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Cardiac glycosides from erysimum cheiranthoides
Phytochemistry Vol. 49, No. 6, pp. 1801±1803, 1998 # 1998 Published by Elsevier Science Ltd. All rights reserved Printed in Great Britain 0031-9422/98/$ - see front matter
PII: S0031-9422(98)00264-7
CARDIAC GLYCOSIDES FROM ERYSIMUM CHEIRANTHOIDES ZHEN-HUAN LEI, ZHE-XION JIN, YING-LI MA, BAO-SHAN TAI, QI KONG, SHOJI YAHARA$ and TOSHIHIRO NOHARA$* Department of Traditional Chinese Medicine, Heilongjang Institute of Commerce, 138 Tongda St., Daoli, Harbin, China and $Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862, Japan (Received 20 January 1998)
Key Word IndexÐErysimum cheiranthoides; Cruciferae; cardiac glycoside; cheiranthoside; strophanthidin. AbstractÐTwo new cardiac glycosides were isolated from the seeds of Erysimum cheiranthoides. Their structures were characterized as strophanthidin glycosides of 3-O-a-L-rhamnopyranosyl-(1 4 4)-3-O-acetylb-D-digitoxopyranosyl and 3-O-b-D-glucpyranosyl-(1 4 4)-a-L-rhamnopyranosyl-(1 4 4)-3-O-acetyl-b-Ddigitoxopyranosyl. # 1998 Published by Elsevier Science Ltd. All rights reserved
INTRODUCTION
Erysimum cheiranthoides L. is distributed over the northern world and is used as a folk medicine in China for treating cardiac diseases; weak cardio palmus, edema, and dyspepsia, etc. [1]. In a previous paper, it was reported that the ethanolic extract of this crude drug has the function of strengthening heart action and reducing blood pressure [2]. Clinical observations indicated that the injection of the extract prepared from the aerial part of this crude drug facilitated heart function, slowing down the heart rate and reducing the blood pressure [3]. Concerning the chemical ingredient, Makarevich et al. [4] isolated and characterized several cardenolides, erysimin, corchoroside, strophantin-b, helveticosol, erysimosol, erycordine and erychrozol from the seeds of this plant growing in Russia [4]. In a foregoing paper, we also reported three new cardenolides together with olitoriside and erysimoside [5]. In a continuing study on the cardenolide in the seeds, we have obtained two additional cardiac glycosides, named cheiranthosides IV and V, so we here report their chemical structures.
RESULTS AND DISCUSSION
Cheiranthoside IV (1) obtained as a white powder, [a]D +27.38 (MeOH), showed a quasi molecu*Author to whom correspondence should be addressed.
lar ion at m/z 721 [M±H]ÿ. Its 1H NMR spectrum displayed signals due to 18-Me at d 1.01, 6-Me of two 6-deoxysugars at d 1.35 (d, J = 6.1 Hz) and 1.66 (d, J = 5.5 Hz), one acetyl group at d 2.03, 17-H at d 2.78 (1H, br d, J = 8.0 Hz), 21-H2 at d 5.03, 5.29 (AB q, J = 17.7 Hz), two anomeric protons at d 5.12 (d, J = 9.2 Hz), and 5.42 (s), 22-H at d 6.13 (s), 19-CHO at d 10.41. On the other hand, the 13C NMR spectrum showed the presence of 35 carbons, among which 23 carbons originated from strophanthidin and 6 carbons were due to a terminal rhamnopyranosyl moiety which could be assigned with superimposable chemical shifts on those of cheiranthoside III [5]. The remaining 8 carbon signals were composed of a mono-acetyl group at d 20.9 and 170.2 and a 2,6-didesoxy hexopyranosyl moiety at d 97.1, 37.0, 70.8, 78.8, 69.6 and 18.5, which were attributable to signals due to the respective C-1, C-2 (ÿ2.4 ppm), C-3 (+2.0 ppm), C-4 (ÿ3.5 ppm), C-5, and C-6 of a 4-O-substituted-3-O-acetyl-digitoxohexosyl moiety by comparison with those of cheiranthoside III. Therefore, compound 1 was characterized as 3-O-aL-rhamnopyranosyl-(1 4 4)-3-O-acetyl-b-D-digitoxopyranosyl strophanthidin. Cheiranthoside V (2), obtained as a white powder, [a]D +10.28 (MeOH), showed a quasi molecular ion peak at m/z 883 [M±H]ÿ in the negative FAB±mass spectrum. The 1H NMR spectrum showed signals due to 18-Me at d 1.00, 6-Me of two 6-deoxysugars at d 1.32 (d, J = 6.1 Hz) and
1801
1802
Short Report
1.71 (d, J = 6.1 Hz), one acetyl group at d 2.00, 17-H at d 2.78 (1H, br d, J = 9.2 Hz), 21-H2 at d 5.02, 5.29 (AB q, J = 18.3 Hz), three anomeric protons at d 5.11 (dd, J = 1.8, 9.2 Hz), 5.20 (d, J = 7.9 Hz), and 5.37 (s), methine proton at d 5.67 (d, J = 3.1 Hz) adjacent to the acetyl group, 22-H at d 6.13 (s), 19-CHO at d 10.40 (s). The 13C NMR spectrum of 2 showed 43 carbon signals, among which 23 were assigned to an aglycone, strophanthidine, 8 to a 4-O-substituted-3-O-acetyl-digitoxohexosyl moiety, 6 to a terminal glucopyranosyl moiety, and the remaining 6 carbons could be assigned to the C-1, C-2, C-3 (+1.3 ppm), C-4 (+11.2 ppm), C-5 (+1.7 ppm), C-6 of a 4-Osubstituted rhamnopyranosyl moiety by comparison with those of cheiranthoside IV (1). Therefore, the chemical structure of 2 was characterized as 3-O-b-D-glucopyranosyl-(1 4 4)-a-L-rhamnopyranosyl-(1 4 4)-3-O-acetyl-b-D-digitoxopyranosyl strophanthidin. It is worth noting that these cardiac glycosides have a linkage combination between thamnose and acetyldigitoxose which is common in cardiac glycosides.
EXPERIMENTAL
General Optical rotations were taken with a JASCO DIP360 digital polarimeter. 1H (400 MHz) and 13C (100 MHz) NMR: with TMS as an internal standard. FAB and EI±MS: JEOL JMS DX-303 HF mass spectrometer. TLC was performed on precoated silica gel 60 F254 (Merck) and detection was achieved by spraying 10% H2SO4 following by heating. CC: silica gel (270±400 mesh, Fuji Silysia
Chemical Ltd.) and MCI gel CHP-20P (Mitsubishi Chemical Ind.). Extraction and isolation The seeds (2.5 kg) of Erysimum cheiranthoides L. were extracted with MeOH and the extract (189 g) was partitioned between n-hexane and H2O. The aq. layer (123 g) was subjected to MCI gel CHP 20P CC eluted with water, 40% MeOH, 60% MeOH, 80% MeOH and MeOH. The 60% eluate (18 g) was subjected to Sephadex LH-20, Chromatorex ODS and silica gel CC to provide cheiranthoside IV (1, 24 mg). The 80% eluate (15 g) was subjected to silica gel and Chromatorex ODS CC to aord cheiranthoside V (2, 14 mg). Cheiranthoside IV (1) A white powder, a28 D +27.38 (c = 0.80. MeOH), Negative FAB±MS m/z: 721 [M±H]ÿ, 679 [M± CH3CO]ÿ. 1H NMR (pyridine-d5) d: 1.01 (3H, s, 18Me), 1.35 (3H, d, J = 6.1 Hz, dig 6-Me), 1.66 (3H, d, J = 5.5 Hz, rha 6-Me), 2.03 (3H, s, dig 3-OAc), 2.78 (1H, br, d, J = 8.0 Hz, 17-H), 5.03, 5.29 (each 1H, d, J = 17.7 Hz, 21-H2), 5.12 (1H, d, J = 9.2 Hz, dig 1-H), 5.42 (1H, s, rha 1-H), 5.74 (1H, br, d, J = 3.1 Hz, dig 3-H), 6.13 (1H, s, 22-H), 10.41 (1H, s, 19-CHO). 13C NMR (pyridine-d5) d: 18.4, 25.5, 75.5, 36.5, 73.8, 36.6, 24.8, 41.9, 39.6, 55.3, 22.6, 39.6, 49.8, 84.4, 32.1, 27.2, 51.1, 16.0, 208.4, 175.6, 73.6, 117.8, 174.4 (C-1±23). 97.1, 37.0, 70.8, 78.8, 69.6, 18.5, (dig C-1±6), 104.3, 72.3, 72.6, 73.6, 70.5, 18.5 (rha C-1±6), 20.9 (dig 3-OCOCH3), 170.17 (dig 3-OCOCH3). Cheiranthoside V (2) A white powder, a17 D +10.28 (c 0.61, MeOH), Negative FAB±MS m/z: 883 [M±H]ÿ. 1H NMR
Short Report
(pyridine-d5) d: 1.00 (3H, s, 18-Me), 1.32 (3H, d, J = 6.1 Hz, dig 6-Me), 1.71 (3H, d, J = 6.1 Hz, rha 6-Me), 2.00 (3H, s, dig 3-OAc), 2.78 (1H, d, J = 9.2 Hz, 17-H), 5.02 (1H, d, J = 18.3 Hz, 21H2), 5.11 (1H, dd, J = 1.8, 9.2 Hz, dig 1-H), 5.20 (1H, d, J = 7.9 Hz, glc 1-H), 5.29 (1H, d, J = 18.3 Hz, 21-H2), 5.37 (1H, s, rha 1-H), 5.67 (1H, d, J = 3.1 Hz, dig 3-H), 6.13 (1H, s, 22-H), 10.40 (1H, s, 19-CHO). 13C NMR (pyridine-d5) d: 18.3, 25.5, 75.4, 36.4, 73.8, 36.5, 24.7, 41.8, 39.6, 55.3, 22.6, 39.6, 49.7, 84.3, 32.0, 27.1, 51.0, 15.9, 208.4, 175.6, 73.6, 117.7, 174.4 (C-1±23), 97.6, 36.9, 70.2, 79.4, 69.5, 18.3 (dig C-1±6), 103.6, 72.3, 71.3, 84.8, 68.8, 18.3 (rha C-1±6), 106.6, 76.1, 78.4, 71.7, 78.4, 62.4 (glc C-1±6), 20.9 (dig 3-OCOCH3), 170.1 (dig 3-OCOCH3).
1803 REFERENCES
1. Zhu, Y. C., Plantae Medicinales Chinae Boreali-Orientalis. Heilongjiang Science and Technology Publishing House, 1989, p. 463. 2. Group of Pharmacological Sciences in Heilongjiang College of Traditional Chinese Medicine, Acta Chinese Medicine and Pharmacology, 1977, 1, 27. 3. Liu, Z. Z., Jiang, S. Q. and Wang, P., Acta Chinese Medicine and Pharmacology, 1978, 2, 42. 4. Makarevich, I. F. and Kolesnikov, D. G., Khim. Prir. Seodin., 1965, 5, 363. 5. Lei, Z. H., Yahara, S. and Nohara, T., Phytochemistry, 1996, 41, 1187.
PII: S0031-9422(98)00264-7
CARDIAC GLYCOSIDES FROM ERYSIMUM CHEIRANTHOIDES ZHEN-HUAN LEI, ZHE-XION JIN, YING-LI MA, BAO-SHAN TAI, QI KONG, SHOJI YAHARA$ and TOSHIHIRO NOHARA$* Department of Traditional Chinese Medicine, Heilongjang Institute of Commerce, 138 Tongda St., Daoli, Harbin, China and $Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862, Japan (Received 20 January 1998)
Key Word IndexÐErysimum cheiranthoides; Cruciferae; cardiac glycoside; cheiranthoside; strophanthidin. AbstractÐTwo new cardiac glycosides were isolated from the seeds of Erysimum cheiranthoides. Their structures were characterized as strophanthidin glycosides of 3-O-a-L-rhamnopyranosyl-(1 4 4)-3-O-acetylb-D-digitoxopyranosyl and 3-O-b-D-glucpyranosyl-(1 4 4)-a-L-rhamnopyranosyl-(1 4 4)-3-O-acetyl-b-Ddigitoxopyranosyl. # 1998 Published by Elsevier Science Ltd. All rights reserved
INTRODUCTION
Erysimum cheiranthoides L. is distributed over the northern world and is used as a folk medicine in China for treating cardiac diseases; weak cardio palmus, edema, and dyspepsia, etc. [1]. In a previous paper, it was reported that the ethanolic extract of this crude drug has the function of strengthening heart action and reducing blood pressure [2]. Clinical observations indicated that the injection of the extract prepared from the aerial part of this crude drug facilitated heart function, slowing down the heart rate and reducing the blood pressure [3]. Concerning the chemical ingredient, Makarevich et al. [4] isolated and characterized several cardenolides, erysimin, corchoroside, strophantin-b, helveticosol, erysimosol, erycordine and erychrozol from the seeds of this plant growing in Russia [4]. In a foregoing paper, we also reported three new cardenolides together with olitoriside and erysimoside [5]. In a continuing study on the cardenolide in the seeds, we have obtained two additional cardiac glycosides, named cheiranthosides IV and V, so we here report their chemical structures.
RESULTS AND DISCUSSION
Cheiranthoside IV (1) obtained as a white powder, [a]D +27.38 (MeOH), showed a quasi molecu*Author to whom correspondence should be addressed.
lar ion at m/z 721 [M±H]ÿ. Its 1H NMR spectrum displayed signals due to 18-Me at d 1.01, 6-Me of two 6-deoxysugars at d 1.35 (d, J = 6.1 Hz) and 1.66 (d, J = 5.5 Hz), one acetyl group at d 2.03, 17-H at d 2.78 (1H, br d, J = 8.0 Hz), 21-H2 at d 5.03, 5.29 (AB q, J = 17.7 Hz), two anomeric protons at d 5.12 (d, J = 9.2 Hz), and 5.42 (s), 22-H at d 6.13 (s), 19-CHO at d 10.41. On the other hand, the 13C NMR spectrum showed the presence of 35 carbons, among which 23 carbons originated from strophanthidin and 6 carbons were due to a terminal rhamnopyranosyl moiety which could be assigned with superimposable chemical shifts on those of cheiranthoside III [5]. The remaining 8 carbon signals were composed of a mono-acetyl group at d 20.9 and 170.2 and a 2,6-didesoxy hexopyranosyl moiety at d 97.1, 37.0, 70.8, 78.8, 69.6 and 18.5, which were attributable to signals due to the respective C-1, C-2 (ÿ2.4 ppm), C-3 (+2.0 ppm), C-4 (ÿ3.5 ppm), C-5, and C-6 of a 4-O-substituted-3-O-acetyl-digitoxohexosyl moiety by comparison with those of cheiranthoside III. Therefore, compound 1 was characterized as 3-O-aL-rhamnopyranosyl-(1 4 4)-3-O-acetyl-b-D-digitoxopyranosyl strophanthidin. Cheiranthoside V (2), obtained as a white powder, [a]D +10.28 (MeOH), showed a quasi molecular ion peak at m/z 883 [M±H]ÿ in the negative FAB±mass spectrum. The 1H NMR spectrum showed signals due to 18-Me at d 1.00, 6-Me of two 6-deoxysugars at d 1.32 (d, J = 6.1 Hz) and
1801
1802
Short Report
1.71 (d, J = 6.1 Hz), one acetyl group at d 2.00, 17-H at d 2.78 (1H, br d, J = 9.2 Hz), 21-H2 at d 5.02, 5.29 (AB q, J = 18.3 Hz), three anomeric protons at d 5.11 (dd, J = 1.8, 9.2 Hz), 5.20 (d, J = 7.9 Hz), and 5.37 (s), methine proton at d 5.67 (d, J = 3.1 Hz) adjacent to the acetyl group, 22-H at d 6.13 (s), 19-CHO at d 10.40 (s). The 13C NMR spectrum of 2 showed 43 carbon signals, among which 23 were assigned to an aglycone, strophanthidine, 8 to a 4-O-substituted-3-O-acetyl-digitoxohexosyl moiety, 6 to a terminal glucopyranosyl moiety, and the remaining 6 carbons could be assigned to the C-1, C-2, C-3 (+1.3 ppm), C-4 (+11.2 ppm), C-5 (+1.7 ppm), C-6 of a 4-Osubstituted rhamnopyranosyl moiety by comparison with those of cheiranthoside IV (1). Therefore, the chemical structure of 2 was characterized as 3-O-b-D-glucopyranosyl-(1 4 4)-a-L-rhamnopyranosyl-(1 4 4)-3-O-acetyl-b-D-digitoxopyranosyl strophanthidin. It is worth noting that these cardiac glycosides have a linkage combination between thamnose and acetyldigitoxose which is common in cardiac glycosides.
EXPERIMENTAL
General Optical rotations were taken with a JASCO DIP360 digital polarimeter. 1H (400 MHz) and 13C (100 MHz) NMR: with TMS as an internal standard. FAB and EI±MS: JEOL JMS DX-303 HF mass spectrometer. TLC was performed on precoated silica gel 60 F254 (Merck) and detection was achieved by spraying 10% H2SO4 following by heating. CC: silica gel (270±400 mesh, Fuji Silysia
Chemical Ltd.) and MCI gel CHP-20P (Mitsubishi Chemical Ind.). Extraction and isolation The seeds (2.5 kg) of Erysimum cheiranthoides L. were extracted with MeOH and the extract (189 g) was partitioned between n-hexane and H2O. The aq. layer (123 g) was subjected to MCI gel CHP 20P CC eluted with water, 40% MeOH, 60% MeOH, 80% MeOH and MeOH. The 60% eluate (18 g) was subjected to Sephadex LH-20, Chromatorex ODS and silica gel CC to provide cheiranthoside IV (1, 24 mg). The 80% eluate (15 g) was subjected to silica gel and Chromatorex ODS CC to aord cheiranthoside V (2, 14 mg). Cheiranthoside IV (1) A white powder, a28 D +27.38 (c = 0.80. MeOH), Negative FAB±MS m/z: 721 [M±H]ÿ, 679 [M± CH3CO]ÿ. 1H NMR (pyridine-d5) d: 1.01 (3H, s, 18Me), 1.35 (3H, d, J = 6.1 Hz, dig 6-Me), 1.66 (3H, d, J = 5.5 Hz, rha 6-Me), 2.03 (3H, s, dig 3-OAc), 2.78 (1H, br, d, J = 8.0 Hz, 17-H), 5.03, 5.29 (each 1H, d, J = 17.7 Hz, 21-H2), 5.12 (1H, d, J = 9.2 Hz, dig 1-H), 5.42 (1H, s, rha 1-H), 5.74 (1H, br, d, J = 3.1 Hz, dig 3-H), 6.13 (1H, s, 22-H), 10.41 (1H, s, 19-CHO). 13C NMR (pyridine-d5) d: 18.4, 25.5, 75.5, 36.5, 73.8, 36.6, 24.8, 41.9, 39.6, 55.3, 22.6, 39.6, 49.8, 84.4, 32.1, 27.2, 51.1, 16.0, 208.4, 175.6, 73.6, 117.8, 174.4 (C-1±23). 97.1, 37.0, 70.8, 78.8, 69.6, 18.5, (dig C-1±6), 104.3, 72.3, 72.6, 73.6, 70.5, 18.5 (rha C-1±6), 20.9 (dig 3-OCOCH3), 170.17 (dig 3-OCOCH3). Cheiranthoside V (2) A white powder, a17 D +10.28 (c 0.61, MeOH), Negative FAB±MS m/z: 883 [M±H]ÿ. 1H NMR
Short Report
(pyridine-d5) d: 1.00 (3H, s, 18-Me), 1.32 (3H, d, J = 6.1 Hz, dig 6-Me), 1.71 (3H, d, J = 6.1 Hz, rha 6-Me), 2.00 (3H, s, dig 3-OAc), 2.78 (1H, d, J = 9.2 Hz, 17-H), 5.02 (1H, d, J = 18.3 Hz, 21H2), 5.11 (1H, dd, J = 1.8, 9.2 Hz, dig 1-H), 5.20 (1H, d, J = 7.9 Hz, glc 1-H), 5.29 (1H, d, J = 18.3 Hz, 21-H2), 5.37 (1H, s, rha 1-H), 5.67 (1H, d, J = 3.1 Hz, dig 3-H), 6.13 (1H, s, 22-H), 10.40 (1H, s, 19-CHO). 13C NMR (pyridine-d5) d: 18.3, 25.5, 75.4, 36.4, 73.8, 36.5, 24.7, 41.8, 39.6, 55.3, 22.6, 39.6, 49.7, 84.3, 32.0, 27.1, 51.0, 15.9, 208.4, 175.6, 73.6, 117.7, 174.4 (C-1±23), 97.6, 36.9, 70.2, 79.4, 69.5, 18.3 (dig C-1±6), 103.6, 72.3, 71.3, 84.8, 68.8, 18.3 (rha C-1±6), 106.6, 76.1, 78.4, 71.7, 78.4, 62.4 (glc C-1±6), 20.9 (dig 3-OCOCH3), 170.1 (dig 3-OCOCH3).
1803 REFERENCES
1. Zhu, Y. C., Plantae Medicinales Chinae Boreali-Orientalis. Heilongjiang Science and Technology Publishing House, 1989, p. 463. 2. Group of Pharmacological Sciences in Heilongjiang College of Traditional Chinese Medicine, Acta Chinese Medicine and Pharmacology, 1977, 1, 27. 3. Liu, Z. Z., Jiang, S. Q. and Wang, P., Acta Chinese Medicine and Pharmacology, 1978, 2, 42. 4. Makarevich, I. F. and Kolesnikov, D. G., Khim. Prir. Seodin., 1965, 5, 363. 5. Lei, Z. H., Yahara, S. and Nohara, T., Phytochemistry, 1996, 41, 1187.