in the presence of alkali results in the
l7 D. H. R. Barton, D. I. J. Ives and B. R. Thomas, J. C/tern.Sot. 2056 (1955). ‘I D. H. R. Barton, A. J. Head and P. J. May, J. Chem. Sot. 935 (1957).
Chemistry of Terminalia
spies-VI
831
formation of an a,@msaturated ketone (XVI) (31[1=248 rnp, log E, 352). The 12(13) double bond, not originally conjugated to the carbonyl group, has moved to the 13( 18) positions forming an a&unsaturated ketone (XVI).‘O Ruzicka et ~1.‘~observed that the lPketo-methyl oleanolate (as XV) from methyl siaresinolate (VI; R, = OH; R = Me) undergoes similar isomerization with alkali. From this analogy, the fourth hydroxyl in tomentosic acid is probably in the 19th position. The facile dehydration to give the anhydrolactone diacetate (X) may be expected only with hydroxyls at positions 6, 11 and 19. Position 6 is eliminated since triacetylmethylketo tomentosate (XV) is not identical with methyl terminonate (XVII);13 tomentosic acid is not even an epimer of terminolic acid (II). Since the anhydrolactone triacetate (X) cannot be oxidized with Cr,O,-pyridine or even with Cr,O,-HOAc, it may be safely presumed that there is no a-methylene group to the double bond, thus eliminating the 1lth position and also the alternate structure (XVIII) for the anhydrolactone. The fourth hydroxyl can, therefore, only be in the 19th position which further relates tomentosic acid with the only known 1Phydroxytriterpene carboxylic acid, namely siaresinolic acid (VI; R = H; R, = OH), the chief constituent of Siamese gum benzoin.20 The lPhydroxy1 in tomentosic acid should be capable of dehydration as in siaresinolic acidzl to give methyldehydroarjunolate (XIX). No methyldehydro arjunolate could be obtained from triacetylmethyltomentosate (XII, R = Me) on reflexing with POCl,-pyridine, but dehydration did occur giving an isomeric compound which may be termed methylanhydrotomentosate. The latter contained an easily reducible double bond not conjugated with the 12( 13) double bond as determined from the U.V. absorption spectrum which has a single peak at 216 rnp. Attempts were next made to dehydrate methyl tomentosate with other reagents like P,O,-benzene and selenium dioxide .22 Under varying conditions the former reagent With selenium dioxide only resins were gives only methylanhydrotomentosate. obtained when refluxed for 10-20 hr in acetic acid medium, but as in every experiment metallic selenium was deposited in the first 10-15 minutes, if the reaction was terminated after 15 minutes, methyldehydroarjunolate (XIX) was secured in quantitative yield. The use of selenium dioxide as a dehydrating agent is reported in the literature only in the case of a triterpenoid, jaegosapogenol,a2 whose constitution is still unsettled. The mechanism of this dehydration is obscure but solvolysis of the selenous acid ester may take place. Similar dehydration was affected with the pcntol-tetraacetate (XX, R = AC), obtained by the lithium aluminium hydride reduction of methyl tomentosate (XII, R = Me). The dehydro derivative was found to be identical with tetraacetyldehydrobarringtogenol (XXI) which was obtained by selenium dioxide dehydrogenation of barringtogenol (tetraacetate). Thus tomentosic acid (XII R = H) behaves differently with POCl,-pyridine and with selenium dioxide giving rise to two isomeric anhydro compounds. The formation of dehydroarjunolate conclusively establishes the 19th position for the fourth hydroxyl. It is evident, that the steric configuration of the 19th hydroxyl must differ from that in I’ L. Ruzicka, A. Grob, R. Egli and 0. Jeger, Heh. Chin. Acta 26, 1218 (1943). *OP. Bilham, G. A. R. Kon and W. C. J. Ross, J. Chem. Sot. 540 (1942). *I D. H. R. Barton and N. J. Holness, J. Chem. SIC. 78 (1952). ** S. Tobinaga, Chem. Ahrr. 52, 13686 (1958).
L. RAMACHANDRARow and G. S. R. SUBBA RAO
832
siaresinolic acid in which the 19th hydroxyl is a-axial and being truns situated to 18(/3)H, it readily suffers dehydration. Obviously, therefore, in tomentosic acid, the
PcOH,d
4cOHc,d ’
~
XEI
xx
19th hydroxyl must have the epimeric @-equatorial configuration which alone can explain the formation of a new anhydrotomentosic acid with POCl,-pyridine. The course of dehydration with this reagent requires further study which is in progress. Tentatively, however, tomentosic acid may be expressed as 2a,3/3,19,!I,23-tetrahydroxyolean-12-ene-28-oic acid (XII, R = H). EXPERIMENTAL M.P,s are uncorrected. Optical rotations were measured in chloroform unless otherwise stated and the IN absorption spectra recorded in ethanol. The compounds described were all purified by chromatographic adsorption on alumina and before analysis, dried at 100”/0.2 mm for 6 hr. Exrruclion of the hearrwood
of Terminalia tomentosa
The powdered wood (2 kg) was extracted successively with pet ether (b.p. W), ether and acetone. Colourless crystalline solids separated out during extraction with ether and acetone necessitating their removal and pursuing the extraction with fresh solvent. Petrofeum ether exfrucl. The pale yellow extract, when concentrated to 200 ml deposited a light yellow solid (compound A m.p. 260-290” ; 0.75 g). From the filtrate, all the solvent was removed and the thick orange yellow oil slowly deposited a colourless solid (compound B; 0.5 g). Ether extract. During the extraction, a colourless crystalline compound (31.5 g) separated. It was removed by filtration and evaporation of the filtrate deposited an additional 22.0 g of the compound. The total solids (53.5 g) were refluxed with acetone (2 1.) and the undissolved material (m.p. 332-334”; 5 g) remobcd by filtration. Evaporation of the filtrate afforded a pale yellow mass which was dissolved in 4”/, methanolic KOH and extracted continuously with ether in a liquid-liquid extractor. The dried ether extract on evaporation yielded a small amount (I .2 g) of the neutral fraction (compound D; m.p. 260-280”). The alkaline layer was acidified with dil HCl (Congo red) and the precipitate after several crystallizations from anhydrous acetone yielded 21 g of a colourless solid (compound C, m.p. 320-324”). Acetone extract. The solid (compound E, 90 g) after 3 crystallizations from acetone yielded microprisms, m.p. 332-334”. The filtrate from compound E deposited impure brown solid. Compound
A
Oleunolic acid. Compound A is soluble in aq. Na,CO, and aq. NaOH and was purified through its potassium salt and crystallized from methanol as needles (0.1 g); m.p. 306309”; (&,‘“, +76” (c, 1.05). Lit0 m.p. 306308”. (Found: C, 78.7; H, 10.4; CSOHIBOSrequires: C, 78.9; H, 10.6%). Methyl oleunolure (diazomethane) crystallized from methanol as irregular plates, m.p. 200-202”, (&,“, -1-70”(c, 1.0). Lit.’ m.p. 204”. (Found: C, 78.82; H, 10.51; OMe, 6.3; C,,H,,O, requires: C, 79.15; H, 1064; OMe, 6.6%). Acetate (acetic anhydride-pyridine) crystallized from acetone-pet ether as colourless prisms, m.p. 260-261”. (Found: C, 77.02; H, 1@4; C,,H,,O, requires: C, 77.10; H, IO.1 %).
Chemistry of Termtitaiia species-VI
833
Compotmd B /?-sitosterol. Compound B, after two crystallizations from methanol separated as prismatic needles m.p. 136-137”. (a)“,‘” -35” (c, 1.5) Lit.’ m.p. 136137”, (ah, -35”. (Found: C, 83.78; H, 1240; C,,H,,O requires: C, 8404; H, 12.08%). /?-sitosterof acetate (acetic anhydride-pyridine) crystallized as needles from methanol m.p. 126 127”; (u)“d”. -38” (c, 2.2). Lit.*m.p. 126127”; (a)n - 35”. (Found: C, 81.3; H, 10.8; C,,H,,O, requires: C, 81.5; H, 11.5%). Compound C Tomentosic acid (XII, R 7 H). Compound C was dissolved in 2N methanolic KOH and the sparingly soluble potassium salt continuously extracted with ether. After decomposition with dil HCI (Congo red), the product was crystallized from acetone as micro prisms m.p. 328-330” (a):“, +64” (c, 0.32 in ethanol). A sample (100 mg) of the acid in acetone (30 ml) was eluted from a column of silica gel (8 g) with benzene-methanol (1: 1; 200 ml) and after evaporation of solvent, the residue crystallized from anhydrous methanol as colourless prisms, m.p. 328-330’. (Found: C, 71.8; 71.7; H, 9.3, 9.6; C,,H,*O, requires: C, 71.4 and H, 9.5%). The acid is readily soluble in acetic acid, pyridine and sparingly soluble in organic solvents. In cone H,SO, it changes from colourless to orange pink, and exhibits a pale yellow colour with tetranitromethane. Methyl tomentosate (XII, R = Me). Tomentosic acid (I g) in methanol (20 ml) was treated with ethereal diazomethane. Next day, the ether was removed and the residue crystallized from methanol as colourless prisms m.p. 218-220”. A solution of the methyl ester (100 mg) in dry benzene (20 ml) was chromarographed on alumina. It was eluted with ether-methanol (3: 1). Evaporation of the solvent and two crystallizations from methanol gave the methyl ester as colourless needles; m.p. 221-222”; (a)r, +72” (c, 0.53). (Found: C, 71.4; H, 9.6; OMe, 6.3; C,,H,,O, requires: C, 71.8, H, 9.6 and OMe, 6.2%). AcetyIation of tomentosic acid Tomentosic acid (1 g) in acetic anhydride (5 ml) and dry pyridine (5 ml) was allowed to stand I2 hr and then diluted with water. The triacetate (0.85 g) after crystallization from methanol and acetone yielded an amorphous powder with a m.p. of 168-186”. Chromatographic purification over alumina did not improve the crystalline nature, nor the m.p. (Found: C, 68.8, H, 8.65 OAc, 18.2 C,,H,,O, requires: C, 68.6; H, 8.57; 3-OAc 20.46%). Tomentosic acid (I g) was suspended in acetic anhydride (5 ml) and a drop of perchloric acid added. There was an immediate rise in temp and discoloration of the solution. This was poured into water and the tetraacetate crystallized as above as an amorphous powder. (Found: C. 67.5; H, 8.5; OAc, 22.9, C,,H,,O,, requires: C, 67.86; H, 8.33; 4-OAc, 25.5%). Tomentosic bromolactone (VII, R = OH) To a mixture of tomentosic acid and sodium acetate (0.5 g) dissolved in 10 ml acetic acid, a solution of bromine in acetic acid (4%. 10 ml) was added drop by drop while shaking. After 1 hr, the reaction mixture was poured into water (50 ml) containing sodium thiosulphate and the bromolactone which separated crystallized from methanol as colourless needles, m.p. 234-236”; (a):“, $-45” (c. 1.48) (Found: C, 61.5; H, 8.8; C,,H,,O,Br requires: C, 61.7 and H, 8.1 %). Methy/ 12,13-epoxy-tomentosate (VIII, R = OH) Methyl tomentosate (500 mg) in ether-dioxan (3: I, 40 ml) was treated with ethereal monoperphthalic acid (6 ml; 0.57N) and kept at 0” for 17 days. The mixture was then washed with N/4 NaOH and dried over potassium carbonate. Removal of the solvent furnished a colourless residue which after two crystallizations from methanol gave methyl 12,13epoxy tomentosate as colourless cubes (320 mg) m.p. 158-160”; (a)g”, t-18” (c. 1.5) (Found: C, 69.2; H. 9.5; C,,H,,O, requires: C, 69.6; H, 9.4%). Methyldihydro-12-oxo tomentosate (IX, R = OH) (a) A solution of the epoxide (0.75 g) in acetic acid and a trace of 10% HCI was heated on a
834
L. RAMACHANDRARow and G. S. R. SUBBA RAO
steam bath for 8 hr, diluted with water and the product which could not be crystallized was subjected to hydrolysis with 4% methanolic KOH. The methyl dihydro-12-oxo tomentosate crystallized from methanol in needles (0.25 g); m.p. 196-197”: (a)z”, -32” (c, 1.25) (Found: C, 69.92; H, 9.5, C,,H,,O, requires: C, 69.6 and H, 9.4%). (b) A solution of methyl tomentosate tetraacetate in acetic acid and 30 % H,O, (1 ml) was heated on a water bath at 100” for 8 hr. The reaction mixture was poured into water and extracted with ether. Evaporation of the dried ether extract afforded a gum which was deacetylated by refluxing with 50 ml 4% methanolic KOH for 1 hr. The dihydro-oxo-ester (0.25 g) was crystallized from methanol as small prisms, m.p. 196197”, undepressed with the sample obtained above. Hydrolysis of tomentosic bromolactone Methyldihydro-12-oxo-tomentosate (IX, R = OH). Tomentosic bromolactone (1 g) was refluxed with 3 ‘A KOH for 1 hr. It was poured into water and as the precipitate failed to crystallize. it was isomer&d by dissolving in chloroform and saturating with dry HCI at room temp. Removal of the solvent and crystallization from methanol gave methyl dihydro-12-oxo tomentosate, m.p. 192-196”; (a)=, -30” (c, 1.6) undepressed by the sample obtained above. (Found: C, 69.5; H, 9.8; CtlHIDO, requires: C, 69.6 and H, 9.4%). Anhyako tomentosic lactone diacetate Tomentosic acid (5 g) was dissolved in 50% HRr-HOAc and after 48 hr at room temp, the purplish red solution was diluted with water. The precipitated anhydro tomentosic lactone diacetate crystallized from methanol in needles, m.p. 233-235”; (a$“, -20” (c, 15). The W absorption gave IBfb6”01210 m&log E, 3.12) and 220 mu (log E 2.53). The IR spectrum showed characteristic bands a7.Y,mr 2.97 p (3368 cm-r for OH), 5.67 y. 5.76 p (1764 cm-l, 1736 cm-l) for lactone, 1 l-63 p (860 cm-l) and 12.02 ~c (834cm-r) for a trisubstituted double bond (Found: C, 71.6, H, 8.5, OAc, 11.4; C,,H,,O, requires: C, 71.6, H, 8.6 and 2-OAc, 15X@%). The lactone diacetate gave no colour with tetranitromethane. Anhydrotomentosic lactone (X) Anhydrotomentosic lactone diacetate (1.2 g) was refluxed with 4% methanolic KOH. After 4 hr it was poured into water and continuously extracted with ether. The dried ether extract, on removal of the solvent, gave a pale yellow mass which crystalked from acetone in small prisms (0.85 g); m.p. 340-342”, (a~):~, -9” (c, O-4) (Found: C, 73.68; H, 9.87; CloHIIOI requires: C, 74.0 and H, 9.5 %). The compound gave no colour with tetranitromethane and has the UV absorption at cz 210 rnp (log E. 3.12) and 220 rnp (log e, 2.50). Anhydrotomentosic lactone triacetate Anhydrotomentosic lactone or its diacetate was acetylated with acetic anhydride and a trace of perchloric acid. The M-acetate crystallized from methanol as colourless plates, m.p. 250-252”; (a)tW, +1*8” (c, 1.5) (Found: C, 69.98; H, 8.97, CIIH5,0s requires: C, 70.55 and H, 8*55”%). O,@isopropylidkne-anhydrotomentosic lactone Anhydrotomentosic lactone (500 mg) in 25 ml dry acetone was treated with a drop cone HCI. The lactone dissolved and deposited the isopropylidene derivative which crystallized from aqueous acetone (450 mg) as colourless transparent prisms; m.p. 319-320”. (a)r, + 8” (c, 0.52) (Found: C, 74.8; H, 9.8; C,,H,,O, requires: C, 75.2 and H, 9.6%). Anhyaio-epoxy-tomentoosic lactone triacetate Anhydrotomentosic lactone triacetate (1.0 g) in acetic acid (20 ml) was treated with 30 % hydrogen peroxide (1 ml) and the mixture heated at 100” for 3 hr. The product was isolated by dilution with water followed by crystallization from methanol giving the anhydro-epoxy-tomentosic lactone - 18” (c, 0.96) (Found : C. 68.5 ; H, triacetate as colourless plates (600 mg) m.p. 270-272”; (ar 8.45; C,,H,,O, requires: C, 68.8 and H, 8.28 “/,).
Chemistry of Terminalia species-VI
835
O,O+opropyli&ne methyl tomentosate Methyl tomentosate (100 mg) was suspended in dry acetone (10 ml) and treated with a drop of cont. HCI. After 12 hr at o”, the solution was poured into dil ammonium hydroxide solution and extracted with ether. The dried ether extract on evaporation gave a semisolid which crystallized from +68” (c, 1.2) (Found: C, 735; H, 9.9; CIIHI,OI acetone in prisms (70 mg) m.p. 168-170”; (a)r, requires: C, 73.1 and H, 9.7%). Pyrolytic experiments A mixture of tomentosic acid (1 g) and finely divided copper (5 g) was heated to 270-290” for 1 hr, while passing a stream of carbon dioxide. The evolved gases were passed into a saturated solution of dimedone. The precipitate (20 mg) was collected and crystallized from alcohol as colourless needles, m.p. 186-189”. undepressed by an authentic formaldehyde dimedone derivative. Similar experiments with methyl tomentosate and anhydrotomentosic lactone also gave formaldehyde. Oxidation with soa%m metaperiodate (a) Methyl tomentosate. An ethanolic solution of methyl tomentosate (200 mg) was treated with aqueous sodium metaperio-date (10 ml; O*lN), the vol made up to 50 ml with ethanol and the solution kept in the dark at room temp. Aliquot portions (10 ml each) were removed after &2), 4 and 24 hr. The excess of periodate was estimated using standard sodium arsenite solution. The compound absorbed 0.41,0.82.0.87 and 099 moles of periodate respect,ively showing the presence of a,&glycol system in the molecule. (b) O,O-isopropylidenemethyl tomentosate. Isopropylidenemethyl tomentosate (100 mg) was treated with excess of sodium metaperiodate and quantitative estimations as before, showed no oxidation. The compound was recovered unchanged after 24 hr. (c) Anhydrotomentosic lactone. Anhydrotomentosic la&one (100 mg) was treated with excess of sodium metaperiodate (8 ml; O.lN). The estimation was carried out as before and the oxidation corresponded to 36, 80, 88 and 99 % of 1,Zglycol unit. (d) O,O-Isoprypylidene-anhydrotomentosic lactone. Isopropylidene-anhydrotomentosic lactone (100 mg) did not react with aqueous sodium metaperiodate. Oxidation of methyl tomentosate with lead tetraacetate Methyl tomentosate (100 mg) was dissolved in A.R. acetic acid (20 ml) and was treated with 15.2 times the molar excess of lead tetraacetate. Periodically in 10 ml samples the excess lead tetraacetate was estimated iodometrically. The rate constants for the oxidiaton were calculated according to the method of Cordner and Pausacker.= The oxidation of methyl tomentosate was completed in 14 hr and the rate constant was found to be K = 1.3 x 10-l lit. mol-’ se& thus corresponding to an a,&glycol system in the molecule. 2-Acetyl-3,23-isopropyIidenemethyl tomentosate (XIII) 3,23-Isopropylidenemethyl tomentosate was acetylated with acetic anhydride and pyridiie. The acetate failed to crystallize from methanol and separated as amorphous powder. (Found: C, 71.8; H, 9.8; C,,H,,O, requires: C, 72.0 and H, 9.4%). 2-Acetyl-3,23-isopropylidene-19-keto-methyl
tomentosate (XIV)
The above acetate (1.0 g) in dry pyridine (20 ml) was added to pyridinechromic anhydride (10 ml containing 05 g Cr,OS) at room temp. The orange Cr,O,) complex rapidly disappeared with precipitation of a dark brown product. After 2 hr, it was filtered off, washed with pyridine and the filtrate poured into water (200 ml). This was extracted with ether and evaporation of the dried ether extract resulted in a gum which was purified (alumina) and recrystallized from methanol as needles, m.p. 204-205”; (a),““, +20” (c, 1.2) (Found: C, 71.9; H, 9.4; C,H,,O, requires: C, 72.25 H, 9-03”/,). 3,23-lsopropyliabe-19-keto-methyl
tomentosate
3,23Isopropylidenemethyl tomentosate (1 .Og) was similarly oxidized with pyridine and chromic acid at room temp yielding 3,23_isopropylidene 19-keto-methyl tomentosate as stout needles (0.7 g) *8 J. P. Cordner and K. H. Pausacker, J. Chem. Sot. 102 (1953).
836 m.p. 228-230”. (z)r, H, 9.35 “/,).
L RAMACHANDRARow and G. S. R. + 38’ (c. 1.04) (Found:
SUBBA RAO
C, 72.5; H, 9.25; C,,H,,O,
requires:
C, 73.38 and
Merhyl-19-keto-tomentosare Similar oxidation of methyl tomentosate with excess of chromium trioxide and pyridine (4 moles) gave methyl-19-keto tomentosate which crystallized from methanol as prisms (120 mg) m.p. 269-270”; (IL%‘, i-40” (c, 1.2) (Found: C, 72.8; H, 9.4: C,,H,,O, requires: C, 72.88 and H, 9.3%). Reduction of 2-acetyl-3,23-isopropylidene-19-kero-merhyl tomer.tosate to methyl arjunokate (III) Sodium (0.2 g) in diethylene glycol(l0 ml) was heated to 180”. anhydrous hydrazine (4 ml) added and the mixture refluxed at 180”. 2-Acetyl-3,23-isopropylidene 19-keto-methyl tomentosate (I g) in ethylene glycol was added quickly and the solution refluxed for 12 hr. The temperature was then raised to 210” and the solution refluxed at this temp for 24 hr. The reaction mixture was then poured into water and the precipitate collected. Removal of the isopropylidene and acetyl groups and esterilication with ethereal diazomethane afforded a gum which was purified by chromatography on alumina. Elution with ether-methanol (3: 1) and crystallization from methanol deposited the methyl arjunolate (100 mg) as needles, m.p. 205-207”; (a)r, $67” (c. 0.5) undepressed by an authentic sample of methyl arjunolate. (Found: C, 73.82; H, 9.81; C,,H,,O, requires: C, 74.10 and H, 9.96%). The modified Wolff-Kishner reduction with both 3,23-isopropylidene-19-keto methyl tomentosate and triacetylmethyl-19-keto tomentosate also afforded methyl arjunolate (Ill). Selenium dioxide oxidation of methyl tomentosale tetraacetate A solution of tetraacetylmethyl tomentosate (0.8 g) in A.R. acetic acid (50 ml) containing resublimed selenium dioxide (0.4 g) was heated under reflux for 17 hr. After removal of metallic selenium, the solvent was evaporated under red press. The brown residue was dissolved in ether, washed with sodium bicarbonate and dried. Removal of the solvent afforded a glassy mass which failed to crystallize but showed the characteristic UV absorption iEtxu, 243 m,u (log E, 4.21). 251 rnp (log E, 4.31) and 260 m/d (log E, 4.10). Hydrolysis of the above residue with 20% methanolic potash did not afford any crystalline material.
Triacetyl methyl-19-kero tomenfosate (xv) Triacetylmethyl tomentosate (1 g) in pyridine (6 ml) was added to Cr,O,-pyridine complex (10 ml, containing 0.5 g Cr,O,) at room temp. After 1 hr the brown precipitate was filtered off and the filtrate diluted with water. The precipitate was collected and separated from acetonepet ether as an amorphous powder (0.6 g) which has the UV absorption ct: 292 rnp (log E, 1.92). (Found: C, 68.5; H, 8.6; C,,H,,O, requires: C, 69.16 and H, 8.41%). Methyl 2,3,23-trihydroxy-olean-13-en-28-oate (XVI) Triacetyl-lPketo-tomentosate (0.4 g) was refluxed with 2N methanolic KOH for 4 hr. The reaction mixture was poured into water, extracted with ether and the dried ether extract on evaporation gave a glassy residue. This crystallized from acetone in small prisms (0.2 g) m.p. 238-240 (ak”, -13” (c, 1.09). The compound has the UV absorption A”,:9” 248 rnp (log E, 3.52) (Found: C, 72.3; H, 9.45; C,,H,,O, requires: C, 72.1 and H, 9.3%). Methyldehydro arjunolate (XIX) Triacetylmethyl tomentosate (800 mg) in A.R. acetic acid (20 ml) containing a little acetic anhydride (1 ml) was heated to boiling with selenium dioxide (100 mg). After 10 min and removal of metallic selenium the filtrate was diluted with water and hydrolysed with 2N methanolic alkali. The methyldehydro arjunolate crystalltid as colourless needles from methanol (180 mg) m.p. 250-251”; (a)‘,““, - 150” (c, 1.25) undepressed by admixture with an authentic sample. It has the triple U.V. C, 74.3; H, 9.9, C,,H,,O, absorption A,,, 243, 252, 261 rnp (log c, 4.33, 4.38, 4.19) (Found: requires: C, 74.4 and H, 9.6 %).
Chemistry of Terminaliu species--VI Reduction
of methyl
837
with LiAlH,
tomentosate
To a suspension of LiAIHI (1 g) in dry ether (200 ml) in an atmosphere of nitrogen, an ethereal solution of methyl tomentosate (1.0 g; 50 ml) was added dropwise. The mixture was stirred for 2 hr, left overnight and then decomposed by addition of ice cold dil H$O, and extracted with ether. The dried ether extract, on evaporation gave a glassy residue. The pentahydroxy-carbinol (XX) crystallized from methanol in prisms (200 mg) m.p. 280-282”, (a)‘,““, +50” (c, 1.5 in ethanol) (Found: C, 73,57, H, 10.5; C,&,O, requires: C, 73.46 and H, 10.2%). Terraacetate (XX). The tetraacetate (A@-pyridine) of the penrahydroxy compound crystallized from methanol in long needles m.p. 265-266”; (a):“, -I 42 (c, @3). Dehydrobarringtogenol
tetraacetate
(XXI)
The above tetraacetate (70 mg) in A.R. acetic acid was refluxed as before with selenium dioxide (40 mg). The dehydro compound was purified (alumina) and crystallized from methanol in needles m.p. 196-197”; (a):’ -72” (c, 0.8) unchanged by an authentic sample of dehydrobarringtogenol tetraacetate.* (Found: C, 71.5; H, 8.9; Ca,,H,,Os requires: C, 71.2 and H, 8.8%). Examination
of compound
D
(IV). The neutral fraction from the ether extract crystallized from acetone as microprisms m.p. 289-290” ; (a) p, f22” (c, 0.8 in ethanol). This was undepressed by a sample obtained by LiAIHI reduction of methyl arjunolate. (Found: C, 75.8; H, 10.5; C,,H,,O, requires: C, 75.95 and H, 10.55 %). The compound gave a cherry red solution in sulphuric acid; Liebermann-Burchard’s reaction, pink rapidly changing to violet with strong fluorescence. Anantaraman et al. recorded for barringtogenol, m.p. 290-291”; (ah,, +18”. Burriqtogenol
Reduction
of methyI arjunolate
with LiAIHS
Barringtogenol (IV). To a suspension of LiAIHl (200 mg) in dry ether (200 ml) was added dropwise, while stirring in an atmosphere of nitrogen, an ethereal solution of methyl arjunolate (200 mg) and the mixture left overnight. After 24 hr, ice-cold water (200 ml) containing a little H,SO, was slowly added and the ether layer separated and dried. Removal of the solvent afforded a colourless gum which was crystallized from acetone, yielding barringtogenol as micro prisms (110 mg) m.p. 290-291”; (a):“, j-20” (c, 1.8 in ethanol) (Found: C, 75.63; H, 10.8; C,,H,,O, requires: C, 75.95 and H, 10.55%). Acetate. (Acetic anhydride-pyridine) crystallized from methanol as small needles m.p. 268-270”; (Found: C, 70.85; H, 9.5; (a) 2,” + 18” (c. 1.2) undepressed by barringtogenol tetraacetate. C,,H,,O, requires: C, 71.0 and H, 9.0%). Examination
of compound
E
Compound E crystallized from a large volume of acetone as shining microprisms, m.p. 332-336” (a):“, +63” (c, 0.51 in ethanol) (Found: C, 73.67, H, 9.47; C,,H,,O, requires: C, 73.77 and H, 9.9%). The compound dissolves in cone H,SO, to give a yellow solution changing to red; LibermannBurchard’s reaction pink changing to reddish brown and developed a faint yellow colour with tetranitromethane. King et a1.O record for arjunolic acid m.p. 337-240”; (ah,, $63.5”. Methyl arjunolafe (III). Compound E was methylated with excess of ethereal diazomethane. The methyl ester crystallized from methanol as colourless needles m.p. 209-211”; (a)r, +68” (c, 2.2) (Found: C, 73.8; C, H, 10.2, C,,H,,O, requires: C, 741 and H, 10.0%). Arjunolic
acid (I).
Arjunolic bromolactone
A solution of the compound E (100 mg) and sodium acetate (200 mg) in acetic acid (4 ml; 90%) was stirred during dropwise adddition of 4 ‘A bromine in acetic acid (5 ml). After 1 hr, the mixture was poured into water containing sodium thiosulphate, the precipitate collected and crystallized from methanol. The bromolactone separated as colourless needles (120 mg) m.p. 24W, (a)$“, +53” (c, 1.2). (Found: C, 63.4, H, 8.1; C,,H,,O, Br requires: C, 63.5 and H, 8.3%); Lit.’ m.p. 240-244’.
838
L.
RAMAC?iANDRA
Row and G. S. R.
SIJLIBARAO
Ackrwwfe&ements-Our thanks are due to Prof. F. E. King, F.R.S., and J. W. W. Morgan for kindly confirming our identification of arjunolic acid, to the Director, National Physical Laboratory, New Delhi, for the I.R. Spectra and to Prof. T. R. Seshadri, F.R.S., for the UV absorption spectral data. One of us (G. S. R.) wishes to express his grateful thanks to the Council of !kientific & Industrial Research, New Delhi, for a fellowship.
1962. Vol.
18. pp. 827 to 838.
CHEMISTRY
l’er@mon
Prca
Ud.
Phted
In North
OF TERMINALIA
Imhnd
SPECIES-VI
THE CONSTITUTION OF TOMENTOSIC ACID, A NEW TRITERPENE CARBOXYLIC ACID FROM TERMINALIA TOMENTOSA WIGHT ET ARN” L. RAMACHANDRA Row and G. S. R. SUBBA RAO Department of Chemistry, Andhra University, Waltair, India (Receiued 1 February 1962) Abstract-From the heartwood of T. tomentusu Wight et Am, /?-sitosterol, oleanolic acid (VI, R = R, = H), arjunolic acid (I) and barringtogenol (IV) were isolated and in addition a new tetrahydroxy triterpene mono-carboxylic acid, now named Tomentosic acid. The triacetylmethyl tomentosate was oxidized to the corresponding ketone (XV) which could be reduced by forced Wolff-Kishner method to give methyl arjunolate (III). The above ketone also suffered isomerization in presence of alkali to give an a,/%unsaturated ketone (XVI). Further, during lactonixation, the acid gives a trihydroxy anhydrolactone (X). The triacetylmethyl ester may be dehydrated using selenium dioxide to give methyldehydro arjunolate (XIX). From these reactions tomentosic acid is tentatively expressed as 2a,3/3,19/7,23-tetrahydroxy-olean-12ene-28-oic acid (XII, R = H).
the twelve Indian Commercial species of Termin&ql T. tomentosa (Indian Laurel), T. belerica,2 and T. panicuZat2 yield commercially important timbers. The heartwood of T. tomentosa, was subjected to successive extraction with petroleum ether, ether and acetone. The petroleum ether extract containc- $-sitostero14 and oleanolic acid5 (VI, R = R, = H) identified as acetates and methyl ester. From the ether extract a sparingly soluble acidic compound C and a more easily soluble neutral compound D were separated (1.5 per cent). The acetone extract furnished the largest percentage of extractives (4.2 per cent) more than 50 per cent of which was insoluble and readily identified as arjunolic acides7 (I) through its methyl ester, bromolactone and other derivatives. The residue was not further examined although the presence of minor components was evident. Compound D, is neutral in character, gives a tetraacetyl derivative; and was shown to be identical with barringtogenol (IV), (isolated from the fruits of Barringtonia racemosa Roxbs-e) by direct comparison and mixed melting point determination with a synthetic sample (IV) obtained by LiAlH4 reduction of methyl arjunolate (III). Compound C was readily recognized by colour reactions as a new triterpene +64”; and named Tomentosic carboxylic acid, Ca,,Hd80,; m.p. 328-330”; (z)(>“,““, OF
* Preliminary communication: Tetrahedron Letters, 27, 12-16, 1960. i R. S. Pearson and H. P. Brown, Commercial Timbers of India pp. 518-524. Govt. of India, Publication Branch, Calcutta (1932). ’ L. R. Row, C. Rukmini and G. S. R. S. Rao, J, Sci. Ind. Rex 20B, 554 (1961). * L. R. Row and G. S. R. S. Rao, Tetrahedron (in press). a R. J. Anderson, R. L. Shriner and G. 0. Burr, J. Amer. Gem. Sot. 48.2987 (1926). L J. C. E. Simpson, J. Chem. Sot. 283 (1944). @F. E. King, T. J. King and J. M. ROSS,J. C/rem. Sot. 3995 (1954). 7Our identification was kindly confirmed by Dr. J. W. W. Morgan, British Celanese Ltd., Nr. Luton by mixed m.p. and I.R. spectral comparison with an authentic sample of arjunolic acid. BR. Anantaraman and K. S. M. Pillai, J. Chem. Sot. 4369 (1956). s F. D. Dodge,J. Amer. Chem. Sot. 40, 1917 (1918). 827
828
L. RAMACHANDRA Row and G. S. R. SUBBA RAO
acid. It was purified through its potassium salt8 followed by chromatography on silica gel and obtained as colourless microprisms which give a Salkowsky’s reaction (colourless to orange pink) useful to distinguish it from arjunolic (I) or terminolic acids (II).
d
HO..
\
COOR
CH,OH
“O..p
Ii
HO
: l-l
HOH,C I, II, m, p,
RI
4-c H
H
\
H
HO HOH,C
R=R,=H R=H’; R,=OH R=Me; RcMe;
R,=H R,=W
Tomentosic acid is a tetrahydroxy triterpene monocarboxylic acid, isomeric but not identical with terminolic acid (II) isolated from Terminalia ivorensis.‘O It yields a readily crystallizable methyl ester, with diazomethane or by the action of dimethyl sulphate on its potassium salt. It is unsaturated (yellow colour with tetranitromethane) and contains a trisubstituted double bond (IR spectrum” of methyl tomentosate izKBr 11.7 ,u (851 cm-l) and 12.2 p (822 cm-l). The methyl ester is resistant to catalytic hydrogenation and to alkaline hydrolysis thus resembling methyl oleanolate (VI) R = Me; R, = H)12 and methyl terminolaterO (V). Further, methyl tomentosate (XII, R = Me) forms an epoxide (VIII R = OH) with mondperphthalic acid or hydrogen peroxide, establishing the presence of a double bond in the molecule. The relative positions of the double bond and carboxyl in tomentosic acid was established by a study of its behaviour towards lactonizing reagents. A stable bromolactone13 (VII; R = OH) is readily formed which resembles closely the bromolactones (VII; R = H) of terminolic and arjunolic acids (II and I). With methanolic potash, an uncrystallizable epoxide (VIII; R = OH) is obtained which may be converted into methyldihydro-lZoxo-tomentosate (IX; R = OH), which is also formed from the epoxide (VIII; R = OH) of methyl tomentosate (XII; R = Me). The epoxide of the bromolactone may be a mixture of a,,4epoxides13 and, therefore, difficult to crystallize. Tomentosic acid closely resembles terminolic acid (II) in the formation of an lo F. I1 A. I* C. I* F.
E. King, T. J. King and J. M. Ross, J. Chem. Sm. 1333 (1955). Meyer, 0. Jeger and L. Ruzicka: Helu. Chim. Acta 33,687 (1950). W. Picard and F. S. Spring, J. Chem. Sm. 1387 (1940). E. King and T. J. King, J. Gem. Sm. 4469 (1956).
829
Chemistry of Terminalia species-VI
anhydrolactone diacetate (X). A molecule of water is lost during lactonization and hence it may be known as anhydrotomentosic lactone (X). Its IR spectrum, lRBr Il.7 ,U (854 cm-‘) and 12.1 ~1 (826 cm-i), reveals the presence of a trisubstituted double bond. Further, it gives a triacetate and not a tetraacetate confirming the loss of a molecule of water between one of the four hydroxyls and a neighbouring activated hydrogen. The view that the lactonization might take place between one of the
&go- f$cooMe-~c Ix
JZIII
PII
4s Id...
0
co
il
XI
hydroxyls and the carboxyl cannot be entertained as the lactone is stable in alkali and also the catalytic hydrogenation resembles that of oleanolic acid isolactone (Xl). The foregoing reactions definitely establish that tomentosic acid must possess the olean-12-en-28-oic acid structure as in arjunolic and terminolic acids (I and II). The co-occurrence of oleanolic acid, arjunolic acid and tomentosic acid in the heartwood of T. tomentosa lends support to this view. The relative distribution of the four hydroxyls in tomentosic acid was studied according to known methods. It yields both a triacetate and a tetraacetate; but the acetyl derivatives are difficult to purify and the melting points were never sharp. The tetraacetate could be secured only with the catalytic assistance of perchloric acid indicating that one of the four hydroxyls is in a sterically hindered position. Methyl tomentosate (XII; R = Me) as well as the anhydrolactone (X), readily give crystalline isopropylidene derivatives suggesting the presence of a 1,3-diol system. Copper pyrolysis yields small quantities of formaldehyde which confirms the presence of a 3,23-diol in the molecule .14 Further, methyl tomentosate (XII; R = Me) gives a positive diosphenol reactiona,lSP1s and the product, after hydrolysis, a violet ferric colouration indicating a 3,23-diol system as in hederagenin. Valuable information regarding the hydroxylic disposition was further gained by the pcriodate and lead tetraacetate oxidation of methyl tomentosate (XII, R = Me), I’ K. Tsuda and S. Kitagawa, Ber. Dtsch. Chem. Ges. 71, 1604 (1938). I6 L. Ruzicka, 0. Jeger and J. Norymbexski, Helu. Chim. Acfa 27, 1185 (1944). lo Carl Djerassi, D. B. Thomas, A. L. Livingstone and C. Ray Thompson, J. Amer. Chem. Sm. 79, 5292 (1957). 2
830
L. RAMACHANDRA Row and G. S. R. SUBBARAO
its anhydrolactone (X) and their isopropylidene derivatives. The methyl tomentosate (XII; R = Me) and the anhydrolactone (X) each require one molar proportion of periodate or lead tetraacetate for oxidation. It is, therefore, presumed that tomentosic acid contains a a&glycol system. I6 As both the isopropylidene derivatives are inert to periodate and lead tetraacetate; the remaining two hydroxyls are not in a glycol system and one of the hydroxyls is common to the a,/?- and 3,23diols. From the foregoing, tomentosic acid must possess a 2a,3b,23(24)-trihydroxy system as in arjunolic and terminolic acids (II and I) and attempts were now made to relate XII with arjunolic acid (II). Oxidation of 2-acetyl-3,23-isopropylidene-methyl tomentosate (XIII) gives a ketone (XIV) which can only be reduced by forced Wolf-Kishner process according to Barton. l7 Removal of the acetyl and isopropylidene groups followed by esterification furnished methyl arjunolate (III) the melting point of which is undepressed by an authentic sample, thus conclusively establishing that tomentosic acid is a hydroxyarjunolic acid (XII; R = H) with all its steric significance.
Evidence for the position of the fourth hydroxyl was principally secured from the reactions of the ketone (XIV) and the anhydrolactone (X). The ketone (XIV) and also the triacetylmethylketo tomentosate (XV) are unreactive towards ketonic reagents showing the sterically hindered character of the ketonic group. Also,. the ketone (XIV) does not give a benzylidene derivative’s indicating the absence of a methylene group a to the carbonyl. Isomerization of XV in the presence of alkali results in the
l7 D. H. R. Barton, D. I. J. Ives and B. R. Thomas, J. C/tern.Sot. 2056 (1955). ‘I D. H. R. Barton, A. J. Head and P. J. May, J. Chem. Sot. 935 (1957).
Chemistry of Terminalia
spies-VI
831
formation of an a,@msaturated ketone (XVI) (31[1=248 rnp, log E, 352). The 12(13) double bond, not originally conjugated to the carbonyl group, has moved to the 13( 18) positions forming an a&unsaturated ketone (XVI).‘O Ruzicka et ~1.‘~observed that the lPketo-methyl oleanolate (as XV) from methyl siaresinolate (VI; R, = OH; R = Me) undergoes similar isomerization with alkali. From this analogy, the fourth hydroxyl in tomentosic acid is probably in the 19th position. The facile dehydration to give the anhydrolactone diacetate (X) may be expected only with hydroxyls at positions 6, 11 and 19. Position 6 is eliminated since triacetylmethylketo tomentosate (XV) is not identical with methyl terminonate (XVII);13 tomentosic acid is not even an epimer of terminolic acid (II). Since the anhydrolactone triacetate (X) cannot be oxidized with Cr,O,-pyridine or even with Cr,O,-HOAc, it may be safely presumed that there is no a-methylene group to the double bond, thus eliminating the 1lth position and also the alternate structure (XVIII) for the anhydrolactone. The fourth hydroxyl can, therefore, only be in the 19th position which further relates tomentosic acid with the only known 1Phydroxytriterpene carboxylic acid, namely siaresinolic acid (VI; R = H; R, = OH), the chief constituent of Siamese gum benzoin.20 The lPhydroxy1 in tomentosic acid should be capable of dehydration as in siaresinolic acidzl to give methyldehydroarjunolate (XIX). No methyldehydro arjunolate could be obtained from triacetylmethyltomentosate (XII, R = Me) on reflexing with POCl,-pyridine, but dehydration did occur giving an isomeric compound which may be termed methylanhydrotomentosate. The latter contained an easily reducible double bond not conjugated with the 12( 13) double bond as determined from the U.V. absorption spectrum which has a single peak at 216 rnp. Attempts were next made to dehydrate methyl tomentosate with other reagents like P,O,-benzene and selenium dioxide .22 Under varying conditions the former reagent With selenium dioxide only resins were gives only methylanhydrotomentosate. obtained when refluxed for 10-20 hr in acetic acid medium, but as in every experiment metallic selenium was deposited in the first 10-15 minutes, if the reaction was terminated after 15 minutes, methyldehydroarjunolate (XIX) was secured in quantitative yield. The use of selenium dioxide as a dehydrating agent is reported in the literature only in the case of a triterpenoid, jaegosapogenol,a2 whose constitution is still unsettled. The mechanism of this dehydration is obscure but solvolysis of the selenous acid ester may take place. Similar dehydration was affected with the pcntol-tetraacetate (XX, R = AC), obtained by the lithium aluminium hydride reduction of methyl tomentosate (XII, R = Me). The dehydro derivative was found to be identical with tetraacetyldehydrobarringtogenol (XXI) which was obtained by selenium dioxide dehydrogenation of barringtogenol (tetraacetate). Thus tomentosic acid (XII R = H) behaves differently with POCl,-pyridine and with selenium dioxide giving rise to two isomeric anhydro compounds. The formation of dehydroarjunolate conclusively establishes the 19th position for the fourth hydroxyl. It is evident, that the steric configuration of the 19th hydroxyl must differ from that in I’ L. Ruzicka, A. Grob, R. Egli and 0. Jeger, Heh. Chin. Acta 26, 1218 (1943). *OP. Bilham, G. A. R. Kon and W. C. J. Ross, J. Chem. Sot. 540 (1942). *I D. H. R. Barton and N. J. Holness, J. Chem. SIC. 78 (1952). ** S. Tobinaga, Chem. Ahrr. 52, 13686 (1958).
L. RAMACHANDRARow and G. S. R. SUBBA RAO
832
siaresinolic acid in which the 19th hydroxyl is a-axial and being truns situated to 18(/3)H, it readily suffers dehydration. Obviously, therefore, in tomentosic acid, the
PcOH,d
4cOHc,d ’
~
XEI
xx
19th hydroxyl must have the epimeric @-equatorial configuration which alone can explain the formation of a new anhydrotomentosic acid with POCl,-pyridine. The course of dehydration with this reagent requires further study which is in progress. Tentatively, however, tomentosic acid may be expressed as 2a,3/3,19,!I,23-tetrahydroxyolean-12-ene-28-oic acid (XII, R = H). EXPERIMENTAL M.P,s are uncorrected. Optical rotations were measured in chloroform unless otherwise stated and the IN absorption spectra recorded in ethanol. The compounds described were all purified by chromatographic adsorption on alumina and before analysis, dried at 100”/0.2 mm for 6 hr. Exrruclion of the hearrwood
of Terminalia tomentosa
The powdered wood (2 kg) was extracted successively with pet ether (b.p. W), ether and acetone. Colourless crystalline solids separated out during extraction with ether and acetone necessitating their removal and pursuing the extraction with fresh solvent. Petrofeum ether exfrucl. The pale yellow extract, when concentrated to 200 ml deposited a light yellow solid (compound A m.p. 260-290” ; 0.75 g). From the filtrate, all the solvent was removed and the thick orange yellow oil slowly deposited a colourless solid (compound B; 0.5 g). Ether extract. During the extraction, a colourless crystalline compound (31.5 g) separated. It was removed by filtration and evaporation of the filtrate deposited an additional 22.0 g of the compound. The total solids (53.5 g) were refluxed with acetone (2 1.) and the undissolved material (m.p. 332-334”; 5 g) remobcd by filtration. Evaporation of the filtrate afforded a pale yellow mass which was dissolved in 4”/, methanolic KOH and extracted continuously with ether in a liquid-liquid extractor. The dried ether extract on evaporation yielded a small amount (I .2 g) of the neutral fraction (compound D; m.p. 260-280”). The alkaline layer was acidified with dil HCl (Congo red) and the precipitate after several crystallizations from anhydrous acetone yielded 21 g of a colourless solid (compound C, m.p. 320-324”). Acetone extract. The solid (compound E, 90 g) after 3 crystallizations from acetone yielded microprisms, m.p. 332-334”. The filtrate from compound E deposited impure brown solid. Compound
A
Oleunolic acid. Compound A is soluble in aq. Na,CO, and aq. NaOH and was purified through its potassium salt and crystallized from methanol as needles (0.1 g); m.p. 306309”; (&,‘“, +76” (c, 1.05). Lit0 m.p. 306308”. (Found: C, 78.7; H, 10.4; CSOHIBOSrequires: C, 78.9; H, 10.6%). Methyl oleunolure (diazomethane) crystallized from methanol as irregular plates, m.p. 200-202”, (&,“, -1-70”(c, 1.0). Lit.’ m.p. 204”. (Found: C, 78.82; H, 10.51; OMe, 6.3; C,,H,,O, requires: C, 79.15; H, 1064; OMe, 6.6%). Acetate (acetic anhydride-pyridine) crystallized from acetone-pet ether as colourless prisms, m.p. 260-261”. (Found: C, 77.02; H, 1@4; C,,H,,O, requires: C, 77.10; H, IO.1 %).
Chemistry of Termtitaiia species-VI
833
Compotmd B /?-sitosterol. Compound B, after two crystallizations from methanol separated as prismatic needles m.p. 136-137”. (a)“,‘” -35” (c, 1.5) Lit.’ m.p. 136137”, (ah, -35”. (Found: C, 83.78; H, 1240; C,,H,,O requires: C, 8404; H, 12.08%). /?-sitosterof acetate (acetic anhydride-pyridine) crystallized as needles from methanol m.p. 126 127”; (u)“d”. -38” (c, 2.2). Lit.*m.p. 126127”; (a)n - 35”. (Found: C, 81.3; H, 10.8; C,,H,,O, requires: C, 81.5; H, 11.5%). Compound C Tomentosic acid (XII, R 7 H). Compound C was dissolved in 2N methanolic KOH and the sparingly soluble potassium salt continuously extracted with ether. After decomposition with dil HCI (Congo red), the product was crystallized from acetone as micro prisms m.p. 328-330” (a):“, +64” (c, 0.32 in ethanol). A sample (100 mg) of the acid in acetone (30 ml) was eluted from a column of silica gel (8 g) with benzene-methanol (1: 1; 200 ml) and after evaporation of solvent, the residue crystallized from anhydrous methanol as colourless prisms, m.p. 328-330’. (Found: C, 71.8; 71.7; H, 9.3, 9.6; C,,H,*O, requires: C, 71.4 and H, 9.5%). The acid is readily soluble in acetic acid, pyridine and sparingly soluble in organic solvents. In cone H,SO, it changes from colourless to orange pink, and exhibits a pale yellow colour with tetranitromethane. Methyl tomentosate (XII, R = Me). Tomentosic acid (I g) in methanol (20 ml) was treated with ethereal diazomethane. Next day, the ether was removed and the residue crystallized from methanol as colourless prisms m.p. 218-220”. A solution of the methyl ester (100 mg) in dry benzene (20 ml) was chromarographed on alumina. It was eluted with ether-methanol (3: 1). Evaporation of the solvent and two crystallizations from methanol gave the methyl ester as colourless needles; m.p. 221-222”; (a)r, +72” (c, 0.53). (Found: C, 71.4; H, 9.6; OMe, 6.3; C,,H,,O, requires: C, 71.8, H, 9.6 and OMe, 6.2%). AcetyIation of tomentosic acid Tomentosic acid (1 g) in acetic anhydride (5 ml) and dry pyridine (5 ml) was allowed to stand I2 hr and then diluted with water. The triacetate (0.85 g) after crystallization from methanol and acetone yielded an amorphous powder with a m.p. of 168-186”. Chromatographic purification over alumina did not improve the crystalline nature, nor the m.p. (Found: C, 68.8, H, 8.65 OAc, 18.2 C,,H,,O, requires: C, 68.6; H, 8.57; 3-OAc 20.46%). Tomentosic acid (I g) was suspended in acetic anhydride (5 ml) and a drop of perchloric acid added. There was an immediate rise in temp and discoloration of the solution. This was poured into water and the tetraacetate crystallized as above as an amorphous powder. (Found: C. 67.5; H, 8.5; OAc, 22.9, C,,H,,O,, requires: C, 67.86; H, 8.33; 4-OAc, 25.5%). Tomentosic bromolactone (VII, R = OH) To a mixture of tomentosic acid and sodium acetate (0.5 g) dissolved in 10 ml acetic acid, a solution of bromine in acetic acid (4%. 10 ml) was added drop by drop while shaking. After 1 hr, the reaction mixture was poured into water (50 ml) containing sodium thiosulphate and the bromolactone which separated crystallized from methanol as colourless needles, m.p. 234-236”; (a):“, $-45” (c. 1.48) (Found: C, 61.5; H, 8.8; C,,H,,O,Br requires: C, 61.7 and H, 8.1 %). Methy/ 12,13-epoxy-tomentosate (VIII, R = OH) Methyl tomentosate (500 mg) in ether-dioxan (3: I, 40 ml) was treated with ethereal monoperphthalic acid (6 ml; 0.57N) and kept at 0” for 17 days. The mixture was then washed with N/4 NaOH and dried over potassium carbonate. Removal of the solvent furnished a colourless residue which after two crystallizations from methanol gave methyl 12,13epoxy tomentosate as colourless cubes (320 mg) m.p. 158-160”; (a)g”, t-18” (c. 1.5) (Found: C, 69.2; H. 9.5; C,,H,,O, requires: C, 69.6; H, 9.4%). Methyldihydro-12-oxo tomentosate (IX, R = OH) (a) A solution of the epoxide (0.75 g) in acetic acid and a trace of 10% HCI was heated on a
834
L. RAMACHANDRARow and G. S. R. SUBBA RAO
steam bath for 8 hr, diluted with water and the product which could not be crystallized was subjected to hydrolysis with 4% methanolic KOH. The methyl dihydro-12-oxo tomentosate crystallized from methanol in needles (0.25 g); m.p. 196-197”: (a)z”, -32” (c, 1.25) (Found: C, 69.92; H, 9.5, C,,H,,O, requires: C, 69.6 and H, 9.4%). (b) A solution of methyl tomentosate tetraacetate in acetic acid and 30 % H,O, (1 ml) was heated on a water bath at 100” for 8 hr. The reaction mixture was poured into water and extracted with ether. Evaporation of the dried ether extract afforded a gum which was deacetylated by refluxing with 50 ml 4% methanolic KOH for 1 hr. The dihydro-oxo-ester (0.25 g) was crystallized from methanol as small prisms, m.p. 196197”, undepressed with the sample obtained above. Hydrolysis of tomentosic bromolactone Methyldihydro-12-oxo-tomentosate (IX, R = OH). Tomentosic bromolactone (1 g) was refluxed with 3 ‘A KOH for 1 hr. It was poured into water and as the precipitate failed to crystallize. it was isomer&d by dissolving in chloroform and saturating with dry HCI at room temp. Removal of the solvent and crystallization from methanol gave methyl dihydro-12-oxo tomentosate, m.p. 192-196”; (a)=, -30” (c, 1.6) undepressed by the sample obtained above. (Found: C, 69.5; H, 9.8; CtlHIDO, requires: C, 69.6 and H, 9.4%). Anhyako tomentosic lactone diacetate Tomentosic acid (5 g) was dissolved in 50% HRr-HOAc and after 48 hr at room temp, the purplish red solution was diluted with water. The precipitated anhydro tomentosic lactone diacetate crystallized from methanol in needles, m.p. 233-235”; (a$“, -20” (c, 15). The W absorption gave IBfb6”01210 m&log E, 3.12) and 220 mu (log E 2.53). The IR spectrum showed characteristic bands a7.Y,mr 2.97 p (3368 cm-r for OH), 5.67 y. 5.76 p (1764 cm-l, 1736 cm-l) for lactone, 1 l-63 p (860 cm-l) and 12.02 ~c (834cm-r) for a trisubstituted double bond (Found: C, 71.6, H, 8.5, OAc, 11.4; C,,H,,O, requires: C, 71.6, H, 8.6 and 2-OAc, 15X@%). The lactone diacetate gave no colour with tetranitromethane. Anhydrotomentosic lactone (X) Anhydrotomentosic lactone diacetate (1.2 g) was refluxed with 4% methanolic KOH. After 4 hr it was poured into water and continuously extracted with ether. The dried ether extract, on removal of the solvent, gave a pale yellow mass which crystalked from acetone in small prisms (0.85 g); m.p. 340-342”, (a~):~, -9” (c, O-4) (Found: C, 73.68; H, 9.87; CloHIIOI requires: C, 74.0 and H, 9.5 %). The compound gave no colour with tetranitromethane and has the UV absorption at cz 210 rnp (log E. 3.12) and 220 rnp (log e, 2.50). Anhydrotomentosic lactone triacetate Anhydrotomentosic lactone or its diacetate was acetylated with acetic anhydride and a trace of perchloric acid. The M-acetate crystallized from methanol as colourless plates, m.p. 250-252”; (a)tW, +1*8” (c, 1.5) (Found: C, 69.98; H, 8.97, CIIH5,0s requires: C, 70.55 and H, 8*55”%). O,@isopropylidkne-anhydrotomentosic lactone Anhydrotomentosic lactone (500 mg) in 25 ml dry acetone was treated with a drop cone HCI. The lactone dissolved and deposited the isopropylidene derivative which crystallized from aqueous acetone (450 mg) as colourless transparent prisms; m.p. 319-320”. (a)r, + 8” (c, 0.52) (Found: C, 74.8; H, 9.8; C,,H,,O, requires: C, 75.2 and H, 9.6%). Anhyaio-epoxy-tomentoosic lactone triacetate Anhydrotomentosic lactone triacetate (1.0 g) in acetic acid (20 ml) was treated with 30 % hydrogen peroxide (1 ml) and the mixture heated at 100” for 3 hr. The product was isolated by dilution with water followed by crystallization from methanol giving the anhydro-epoxy-tomentosic lactone - 18” (c, 0.96) (Found : C. 68.5 ; H, triacetate as colourless plates (600 mg) m.p. 270-272”; (ar 8.45; C,,H,,O, requires: C, 68.8 and H, 8.28 “/,).
Chemistry of Terminalia species-VI
835
O,O+opropyli&ne methyl tomentosate Methyl tomentosate (100 mg) was suspended in dry acetone (10 ml) and treated with a drop of cont. HCI. After 12 hr at o”, the solution was poured into dil ammonium hydroxide solution and extracted with ether. The dried ether extract on evaporation gave a semisolid which crystallized from +68” (c, 1.2) (Found: C, 735; H, 9.9; CIIHI,OI acetone in prisms (70 mg) m.p. 168-170”; (a)r, requires: C, 73.1 and H, 9.7%). Pyrolytic experiments A mixture of tomentosic acid (1 g) and finely divided copper (5 g) was heated to 270-290” for 1 hr, while passing a stream of carbon dioxide. The evolved gases were passed into a saturated solution of dimedone. The precipitate (20 mg) was collected and crystallized from alcohol as colourless needles, m.p. 186-189”. undepressed by an authentic formaldehyde dimedone derivative. Similar experiments with methyl tomentosate and anhydrotomentosic lactone also gave formaldehyde. Oxidation with soa%m metaperiodate (a) Methyl tomentosate. An ethanolic solution of methyl tomentosate (200 mg) was treated with aqueous sodium metaperio-date (10 ml; O*lN), the vol made up to 50 ml with ethanol and the solution kept in the dark at room temp. Aliquot portions (10 ml each) were removed after &2), 4 and 24 hr. The excess of periodate was estimated using standard sodium arsenite solution. The compound absorbed 0.41,0.82.0.87 and 099 moles of periodate respect,ively showing the presence of a,&glycol system in the molecule. (b) O,O-isopropylidenemethyl tomentosate. Isopropylidenemethyl tomentosate (100 mg) was treated with excess of sodium metaperiodate and quantitative estimations as before, showed no oxidation. The compound was recovered unchanged after 24 hr. (c) Anhydrotomentosic lactone. Anhydrotomentosic la&one (100 mg) was treated with excess of sodium metaperiodate (8 ml; O.lN). The estimation was carried out as before and the oxidation corresponded to 36, 80, 88 and 99 % of 1,Zglycol unit. (d) O,O-Isoprypylidene-anhydrotomentosic lactone. Isopropylidene-anhydrotomentosic lactone (100 mg) did not react with aqueous sodium metaperiodate. Oxidation of methyl tomentosate with lead tetraacetate Methyl tomentosate (100 mg) was dissolved in A.R. acetic acid (20 ml) and was treated with 15.2 times the molar excess of lead tetraacetate. Periodically in 10 ml samples the excess lead tetraacetate was estimated iodometrically. The rate constants for the oxidiaton were calculated according to the method of Cordner and Pausacker.= The oxidation of methyl tomentosate was completed in 14 hr and the rate constant was found to be K = 1.3 x 10-l lit. mol-’ se& thus corresponding to an a,&glycol system in the molecule. 2-Acetyl-3,23-isopropyIidenemethyl tomentosate (XIII) 3,23-Isopropylidenemethyl tomentosate was acetylated with acetic anhydride and pyridiie. The acetate failed to crystallize from methanol and separated as amorphous powder. (Found: C, 71.8; H, 9.8; C,,H,,O, requires: C, 72.0 and H, 9.4%). 2-Acetyl-3,23-isopropylidene-19-keto-methyl
tomentosate (XIV)
The above acetate (1.0 g) in dry pyridine (20 ml) was added to pyridinechromic anhydride (10 ml containing 05 g Cr,OS) at room temp. The orange Cr,O,) complex rapidly disappeared with precipitation of a dark brown product. After 2 hr, it was filtered off, washed with pyridine and the filtrate poured into water (200 ml). This was extracted with ether and evaporation of the dried ether extract resulted in a gum which was purified (alumina) and recrystallized from methanol as needles, m.p. 204-205”; (a),““, +20” (c, 1.2) (Found: C, 71.9; H, 9.4; C,H,,O, requires: C, 72.25 H, 9-03”/,). 3,23-lsopropyliabe-19-keto-methyl
tomentosate
3,23Isopropylidenemethyl tomentosate (1 .Og) was similarly oxidized with pyridine and chromic acid at room temp yielding 3,23_isopropylidene 19-keto-methyl tomentosate as stout needles (0.7 g) *8 J. P. Cordner and K. H. Pausacker, J. Chem. Sot. 102 (1953).
836 m.p. 228-230”. (z)r, H, 9.35 “/,).
L RAMACHANDRARow and G. S. R. + 38’ (c. 1.04) (Found:
SUBBA RAO
C, 72.5; H, 9.25; C,,H,,O,
requires:
C, 73.38 and
Merhyl-19-keto-tomentosare Similar oxidation of methyl tomentosate with excess of chromium trioxide and pyridine (4 moles) gave methyl-19-keto tomentosate which crystallized from methanol as prisms (120 mg) m.p. 269-270”; (IL%‘, i-40” (c, 1.2) (Found: C, 72.8; H, 9.4: C,,H,,O, requires: C, 72.88 and H, 9.3%). Reduction of 2-acetyl-3,23-isopropylidene-19-kero-merhyl tomer.tosate to methyl arjunokate (III) Sodium (0.2 g) in diethylene glycol(l0 ml) was heated to 180”. anhydrous hydrazine (4 ml) added and the mixture refluxed at 180”. 2-Acetyl-3,23-isopropylidene 19-keto-methyl tomentosate (I g) in ethylene glycol was added quickly and the solution refluxed for 12 hr. The temperature was then raised to 210” and the solution refluxed at this temp for 24 hr. The reaction mixture was then poured into water and the precipitate collected. Removal of the isopropylidene and acetyl groups and esterilication with ethereal diazomethane afforded a gum which was purified by chromatography on alumina. Elution with ether-methanol (3: 1) and crystallization from methanol deposited the methyl arjunolate (100 mg) as needles, m.p. 205-207”; (a)r, $67” (c. 0.5) undepressed by an authentic sample of methyl arjunolate. (Found: C, 73.82; H, 9.81; C,,H,,O, requires: C, 74.10 and H, 9.96%). The modified Wolff-Kishner reduction with both 3,23-isopropylidene-19-keto methyl tomentosate and triacetylmethyl-19-keto tomentosate also afforded methyl arjunolate (Ill). Selenium dioxide oxidation of methyl tomentosale tetraacetate A solution of tetraacetylmethyl tomentosate (0.8 g) in A.R. acetic acid (50 ml) containing resublimed selenium dioxide (0.4 g) was heated under reflux for 17 hr. After removal of metallic selenium, the solvent was evaporated under red press. The brown residue was dissolved in ether, washed with sodium bicarbonate and dried. Removal of the solvent afforded a glassy mass which failed to crystallize but showed the characteristic UV absorption iEtxu, 243 m,u (log E, 4.21). 251 rnp (log E, 4.31) and 260 m/d (log E, 4.10). Hydrolysis of the above residue with 20% methanolic potash did not afford any crystalline material.
Triacetyl methyl-19-kero tomenfosate (xv) Triacetylmethyl tomentosate (1 g) in pyridine (6 ml) was added to Cr,O,-pyridine complex (10 ml, containing 0.5 g Cr,O,) at room temp. After 1 hr the brown precipitate was filtered off and the filtrate diluted with water. The precipitate was collected and separated from acetonepet ether as an amorphous powder (0.6 g) which has the UV absorption ct: 292 rnp (log E, 1.92). (Found: C, 68.5; H, 8.6; C,,H,,O, requires: C, 69.16 and H, 8.41%). Methyl 2,3,23-trihydroxy-olean-13-en-28-oate (XVI) Triacetyl-lPketo-tomentosate (0.4 g) was refluxed with 2N methanolic KOH for 4 hr. The reaction mixture was poured into water, extracted with ether and the dried ether extract on evaporation gave a glassy residue. This crystallized from acetone in small prisms (0.2 g) m.p. 238-240 (ak”, -13” (c, 1.09). The compound has the UV absorption A”,:9” 248 rnp (log E, 3.52) (Found: C, 72.3; H, 9.45; C,,H,,O, requires: C, 72.1 and H, 9.3%). Methyldehydro arjunolate (XIX) Triacetylmethyl tomentosate (800 mg) in A.R. acetic acid (20 ml) containing a little acetic anhydride (1 ml) was heated to boiling with selenium dioxide (100 mg). After 10 min and removal of metallic selenium the filtrate was diluted with water and hydrolysed with 2N methanolic alkali. The methyldehydro arjunolate crystalltid as colourless needles from methanol (180 mg) m.p. 250-251”; (a)‘,““, - 150” (c, 1.25) undepressed by admixture with an authentic sample. It has the triple U.V. C, 74.3; H, 9.9, C,,H,,O, absorption A,,, 243, 252, 261 rnp (log c, 4.33, 4.38, 4.19) (Found: requires: C, 74.4 and H, 9.6 %).
Chemistry of Terminaliu species--VI Reduction
of methyl
837
with LiAlH,
tomentosate
To a suspension of LiAIHI (1 g) in dry ether (200 ml) in an atmosphere of nitrogen, an ethereal solution of methyl tomentosate (1.0 g; 50 ml) was added dropwise. The mixture was stirred for 2 hr, left overnight and then decomposed by addition of ice cold dil H$O, and extracted with ether. The dried ether extract, on evaporation gave a glassy residue. The pentahydroxy-carbinol (XX) crystallized from methanol in prisms (200 mg) m.p. 280-282”, (a)‘,““, +50” (c, 1.5 in ethanol) (Found: C, 73,57, H, 10.5; C,&,O, requires: C, 73.46 and H, 10.2%). Terraacetate (XX). The tetraacetate (A@-pyridine) of the penrahydroxy compound crystallized from methanol in long needles m.p. 265-266”; (a):“, -I 42 (c, @3). Dehydrobarringtogenol
tetraacetate
(XXI)
The above tetraacetate (70 mg) in A.R. acetic acid was refluxed as before with selenium dioxide (40 mg). The dehydro compound was purified (alumina) and crystallized from methanol in needles m.p. 196-197”; (a):’ -72” (c, 0.8) unchanged by an authentic sample of dehydrobarringtogenol tetraacetate.* (Found: C, 71.5; H, 8.9; Ca,,H,,Os requires: C, 71.2 and H, 8.8%). Examination
of compound
D
(IV). The neutral fraction from the ether extract crystallized from acetone as microprisms m.p. 289-290” ; (a) p, f22” (c, 0.8 in ethanol). This was undepressed by a sample obtained by LiAIHI reduction of methyl arjunolate. (Found: C, 75.8; H, 10.5; C,,H,,O, requires: C, 75.95 and H, 10.55 %). The compound gave a cherry red solution in sulphuric acid; Liebermann-Burchard’s reaction, pink rapidly changing to violet with strong fluorescence. Anantaraman et al. recorded for barringtogenol, m.p. 290-291”; (ah,, +18”. Burriqtogenol
Reduction
of methyI arjunolate
with LiAIHS
Barringtogenol (IV). To a suspension of LiAIHl (200 mg) in dry ether (200 ml) was added dropwise, while stirring in an atmosphere of nitrogen, an ethereal solution of methyl arjunolate (200 mg) and the mixture left overnight. After 24 hr, ice-cold water (200 ml) containing a little H,SO, was slowly added and the ether layer separated and dried. Removal of the solvent afforded a colourless gum which was crystallized from acetone, yielding barringtogenol as micro prisms (110 mg) m.p. 290-291”; (a):“, j-20” (c, 1.8 in ethanol) (Found: C, 75.63; H, 10.8; C,,H,,O, requires: C, 75.95 and H, 10.55%). Acetate. (Acetic anhydride-pyridine) crystallized from methanol as small needles m.p. 268-270”; (Found: C, 70.85; H, 9.5; (a) 2,” + 18” (c. 1.2) undepressed by barringtogenol tetraacetate. C,,H,,O, requires: C, 71.0 and H, 9.0%). Examination
of compound
E
Compound E crystallized from a large volume of acetone as shining microprisms, m.p. 332-336” (a):“, +63” (c, 0.51 in ethanol) (Found: C, 73.67, H, 9.47; C,,H,,O, requires: C, 73.77 and H, 9.9%). The compound dissolves in cone H,SO, to give a yellow solution changing to red; LibermannBurchard’s reaction pink changing to reddish brown and developed a faint yellow colour with tetranitromethane. King et a1.O record for arjunolic acid m.p. 337-240”; (ah,, $63.5”. Methyl arjunolafe (III). Compound E was methylated with excess of ethereal diazomethane. The methyl ester crystallized from methanol as colourless needles m.p. 209-211”; (a)r, +68” (c, 2.2) (Found: C, 73.8; C, H, 10.2, C,,H,,O, requires: C, 741 and H, 10.0%). Arjunolic
acid (I).
Arjunolic bromolactone
A solution of the compound E (100 mg) and sodium acetate (200 mg) in acetic acid (4 ml; 90%) was stirred during dropwise adddition of 4 ‘A bromine in acetic acid (5 ml). After 1 hr, the mixture was poured into water containing sodium thiosulphate, the precipitate collected and crystallized from methanol. The bromolactone separated as colourless needles (120 mg) m.p. 24W, (a)$“, +53” (c, 1.2). (Found: C, 63.4, H, 8.1; C,,H,,O, Br requires: C, 63.5 and H, 8.3%); Lit.’ m.p. 240-244’.
838
L.
RAMAC?iANDRA
Row and G. S. R.
SIJLIBARAO
Ackrwwfe&ements-Our thanks are due to Prof. F. E. King, F.R.S., and J. W. W. Morgan for kindly confirming our identification of arjunolic acid, to the Director, National Physical Laboratory, New Delhi, for the I.R. Spectra and to Prof. T. R. Seshadri, F.R.S., for the UV absorption spectral data. One of us (G. S. R.) wishes to express his grateful thanks to the Council of !kientific & Industrial Research, New Delhi, for a fellowship.