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An A-ring contracted triterpenoid from Hyptis suaveolens
Phytochemistry. Vol. 29, No. 4, pp. 1326- 1329. 1990.
003 1 9422190 $3.00 + 0.00
Printed in Great Britain.
AN A-RING CONTRACTED K. V. Department
19 1990 Pergamon Press plc
TRITERPENOID
RAJA RAO, L. J. M.
of Chemistry,
Key Word Index-Hyp;ptis suaveohs;
RAO and N. S.
Nagarjuna
University,
(Receired
4 September
Labiatae;
FROM HYPTZS SUA VEOLENS
hyptadienic
PRAKASA
Nagarjuna
RAO*
Nagar 522 510. India
1989)
acid: A( I)-1.19~dihydroxy-urs-2(3).12-dien-28-oic
acid; triterpene.
Abstract-From the aerial parts of Hyptis suaveolens, a novel triterpenoid, hyptadienic acid, was isolated and its structure elucidated as A(1)-1,19~-dihydroxy-urs-2(3),12-dien-28-oic acid. This is the first report of a naturally occurring A-ring contracted triterpene outside the lupane series.
INTRODUCTION
Recent investigation of Hyptis species led to the isolation of cytotoxic principles [l] and prompted us to reinvestigate the widely used indigenous drug Hyptis suaveolens Poit. [2-51 for active principles. We report the structural elucidation of a novel A-ring contracted triterpene, hyptadienic acid (l), present in the aerial parts of H. suaveolens. A-ring contracted triterpenes are rare. So far only nine such compounds are reported from natural sources. All these nine compounds are lupane derivatives and were isolated from Rhamnaceae [6-131 and Alangiaceae [14-161. This is the first report of a naturally occurring A-ring contracted ursene.
RESUI,TS AND DISCUSSION
Hyptadienic acid (1) (C,,H,,O,, [Ml,’ m/z 470) gave an intense violet colour in the Liebermann-Burchard reaction for a triterpenoid. Its IR spectrum showed absorption bands at 3500-3200, 1710, 1630 and 830 cm-’ indicating the presence of hydroxyl and carbonyl groups and a trisubstituted double bond. Two other absorption
bands at 1010 and 920cm-’ suggested the presence of primary and tertiary hydroxyl groups [17]. Its conversion to a monomethyl ester (2) [C3,H4804, [M]’ m/z 484, IR vi:: 1730 cm-‘, ‘HNMR 63.60 (3H, s)] upon treatment with diazomethane suggested the presence of a carboxylic group in 1. Both 1 and 2 formed monoacetates 3 [C32H4805r [Ml+ m;‘z 512, ‘HNMR 62.09 3H, s) and 4 [C,,H,,O,, [M]’ m’-_ 526, ‘H NMR (52.10 (3H, s)] respectively, indicating the presence of a hydroxyl group. Further, the IR spectra of 3 and 4 showed absorption bands at 3420 and 920 cm -’ assignable to a free tertiary hydroxyl group [ 171. The signals at (55.34 (IH) and 5.40 (1H) in the ‘HNMR spectra of 2, 3 and 4 and b 128.3 (d), 134.0 (d), 140.2 (s) and 156.7 (s) in the ‘“CNMR spectrum of I (pyridine-d,) suggested two trisubstituted double bonds. The irradiation experiments and UV spectrum of 1 suggested two isolated double bonds. The mass spectral fragmentation pattern of 1 (PI;- 264, 246, 219, 218, 201 and 146) [18. 193 and the presence of six tertiary methyl and one secondary methyl signals in the ‘H NMR spectra 2-4 (Table 1) suggested the partial structure S for hyptadienic acid. The signals at ,i 128.3 (d),
Table
1 Methyls
CH,OR*
H-3
H-12
H-18
23
24
25
26
27
29
30f
Others
4.25
5.40
5.34
2.50
0.94
1.03
1.12
0.72
1.27
1.20
0.95
3.60 (COOMe)
Hyptadienic acid acetate (3)
4.60
5.40
5.34
2.50
0.94
1.07
1.14
0.78
1.27
1.21
0.95
2.09 (OCOMe)
Acetyl methyl hyptadienate
4.60
5.40
5.34
2.50
0.94
1.03
1.13
0.76
1.27
1.20
0.95
Methyl
hypta
dienate
(2)
(4)
3.60
(CO,Me) 2.10 (OCOMe) *q,J=llHz. td. J = 6.7 Hz 1326
Short Reports Table C 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
6 [20] 38.4 68.3 78.4 38.1 49.6 17.9 32.4 40.1 47.0 38.1 23.4 129.2 138.2 41.0 28.1 26.0 47.7 52.8 73.2 41.2 25.2 37.7 27.7 21.5 16.1 17.0 24.6 184.5 27.6 16.1
-
1 PO1
2
8 [21]
1
12 [25]
-
44.1 70.2 80.2 39.5 55.0 18.4 32.7 40.2 47.3 38.3 23.8 129.0 138.3 41.4 28.5 26.1 47.9 53.2 73.2 41.3 25.5 37.5 28.3 17.7 16.4 17.0 24.4 182.2 27.4 16.1
50.3 69.6 84.7 38.8 57.4 68.8 41.8 41.2 49.1 40.3 24.7 129.6 139.4 42.1 29.5 27.8 49.7 55.1 73.6 43.1 26.6 39.0 29.0 16.6 18.5 18.8 24.8 182.2 27.1 18.5
60.8 156.7 134.0 42.1 63.7 17.7 34.7 42.1 42.4 51.0 26.9 128.3 140.2 42.3 29.7 27.0 48.3 54.8 72.8 43.7 26.4 38.4 30.1 21.7 18.9 16.6 25.3 180.5 27.2 16.6
t s d s d c c s d s c d s s c c s d s d c c 4 4 q q q s q q
40.7 38.9 37.8 61.6 18.8 34.7 41.4 50.0, 45.6 23.6 25.1 38.3 43.0 27.8 35.7 42.9 48.4 48.0 150.7 29.9 40.1 32.7 26.2 16.1 16.3 14.7 18.0 109.2 19.4
REFERENCES
1. Yamagishi, T., Zhang, D. C., Chang, J.-J., McPhail, D. R., McPhail, A. T. and Lee, K. H. (1988) Phycochemistry 27, 3213. 2. Chopra, R. N., Nayar, S. N. and Chopra, I. C. (1956) Gfossary ofIndian Medicinal Plants, p. 139. CUR, New Delhi.
1329
3. The Wealth of India (1959) Raw Materials V, p. 159. CSIR, New Delhi. 4. Chaudhury, R. R. and Haq, M. (1980) Bull. Med. Echnohoc. Res. I, 408. 5. Saluia, A. K. and Santani, D. D. (1981) Indian Drugs 19. 127. 6 Julian, P. K., Pikl, J. and Dawsbn, R. (1938) J. Am. Chem. sot. 60, 77. 7 Mayo, P. de and Starrat, A. N. (1962) Can. J. Chem. 40,788. 8. Mayo, P. de and Starrat, A. N. (1962) Can. J. Chem. 40, 1632. 9. Guise, G. B., Ritchie, E. and Taylor, W. C. (1962) Aust. J. Chem. 15, 314. IO. Eade, R. A., Ellis, J., Harper, P. and Simes, J. J. H. (1969) J. Chem. Commun. 579. 11. Branch, G. B., Burgess, D. V., Dunstan, P. J., Foo, L. Y., Green, G. H., Mack, J. P. G., Ritchie, E. and Taylor, W. C. (1972) Aust. J. Chem. 25, 2209. 12. Roitman, J. N. and Jurd, L. (1978) Phytochemistry 17, 491. 13. Baxter, R. L. and Walkinshaw, D. M. (1988) Phytochemistry 27, 2350. 14. Eade, R. A., Ellis, J., and Simes, J. J. H. (1967) Aust. J. Chem. 20, 2737. 15. Burbage, M. B., Jewers, K., Eade, R. A., Harper, P. and Simes, J. J. H. (1970) J. Gem. Commun. 814. 16. Burbage, M. B., Jewers, K., Eade, R. A., Harper, P. and Simes, J. J. H. (1971) J. Chem. Commun. 195. 17. Takahashi, K. and Takani, M. (1978) Chem Pharm. Bull. 26, 2689. 18. Budzikeiwiez, M., Wilson, J. M. and Djerassi, C. (1963) J. Am. Chem. Sot. 85, 3688. 19. Potier, P., Das, B. C., Bui, A.-M., Janot, M.-M., Pourrat, A. and Pourrat, H. (1966) Bull. Sot. Chim. Fr. 3458. 20. Raja Rao, K. V., Rao, L. J. M. and Prakasa Rao, N. S. (1989) Planta Med. (in press). 21. Gopalsamy, N., Vargas, D., Gneno, J., Ricand, C. and Hostettmann, K. (1988) Phytochemistry 27, 3593. 22. Goh, E. M., Williams, A. H. and Holland, P. T. (1978) J. Chem. Sot. Perkin Trans I 1560. 23. Mayo, P. de., and Starratt, A. N. (1961) Tetrahedron Letters 259. 24. Sims, J. J. and Petters Jr, J. A. (1976) Phytochemistry 15, 1096. 25. Wenkert, E., Baddeley, G. V., Burtitt, I. R. and Moreno, L. N. (1978) Org. Magn. Reson. 11, 337. 26. Halshall, T. G. and Aplin, R. T. (1964) in Progress in the Chemistry of Organic Natural Products (Zechmeister, R.L., ed.), Vol. 22, p. 153. Springer, New York.
003 1 9422190 $3.00 + 0.00
Printed in Great Britain.
AN A-RING CONTRACTED K. V. Department
19 1990 Pergamon Press plc
TRITERPENOID
RAJA RAO, L. J. M.
of Chemistry,
Key Word Index-Hyp;ptis suaveohs;
RAO and N. S.
Nagarjuna
University,
(Receired
4 September
Labiatae;
FROM HYPTZS SUA VEOLENS
hyptadienic
PRAKASA
Nagarjuna
RAO*
Nagar 522 510. India
1989)
acid: A( I)-1.19~dihydroxy-urs-2(3).12-dien-28-oic
acid; triterpene.
Abstract-From the aerial parts of Hyptis suaveolens, a novel triterpenoid, hyptadienic acid, was isolated and its structure elucidated as A(1)-1,19~-dihydroxy-urs-2(3),12-dien-28-oic acid. This is the first report of a naturally occurring A-ring contracted triterpene outside the lupane series.
INTRODUCTION
Recent investigation of Hyptis species led to the isolation of cytotoxic principles [l] and prompted us to reinvestigate the widely used indigenous drug Hyptis suaveolens Poit. [2-51 for active principles. We report the structural elucidation of a novel A-ring contracted triterpene, hyptadienic acid (l), present in the aerial parts of H. suaveolens. A-ring contracted triterpenes are rare. So far only nine such compounds are reported from natural sources. All these nine compounds are lupane derivatives and were isolated from Rhamnaceae [6-131 and Alangiaceae [14-161. This is the first report of a naturally occurring A-ring contracted ursene.
RESUI,TS AND DISCUSSION
Hyptadienic acid (1) (C,,H,,O,, [Ml,’ m/z 470) gave an intense violet colour in the Liebermann-Burchard reaction for a triterpenoid. Its IR spectrum showed absorption bands at 3500-3200, 1710, 1630 and 830 cm-’ indicating the presence of hydroxyl and carbonyl groups and a trisubstituted double bond. Two other absorption
bands at 1010 and 920cm-’ suggested the presence of primary and tertiary hydroxyl groups [17]. Its conversion to a monomethyl ester (2) [C3,H4804, [M]’ m/z 484, IR vi:: 1730 cm-‘, ‘HNMR 63.60 (3H, s)] upon treatment with diazomethane suggested the presence of a carboxylic group in 1. Both 1 and 2 formed monoacetates 3 [C32H4805r [Ml+ m;‘z 512, ‘HNMR 62.09 3H, s) and 4 [C,,H,,O,, [M]’ m’-_ 526, ‘H NMR (52.10 (3H, s)] respectively, indicating the presence of a hydroxyl group. Further, the IR spectra of 3 and 4 showed absorption bands at 3420 and 920 cm -’ assignable to a free tertiary hydroxyl group [ 171. The signals at (55.34 (IH) and 5.40 (1H) in the ‘HNMR spectra of 2, 3 and 4 and b 128.3 (d), 134.0 (d), 140.2 (s) and 156.7 (s) in the ‘“CNMR spectrum of I (pyridine-d,) suggested two trisubstituted double bonds. The irradiation experiments and UV spectrum of 1 suggested two isolated double bonds. The mass spectral fragmentation pattern of 1 (PI;- 264, 246, 219, 218, 201 and 146) [18. 193 and the presence of six tertiary methyl and one secondary methyl signals in the ‘H NMR spectra 2-4 (Table 1) suggested the partial structure S for hyptadienic acid. The signals at ,i 128.3 (d),
Table
1 Methyls
CH,OR*
H-3
H-12
H-18
23
24
25
26
27
29
30f
Others
4.25
5.40
5.34
2.50
0.94
1.03
1.12
0.72
1.27
1.20
0.95
3.60 (COOMe)
Hyptadienic acid acetate (3)
4.60
5.40
5.34
2.50
0.94
1.07
1.14
0.78
1.27
1.21
0.95
2.09 (OCOMe)
Acetyl methyl hyptadienate
4.60
5.40
5.34
2.50
0.94
1.03
1.13
0.76
1.27
1.20
0.95
Methyl
hypta
dienate
(2)
(4)
3.60
(CO,Me) 2.10 (OCOMe) *q,J=llHz. td. J = 6.7 Hz 1326
Short Reports Table C 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
6 [20] 38.4 68.3 78.4 38.1 49.6 17.9 32.4 40.1 47.0 38.1 23.4 129.2 138.2 41.0 28.1 26.0 47.7 52.8 73.2 41.2 25.2 37.7 27.7 21.5 16.1 17.0 24.6 184.5 27.6 16.1
-
1 PO1
2
8 [21]
1
12 [25]
-
44.1 70.2 80.2 39.5 55.0 18.4 32.7 40.2 47.3 38.3 23.8 129.0 138.3 41.4 28.5 26.1 47.9 53.2 73.2 41.3 25.5 37.5 28.3 17.7 16.4 17.0 24.4 182.2 27.4 16.1
50.3 69.6 84.7 38.8 57.4 68.8 41.8 41.2 49.1 40.3 24.7 129.6 139.4 42.1 29.5 27.8 49.7 55.1 73.6 43.1 26.6 39.0 29.0 16.6 18.5 18.8 24.8 182.2 27.1 18.5
60.8 156.7 134.0 42.1 63.7 17.7 34.7 42.1 42.4 51.0 26.9 128.3 140.2 42.3 29.7 27.0 48.3 54.8 72.8 43.7 26.4 38.4 30.1 21.7 18.9 16.6 25.3 180.5 27.2 16.6
t s d s d c c s d s c d s s c c s d s d c c 4 4 q q q s q q
40.7 38.9 37.8 61.6 18.8 34.7 41.4 50.0, 45.6 23.6 25.1 38.3 43.0 27.8 35.7 42.9 48.4 48.0 150.7 29.9 40.1 32.7 26.2 16.1 16.3 14.7 18.0 109.2 19.4
REFERENCES
1. Yamagishi, T., Zhang, D. C., Chang, J.-J., McPhail, D. R., McPhail, A. T. and Lee, K. H. (1988) Phycochemistry 27, 3213. 2. Chopra, R. N., Nayar, S. N. and Chopra, I. C. (1956) Gfossary ofIndian Medicinal Plants, p. 139. CUR, New Delhi.
1329
3. The Wealth of India (1959) Raw Materials V, p. 159. CSIR, New Delhi. 4. Chaudhury, R. R. and Haq, M. (1980) Bull. Med. Echnohoc. Res. I, 408. 5. Saluia, A. K. and Santani, D. D. (1981) Indian Drugs 19. 127. 6 Julian, P. K., Pikl, J. and Dawsbn, R. (1938) J. Am. Chem. sot. 60, 77. 7 Mayo, P. de and Starrat, A. N. (1962) Can. J. Chem. 40,788. 8. Mayo, P. de and Starrat, A. N. (1962) Can. J. Chem. 40, 1632. 9. Guise, G. B., Ritchie, E. and Taylor, W. C. (1962) Aust. J. Chem. 15, 314. IO. Eade, R. A., Ellis, J., Harper, P. and Simes, J. J. H. (1969) J. Chem. Commun. 579. 11. Branch, G. B., Burgess, D. V., Dunstan, P. J., Foo, L. Y., Green, G. H., Mack, J. P. G., Ritchie, E. and Taylor, W. C. (1972) Aust. J. Chem. 25, 2209. 12. Roitman, J. N. and Jurd, L. (1978) Phytochemistry 17, 491. 13. Baxter, R. L. and Walkinshaw, D. M. (1988) Phytochemistry 27, 2350. 14. Eade, R. A., Ellis, J., and Simes, J. J. H. (1967) Aust. J. Chem. 20, 2737. 15. Burbage, M. B., Jewers, K., Eade, R. A., Harper, P. and Simes, J. J. H. (1970) J. Gem. Commun. 814. 16. Burbage, M. B., Jewers, K., Eade, R. A., Harper, P. and Simes, J. J. H. (1971) J. Chem. Commun. 195. 17. Takahashi, K. and Takani, M. (1978) Chem Pharm. Bull. 26, 2689. 18. Budzikeiwiez, M., Wilson, J. M. and Djerassi, C. (1963) J. Am. Chem. Sot. 85, 3688. 19. Potier, P., Das, B. C., Bui, A.-M., Janot, M.-M., Pourrat, A. and Pourrat, H. (1966) Bull. Sot. Chim. Fr. 3458. 20. Raja Rao, K. V., Rao, L. J. M. and Prakasa Rao, N. S. (1989) Planta Med. (in press). 21. Gopalsamy, N., Vargas, D., Gneno, J., Ricand, C. and Hostettmann, K. (1988) Phytochemistry 27, 3593. 22. Goh, E. M., Williams, A. H. and Holland, P. T. (1978) J. Chem. Sot. Perkin Trans I 1560. 23. Mayo, P. de., and Starratt, A. N. (1961) Tetrahedron Letters 259. 24. Sims, J. J. and Petters Jr, J. A. (1976) Phytochemistry 15, 1096. 25. Wenkert, E., Baddeley, G. V., Burtitt, I. R. and Moreno, L. N. (1978) Org. Magn. Reson. 11, 337. 26. Halshall, T. G. and Aplin, R. T. (1964) in Progress in the Chemistry of Organic Natural Products (Zechmeister, R.L., ed.), Vol. 22, p. 153. Springer, New York.