- Email: [email protected]
Phenolics from needles of himalayan Taxus baccata
Phytochmistry,
Vol. 33, No. 6, pp. 1489-1491,1993
0031~9422/93 .$6.00+0.00
0 1993PergamonPressLtd
Printedin Great Britain.
PHENOLICS
FROM NEEDLES B.
DAS,~
OF HIMALAYAN
TAXUS BACCATA*
M. TAKHI, K. V. N. S. SRINIVASand J. S. YADAV
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500007, India (Receioed 2 December 1992)
Key Word Index--Taxus glucoside; taxuside.
baccata; Taxaceae; phenolics; lignan; 3-demethyl-( -)-secoisolariciresinol;
Abstract-Chemical investigation on the needles of the Himalayan yew, Taxus baccata, has resulted in the isolation of several phenolic compounds including 3-demethyl-( - )-secoisolariciresinol, a new lignan, and taxuside, a new phenolic glucoside. The structures of the new compounds were derived from their spectral data and chemical transformations.
INTRODUCTION The taxane diterpenoids and related alkaloids having promising anti-tumour activity are widely distributed [l] in Tuxus species. During our recent search for such bioactive compounds in the needles of the Himalayan yew, Taxus baccata L. we have isolated the phenolic arylpropanols (l-3) and arylbutanols (4-6) [2], lignans (7-10) and the phenolic glucosides, betuloside (15) [3] and taxuside (16), along with a complex mixture of taxane derivatives [4]. Herein we report on the structure elucidation of the new lignan, 3-demethyl-( - )-secoisolariciresinol (7) and of the new phenolic glucoside named taxuside (16). RESULTSANDDISCUSSION 3-Demethyl-( -)-secoisolariciresinol(7) was isolated as crystals. Its IR spectrum (vi:; cn-‘: 3455, 1610, 1515) indicated it to be an aromatic hydroxy derivative. The 200 MHz ‘H NMR spectrum and the mass spectral fragmentation pattern of 7 clearly suggested a secoisolariciresin01 lignan-type skeleton [S]. The lignan 7 formed a pentaacetate (11) with acetic anhydride and pyridine, and a trimethyl ether (12) with diazomethane. The latter on treatment with acetic anhydride and pyridine afforded a diacetate (13). These reactions suggested the presence of three phenolic and two alcoholic hydroxyls in 7. The similar nature of the five hydroxyls was also observed in isotaxiresinol(l0) [6,7], another lignan constituent of the same species. The structure of 7 was confirmed as 3demethyl-( -)-secoisolariciresinol by the observation that its trimethyl ether (12) was identical in all respects to (-)secoisolariciresinol dimethyl ether [S] produced by the treatment of (-)-secoisolariciresinol (8) with diazomethane. Taxuside (16) was isolated as an amorphous powder which showed strong hydroxyl absorption in its IR *IICT Communication No. 3128. tAuthor to whom correspondence should be addressed.
spectrum (~2; cm- I: 3330). The ‘HNMR spectrum (200 MHz, D,O) showed signals for aromatic protons of a trisubstituted aromatic ring at 66.80 (lH, d, J= 8.0 Hz, H-5’), 6.75 (lH, d, J= 1.8 Hz, H-2’) and 6.62 (lH, dd, J =8.0 and 1.8 Hz, H-6’). The spectrum revealed the presence of a glucopyranosyl moiety from the anomeric proton signal at 64.48 (lH, d, J= 7.8 Hz) and six other glucosyl proton signals at 63.45 (lH, dd, J =9.8 and 7.8 Hz, glu H-2), 3.50-3.35 (3H, m, glu H-3, H-4 and H-5), 3.91 (lH, dd, J= 12.0 and 5.5 Hz, glu H-6a) and 3.72 (lH, dd, J = 12.0 and 2.0 Hz, glu H-6b). The coupling constant of the anomeric proton (J = 7.8 Hz) suggested [9] the pconfiguration for the sugar. The other signals of 16 appearedat 63.78(1H,m,H-2),2.65(2H, t,J=7.0 Hz,H,4), 1.98-1.71 (2H, m, H,-3) and 1.10 (3H, d, J=8.0Hz, Me). Taxuside (16) formed a hexaacetate (17) containing two aromatic (62.21,6H) and four aliphatic acetyl groups (62.08-1.95, 12H). Acid hydrolysis of the glucoside produced D-ghWse and 4-(3’,4’-dihydroxyphenyl)-2R-butanol(5). Both have been characterized by spectral studies and by direct comparison with authentic samples [2]. The structure of taxuside was thus confirmed as 4-(3’,4’dihydroxyph~yl)-2R-butanol-2-O-B-D-glucopyranoside (la). It should be noted here that the catechol moiety was observed both in the new lignan 7 and in the new glucoside 16. The known phenolic arylpropanols (l-3) and arylbutanols (4-6) [2] and the known lignans, (-)-secoisolariciresin01 (8) [4, 10, 111, ( +)-isolariciresinol (9) [4, 121 and isotaxiresinol (10) [4, 6, 7, lo] were also isolated. The structures of the known compounds were established by comparison of their physical, spectral and chemical properties with those reported in the literature.
EXPERIMENTAL General. Mps: uncorr. CC: silica gel (100-200 mesh). TLC: silica gel G. TLC spots were visualized by exposure to IZ vapour. Acetates and Me ethers were all prepd by
1489
Phenolin from Taxus baccata
1491
-33.5” (CHCl,; c 1.0). The spectral properties of the compound were identical to those reported in the lit. [S].
coned and purified by silica gel CC to provide D-glucose (2 mg), [alis + 54.1” (H,O; c 0.2238).
3-Demethyl-( -)-secoisolariciresinol trimethyl ether diacetate (13). Viscous oil. [a];’ -29.3” (CHCl,; c 0.5518)
Acknowledgements-The
lit.[S] [a]$’ -28” (CHCl,; c 1.0). All spectral data were identical to reported values [S]. Isotaxiresinol trimethyl ether [( +)-isolariciresinol dimethyl ether] (14). Mp 181-182” (MeOH). [a];’ + 12.2
(CHCl,; c 0.4237) lit. [S] mp 176-178” (MeOH), [a]:: + 12.4” (CHCl,; c 0.6). Taxuside hexaacetate (17). Viscous oil. IR ~2:’ cm-‘: 1745. ‘HNMR (200 MHz, CDCl,): 66.82 (lH, d, J =8.0Hz,H-5’),6.77(1H,d,J=1.8Hz,H-2’),6.6O(lH,dd, .J = 8.0 and 1.8 Hz, H-6’), 5.56 (lH, t, J = 9.0 Hz, glu H-4), 5.04 (lH, t, J=9.0 Hz, glu H-3), 4.95 (lH, dd, J=9.0 and 7.8 Hz, glu H-2), 4.50 (lH, d, J=7.0 Hz, glu H-l), 4.19 (lH, dd, J= 12.0 and 4.5 Hz, glu H-6a), 4.08 (lH, dd, J = 12.0 and 2.5 Hz, glu H-6b), 3.75 (lH, m, H-2), 3.70 (lH, m, glu H-5), 2.60 (2H, t, J=7.0Hz, H,-4), 2.21 (BH, s, 2 OAc), 2.08-1.95 (12H, 4 OAc), 1.92-1.68 (2H, m, H,-3), 1.05 (3H, d, J= 8.0 Hz, Me). MS m/z (rel. int.): 512 [M -42]+(2), 331 (lo), 164 (lOO), 149 (25), 137 (lo), 123 (72). Acid hydrolysis of taxuside (16). Taxuside (10 mg) was refluxed with 2 N H,SO, (5 ml) for 2 hr. The reaction mixt. was diluted with H,O, extracted with CHCI, (3 x 20 ml), coned and purified by CC over silica gel to give 4-(3’, 4’-dihydroxyphenyl)-2R-butanol(5) [2] as a viscous mass -18.1” (EtOH; ~0.3124). ‘HNMR (3 mg). C~li’ (200 MHz, CDCl,): 66.82 (lH, d, J=8.0 Hz, H-5’), 6.75 (lH, d, J= 1.8 Hz, H-2’), 6.64 (lH, dd, 3=8.0 and 1.8 Hz, H-6’), 3.82 (lH, m, H-2), 2.65 (2H, t, J=7.0Hz, H,-4), 1.82-1.64 (2H, m, H,-3) and 1.21 (3H, d, J = 8.0 Hz, Me). MS m/z (rel. int.): 182 [M]‘(SO), 164 (20), 149 (40) 123 (100). The aq. layer was adjusted to pH 5 with NaHCO,,
authors thank Dr A. V. Rama Rao, Director, for his constant encouragement and Drs R. S. Kapil and T. N. Srivastava, RRL, Jammu-Tawi, India, for the supply of plant material and for their keen interest. REFERENCES
1. Khan, N. U. and Parveen, N. (1987) J. Sci. Ind. Res. 46, 512. 2. Das, B., Takhi, M., Srinivas, K. V. N. S. and Yadav, J. S. (1993) Phytochemistry (in press). 3. Sarkar, S. K., Poddar, G. and Mahato, S. B. (1987) Planta Med. 53, 219. 4. Erdtman, H. and Tsuno, K. (1969) Phytochemistry 8, 931.
5. Fonseca, S. F., Nielsen, L. T. and Ru’veda, E. D. (1979) Phytochemistry 18, 1703. I 6. King, F. E., Jurd, L. and King, T. J. (1952) J. Chem. sot. 17. 7. Majumdar, R. B., Srinivasan, R. and Venkataratnam, K. (1972) Znd. J. Chem. 10,677. 8. Brown, E. and Daugan, A. (1989) Tetrnhedron 45, 141.
9. Gao, F., Wang, H., Mabry, T. J. and Jakupovic, J. (1991) Phytochemistry 30, 553. 10. Erdtman, H. and Tsuno, K. (1969) Acta. Chem. Stand. 23, 202 1. 11. Powell, R. G. and Plattner, R. D. (1976) Phytochemistry 15, 1963.
12. Abe, F. and Yamauchi, T. (1989) Phytochemistry 28, 1737.
Vol. 33, No. 6, pp. 1489-1491,1993
0031~9422/93 .$6.00+0.00
0 1993PergamonPressLtd
Printedin Great Britain.
PHENOLICS
FROM NEEDLES B.
DAS,~
OF HIMALAYAN
TAXUS BACCATA*
M. TAKHI, K. V. N. S. SRINIVASand J. S. YADAV
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500007, India (Receioed 2 December 1992)
Key Word Index--Taxus glucoside; taxuside.
baccata; Taxaceae; phenolics; lignan; 3-demethyl-( -)-secoisolariciresinol;
Abstract-Chemical investigation on the needles of the Himalayan yew, Taxus baccata, has resulted in the isolation of several phenolic compounds including 3-demethyl-( - )-secoisolariciresinol, a new lignan, and taxuside, a new phenolic glucoside. The structures of the new compounds were derived from their spectral data and chemical transformations.
INTRODUCTION The taxane diterpenoids and related alkaloids having promising anti-tumour activity are widely distributed [l] in Tuxus species. During our recent search for such bioactive compounds in the needles of the Himalayan yew, Taxus baccata L. we have isolated the phenolic arylpropanols (l-3) and arylbutanols (4-6) [2], lignans (7-10) and the phenolic glucosides, betuloside (15) [3] and taxuside (16), along with a complex mixture of taxane derivatives [4]. Herein we report on the structure elucidation of the new lignan, 3-demethyl-( - )-secoisolariciresinol (7) and of the new phenolic glucoside named taxuside (16). RESULTSANDDISCUSSION 3-Demethyl-( -)-secoisolariciresinol(7) was isolated as crystals. Its IR spectrum (vi:; cn-‘: 3455, 1610, 1515) indicated it to be an aromatic hydroxy derivative. The 200 MHz ‘H NMR spectrum and the mass spectral fragmentation pattern of 7 clearly suggested a secoisolariciresin01 lignan-type skeleton [S]. The lignan 7 formed a pentaacetate (11) with acetic anhydride and pyridine, and a trimethyl ether (12) with diazomethane. The latter on treatment with acetic anhydride and pyridine afforded a diacetate (13). These reactions suggested the presence of three phenolic and two alcoholic hydroxyls in 7. The similar nature of the five hydroxyls was also observed in isotaxiresinol(l0) [6,7], another lignan constituent of the same species. The structure of 7 was confirmed as 3demethyl-( -)-secoisolariciresinol by the observation that its trimethyl ether (12) was identical in all respects to (-)secoisolariciresinol dimethyl ether [S] produced by the treatment of (-)-secoisolariciresinol (8) with diazomethane. Taxuside (16) was isolated as an amorphous powder which showed strong hydroxyl absorption in its IR *IICT Communication No. 3128. tAuthor to whom correspondence should be addressed.
spectrum (~2; cm- I: 3330). The ‘HNMR spectrum (200 MHz, D,O) showed signals for aromatic protons of a trisubstituted aromatic ring at 66.80 (lH, d, J= 8.0 Hz, H-5’), 6.75 (lH, d, J= 1.8 Hz, H-2’) and 6.62 (lH, dd, J =8.0 and 1.8 Hz, H-6’). The spectrum revealed the presence of a glucopyranosyl moiety from the anomeric proton signal at 64.48 (lH, d, J= 7.8 Hz) and six other glucosyl proton signals at 63.45 (lH, dd, J =9.8 and 7.8 Hz, glu H-2), 3.50-3.35 (3H, m, glu H-3, H-4 and H-5), 3.91 (lH, dd, J= 12.0 and 5.5 Hz, glu H-6a) and 3.72 (lH, dd, J = 12.0 and 2.0 Hz, glu H-6b). The coupling constant of the anomeric proton (J = 7.8 Hz) suggested [9] the pconfiguration for the sugar. The other signals of 16 appearedat 63.78(1H,m,H-2),2.65(2H, t,J=7.0 Hz,H,4), 1.98-1.71 (2H, m, H,-3) and 1.10 (3H, d, J=8.0Hz, Me). Taxuside (16) formed a hexaacetate (17) containing two aromatic (62.21,6H) and four aliphatic acetyl groups (62.08-1.95, 12H). Acid hydrolysis of the glucoside produced D-ghWse and 4-(3’,4’-dihydroxyphenyl)-2R-butanol(5). Both have been characterized by spectral studies and by direct comparison with authentic samples [2]. The structure of taxuside was thus confirmed as 4-(3’,4’dihydroxyph~yl)-2R-butanol-2-O-B-D-glucopyranoside (la). It should be noted here that the catechol moiety was observed both in the new lignan 7 and in the new glucoside 16. The known phenolic arylpropanols (l-3) and arylbutanols (4-6) [2] and the known lignans, (-)-secoisolariciresin01 (8) [4, 10, 111, ( +)-isolariciresinol (9) [4, 121 and isotaxiresinol (10) [4, 6, 7, lo] were also isolated. The structures of the known compounds were established by comparison of their physical, spectral and chemical properties with those reported in the literature.
EXPERIMENTAL General. Mps: uncorr. CC: silica gel (100-200 mesh). TLC: silica gel G. TLC spots were visualized by exposure to IZ vapour. Acetates and Me ethers were all prepd by
1489
Phenolin from Taxus baccata
1491
-33.5” (CHCl,; c 1.0). The spectral properties of the compound were identical to those reported in the lit. [S].
coned and purified by silica gel CC to provide D-glucose (2 mg), [alis + 54.1” (H,O; c 0.2238).
3-Demethyl-( -)-secoisolariciresinol trimethyl ether diacetate (13). Viscous oil. [a];’ -29.3” (CHCl,; c 0.5518)
Acknowledgements-The
lit.[S] [a]$’ -28” (CHCl,; c 1.0). All spectral data were identical to reported values [S]. Isotaxiresinol trimethyl ether [( +)-isolariciresinol dimethyl ether] (14). Mp 181-182” (MeOH). [a];’ + 12.2
(CHCl,; c 0.4237) lit. [S] mp 176-178” (MeOH), [a]:: + 12.4” (CHCl,; c 0.6). Taxuside hexaacetate (17). Viscous oil. IR ~2:’ cm-‘: 1745. ‘HNMR (200 MHz, CDCl,): 66.82 (lH, d, J =8.0Hz,H-5’),6.77(1H,d,J=1.8Hz,H-2’),6.6O(lH,dd, .J = 8.0 and 1.8 Hz, H-6’), 5.56 (lH, t, J = 9.0 Hz, glu H-4), 5.04 (lH, t, J=9.0 Hz, glu H-3), 4.95 (lH, dd, J=9.0 and 7.8 Hz, glu H-2), 4.50 (lH, d, J=7.0 Hz, glu H-l), 4.19 (lH, dd, J= 12.0 and 4.5 Hz, glu H-6a), 4.08 (lH, dd, J = 12.0 and 2.5 Hz, glu H-6b), 3.75 (lH, m, H-2), 3.70 (lH, m, glu H-5), 2.60 (2H, t, J=7.0Hz, H,-4), 2.21 (BH, s, 2 OAc), 2.08-1.95 (12H, 4 OAc), 1.92-1.68 (2H, m, H,-3), 1.05 (3H, d, J= 8.0 Hz, Me). MS m/z (rel. int.): 512 [M -42]+(2), 331 (lo), 164 (lOO), 149 (25), 137 (lo), 123 (72). Acid hydrolysis of taxuside (16). Taxuside (10 mg) was refluxed with 2 N H,SO, (5 ml) for 2 hr. The reaction mixt. was diluted with H,O, extracted with CHCI, (3 x 20 ml), coned and purified by CC over silica gel to give 4-(3’, 4’-dihydroxyphenyl)-2R-butanol(5) [2] as a viscous mass -18.1” (EtOH; ~0.3124). ‘HNMR (3 mg). C~li’ (200 MHz, CDCl,): 66.82 (lH, d, J=8.0 Hz, H-5’), 6.75 (lH, d, J= 1.8 Hz, H-2’), 6.64 (lH, dd, 3=8.0 and 1.8 Hz, H-6’), 3.82 (lH, m, H-2), 2.65 (2H, t, J=7.0Hz, H,-4), 1.82-1.64 (2H, m, H,-3) and 1.21 (3H, d, J = 8.0 Hz, Me). MS m/z (rel. int.): 182 [M]‘(SO), 164 (20), 149 (40) 123 (100). The aq. layer was adjusted to pH 5 with NaHCO,,
authors thank Dr A. V. Rama Rao, Director, for his constant encouragement and Drs R. S. Kapil and T. N. Srivastava, RRL, Jammu-Tawi, India, for the supply of plant material and for their keen interest. REFERENCES
1. Khan, N. U. and Parveen, N. (1987) J. Sci. Ind. Res. 46, 512. 2. Das, B., Takhi, M., Srinivas, K. V. N. S. and Yadav, J. S. (1993) Phytochemistry (in press). 3. Sarkar, S. K., Poddar, G. and Mahato, S. B. (1987) Planta Med. 53, 219. 4. Erdtman, H. and Tsuno, K. (1969) Phytochemistry 8, 931.
5. Fonseca, S. F., Nielsen, L. T. and Ru’veda, E. D. (1979) Phytochemistry 18, 1703. I 6. King, F. E., Jurd, L. and King, T. J. (1952) J. Chem. sot. 17. 7. Majumdar, R. B., Srinivasan, R. and Venkataratnam, K. (1972) Znd. J. Chem. 10,677. 8. Brown, E. and Daugan, A. (1989) Tetrnhedron 45, 141.
9. Gao, F., Wang, H., Mabry, T. J. and Jakupovic, J. (1991) Phytochemistry 30, 553. 10. Erdtman, H. and Tsuno, K. (1969) Acta. Chem. Stand. 23, 202 1. 11. Powell, R. G. and Plattner, R. D. (1976) Phytochemistry 15, 1963.
12. Abe, F. and Yamauchi, T. (1989) Phytochemistry 28, 1737.