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Teupernin D, a neo-clerodane diterpenoid from Teucrium pernyi
Vol. 33, No. Printed in Great Britain Pkyrockemistry,
TEUPERNIN
3, pp. 716 717, 1993
003l-9422193$6.00+ 00
Q 1993Pergamon Press Ltd
D, A lVEO-CLERODANE DITERPENOID PERNYI
FROM
TEUCRIWM
SUN DI-AN and Lr GUANG-YI Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China (Received 14 October 1992)
Key Word Index-Teucrium
pernyi; Labiatae; neo-clerodane diterpenoids; teupernin D.
Abstract-A new neo-clerodane diterpenoid, teupernin D, was isolated from the whole plant of Teucrium prnyi together with the known diterpenoids teucvidin, teuflin, montanin D and teuscorodonin. The structure of teupernin D was mainly established by spectroscopic means and comparison with related compounds.
J = 8.6, 13.2 Hz), an AB system of 2H-19 (64.70,4.79, d, J = 11 Hz) and a methoxy group (63.58, s). The signals at
INTRODUCTiON
In previous communications, both we [l] and Xie Ning et [23 reported the isolation of three new neo-clerodane diterpenoids, teupernin A, B and C from the whole plant of Teucrium pernyi, Franch. In this communication, we report the isolation of the four known diterpenoids teucvidin [3], teuflin [4,5], montanin D [6,7] and teuscorodonin [S], and a new neo-clerodane diterpenoid teupernin D, from the same plant. al.
RESULTS AND DISCUSSION
Teupernin D (1) has a molecular formula CZ1Hz60, ([M]‘390,1684calc. 390.1678) and its IR spectrum shows absorptions of a furan ring (3140, 1505, 875 cm- ‘), a hydroxyl group (3400 cm - ‘) and an a&unsaturated ester grdup (1685 cm- ‘). The ‘HNMR spectrum (Table 1) contains characteristic signals for a B-substituted furan ring (two a-furan protons at 67.78 and 7.72 and one /I-furan proton at 66.58), a secondary C-17 methyl group (81.10, d, J = 5.85 Hz), an ABX system of H-12a (65.58, t, J = 8.6 Hz), H-lla (61.63, dd, J=8.6, 13.2 Hz) and H-lib (62.50, dd,
63.52 (s) and 5.91 (br s) disappear after addition of D20. Thus teupernin D has two hydroxyl groups. In the COLOC spectrum C-18 shows long range coupling with - OMe. Therefore, the - OMe group must be located at C-18. One of the hydroxyl groups is at C-19 as found in teuscorodonin, while the other is at C-6. The proton at C6 shows a broad singlet at 6 5.16, this indicates that the hydroxyl group at C-6 must have b-orientation. The 13C NMR spectrum of 1 (Table 2) is similar to that of teuscorodonin. The relative configuration of teupernin D was determined by NOE experiments. Irradiation of Me-17 (6 1.10) caused NOE enhancement of the signal for H-14 (S6.58),
15
Table 1. ‘H NMR data of teupernin D (500 MHz, pyridine-d,, TMS as int. standard) H 3 6u 7a 7b 10s
lla llb 12c? 14 15 16
Me-17 19a 19b 21
6.95 t (3.54) 5.16 br s 2.50 m 1.91 m 2.16dd (2, 13.4) 1.63 dd (8.6, 13.2) 2.50 dd (8,6, 13.2) 5.58 t (8.6) 6.58 br s 7.72br s 7.78br s 1.10 d (5.85) 4.79d (11)
4.70 d (11) 3.58 s
Values in parentheses are coupling constants in Hz.
1 716
717
Short Reports Table 2. *3C NMR data of teupernin D (125 MHz, pyridine-d,, TMS as int. standard) C 1 2 3 4 5 6 7 8 9 10 11
C 19.8t 26.5t 140.0d 137.5 s 49.2s 66.9d 35.4t 35.5 d 52.5 s 46.0 d 44.5 t
12 13 14 15 16 17 18 19 20 21
72.2 127.0 108.7 144.5 140.5 17.4 169.8 65.0 178.0 51.6
d s d d d
q s
t s
q
whereas the signal for the H-12 (65.57) was not affected. This behaviour indicated that the furan ring and the Me17 of teupernin D are on the same side of the lactone ring [93. Irradiation of H-6 caused NOE enhancement of the signals for H-19a, b, thus H-6 has an a-orientation. The porientation of H-10 was confirmed from the NOE enhancement of H-lla, b on irradiation of H-10. The absolute configuration of teupernin D has not been established. However, as all of the diterpenoids isolated from Teucrium species [lo] belong to the neoclerodane series, teupernin D should also have the same neo-clerodane skeleton. Thus, the structure of teupernin D was deduced as 1.
din (200 mg), teuflin (20 mg), montain D (80 mg), teuscorodonin (150 mg) and teupernin D (20 mg). The known diterpenoids were identified by their physical and spectroscopic data. Teupernin D. Mp 186188” (MeOH); TRvEi cm-i: 3400,3140,2950,1755,1685,1640,1610,1505,1475,1440, 1415,1360,1320,1275,1240,1180,1160,1120,1085,1060, 1020,990,970,935,920,875,855,820,800,795,760,720; ‘HNMR: Table 1; “C NMR: Table 2; EIMS m/z (rel. int.): 390 CM]’ (29), 372 (3), 342 (18), 340 (5), 328 (3.5), 311 (22), 310 (lOO), 289 (9), 265 (22), 247 (lo), 234 (6), 201 (9), 161(14), 143 (21), 105 (21), 96 (65), 95 (90), 94 (31), 91 (31), 81 (36); HRMS: 390.1684 talc. 390.1678, Cz1Hz607. Acknowledgements-We are grateful to Mr Liu XiaoLong, Anhui Chinese Medical School, for his kind assistance in the collecting and identification of the plant material, and to NSFC for financial support. REFERENCES
1. Sun Di-An and Li Guang-Yi (1991) Chin. Chem. Lett 2, 539. 2. Xie Ning, Min Zhi-Da, Zhao Shuo-Xun, Wu Bing, Zheng Qi-Tai and Zhang Pei (199 1) P hytochemistry 30, 1963. 3. Uchida, I., Fujita, T. and Fujita, E. (1975) Tetruhe&on 31, 841. 4. Node, M., Sai, M. and Fujita, E. (1981) Phytochemistry 20, 757.
5. Savona, G., Paternostro,
M. P. and Piozzi, F. (1979)
J. Chem. Sot. Perkin Truns I 19 15. EXPERIMENTAL
Mps: uncorr. Plant materials were collected in August 1988 from Anhui Province (south east China). Extraction and isolation. Dried and powdered whole plants of Teucrium pernyi (1.6 kg) were extracted with EtOH (95%). The syrup (208 g) was extracted with petrol, Me,CO and BuOH, respectively. The Me&O extract (50 g) was repeatedly subjected to silica gel CC using petrol-Me&O and CHCl,-MeOH mixts as eluating solvents. Eight diterpenoids were obtained, teupernin A (150 mg), teupernin B (20 mg), teupernin C (8 mg), teucvi-
6. Malakov, P. Y., Papanov, G. Y. and Mollov, M. (1978) 2. Natwjbrsch. 33B, 1142. 7. Gacs-Baitz, E., Kajtar, M., Papanov, G. Y. and Malakov, P. Y. (1982) Heterocycles 19, 539. 8. Marco, J., Rodriguez, B., Pascual, C., Savona, G. and Piozzi, F. (1983) Phytochemistry 22, 727. 9. Pascual, C., Fernandez, P., Garcia-Alvarez, M. C., Marco, J. L., Femandez-Gadea, F., de la Terre, M. C., Hueso-Rodriguez, J. A., Rodriguez, B., Bruno, M., Patemostro, M., Piozzi, F. and Savona, G. (1986) Phytochemistry 25, 715.
10. piozzi,
F., Rodriguez,
Heterocycks 25, 807.
B. and Savona,
G. (1987)
TEUPERNIN
3, pp. 716 717, 1993
003l-9422193$6.00+ 00
Q 1993Pergamon Press Ltd
D, A lVEO-CLERODANE DITERPENOID PERNYI
FROM
TEUCRIWM
SUN DI-AN and Lr GUANG-YI Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing 100050, China (Received 14 October 1992)
Key Word Index-Teucrium
pernyi; Labiatae; neo-clerodane diterpenoids; teupernin D.
Abstract-A new neo-clerodane diterpenoid, teupernin D, was isolated from the whole plant of Teucrium prnyi together with the known diterpenoids teucvidin, teuflin, montanin D and teuscorodonin. The structure of teupernin D was mainly established by spectroscopic means and comparison with related compounds.
J = 8.6, 13.2 Hz), an AB system of 2H-19 (64.70,4.79, d, J = 11 Hz) and a methoxy group (63.58, s). The signals at
INTRODUCTiON
In previous communications, both we [l] and Xie Ning et [23 reported the isolation of three new neo-clerodane diterpenoids, teupernin A, B and C from the whole plant of Teucrium pernyi, Franch. In this communication, we report the isolation of the four known diterpenoids teucvidin [3], teuflin [4,5], montanin D [6,7] and teuscorodonin [S], and a new neo-clerodane diterpenoid teupernin D, from the same plant. al.
RESULTS AND DISCUSSION
Teupernin D (1) has a molecular formula CZ1Hz60, ([M]‘390,1684calc. 390.1678) and its IR spectrum shows absorptions of a furan ring (3140, 1505, 875 cm- ‘), a hydroxyl group (3400 cm - ‘) and an a&unsaturated ester grdup (1685 cm- ‘). The ‘HNMR spectrum (Table 1) contains characteristic signals for a B-substituted furan ring (two a-furan protons at 67.78 and 7.72 and one /I-furan proton at 66.58), a secondary C-17 methyl group (81.10, d, J = 5.85 Hz), an ABX system of H-12a (65.58, t, J = 8.6 Hz), H-lla (61.63, dd, J=8.6, 13.2 Hz) and H-lib (62.50, dd,
63.52 (s) and 5.91 (br s) disappear after addition of D20. Thus teupernin D has two hydroxyl groups. In the COLOC spectrum C-18 shows long range coupling with - OMe. Therefore, the - OMe group must be located at C-18. One of the hydroxyl groups is at C-19 as found in teuscorodonin, while the other is at C-6. The proton at C6 shows a broad singlet at 6 5.16, this indicates that the hydroxyl group at C-6 must have b-orientation. The 13C NMR spectrum of 1 (Table 2) is similar to that of teuscorodonin. The relative configuration of teupernin D was determined by NOE experiments. Irradiation of Me-17 (6 1.10) caused NOE enhancement of the signal for H-14 (S6.58),
15
Table 1. ‘H NMR data of teupernin D (500 MHz, pyridine-d,, TMS as int. standard) H 3 6u 7a 7b 10s
lla llb 12c? 14 15 16
Me-17 19a 19b 21
6.95 t (3.54) 5.16 br s 2.50 m 1.91 m 2.16dd (2, 13.4) 1.63 dd (8.6, 13.2) 2.50 dd (8,6, 13.2) 5.58 t (8.6) 6.58 br s 7.72br s 7.78br s 1.10 d (5.85) 4.79d (11)
4.70 d (11) 3.58 s
Values in parentheses are coupling constants in Hz.
1 716
717
Short Reports Table 2. *3C NMR data of teupernin D (125 MHz, pyridine-d,, TMS as int. standard) C 1 2 3 4 5 6 7 8 9 10 11
C 19.8t 26.5t 140.0d 137.5 s 49.2s 66.9d 35.4t 35.5 d 52.5 s 46.0 d 44.5 t
12 13 14 15 16 17 18 19 20 21
72.2 127.0 108.7 144.5 140.5 17.4 169.8 65.0 178.0 51.6
d s d d d
q s
t s
q
whereas the signal for the H-12 (65.57) was not affected. This behaviour indicated that the furan ring and the Me17 of teupernin D are on the same side of the lactone ring [93. Irradiation of H-6 caused NOE enhancement of the signals for H-19a, b, thus H-6 has an a-orientation. The porientation of H-10 was confirmed from the NOE enhancement of H-lla, b on irradiation of H-10. The absolute configuration of teupernin D has not been established. However, as all of the diterpenoids isolated from Teucrium species [lo] belong to the neoclerodane series, teupernin D should also have the same neo-clerodane skeleton. Thus, the structure of teupernin D was deduced as 1.
din (200 mg), teuflin (20 mg), montain D (80 mg), teuscorodonin (150 mg) and teupernin D (20 mg). The known diterpenoids were identified by their physical and spectroscopic data. Teupernin D. Mp 186188” (MeOH); TRvEi cm-i: 3400,3140,2950,1755,1685,1640,1610,1505,1475,1440, 1415,1360,1320,1275,1240,1180,1160,1120,1085,1060, 1020,990,970,935,920,875,855,820,800,795,760,720; ‘HNMR: Table 1; “C NMR: Table 2; EIMS m/z (rel. int.): 390 CM]’ (29), 372 (3), 342 (18), 340 (5), 328 (3.5), 311 (22), 310 (lOO), 289 (9), 265 (22), 247 (lo), 234 (6), 201 (9), 161(14), 143 (21), 105 (21), 96 (65), 95 (90), 94 (31), 91 (31), 81 (36); HRMS: 390.1684 talc. 390.1678, Cz1Hz607. Acknowledgements-We are grateful to Mr Liu XiaoLong, Anhui Chinese Medical School, for his kind assistance in the collecting and identification of the plant material, and to NSFC for financial support. REFERENCES
1. Sun Di-An and Li Guang-Yi (1991) Chin. Chem. Lett 2, 539. 2. Xie Ning, Min Zhi-Da, Zhao Shuo-Xun, Wu Bing, Zheng Qi-Tai and Zhang Pei (199 1) P hytochemistry 30, 1963. 3. Uchida, I., Fujita, T. and Fujita, E. (1975) Tetruhe&on 31, 841. 4. Node, M., Sai, M. and Fujita, E. (1981) Phytochemistry 20, 757.
5. Savona, G., Paternostro,
M. P. and Piozzi, F. (1979)
J. Chem. Sot. Perkin Truns I 19 15. EXPERIMENTAL
Mps: uncorr. Plant materials were collected in August 1988 from Anhui Province (south east China). Extraction and isolation. Dried and powdered whole plants of Teucrium pernyi (1.6 kg) were extracted with EtOH (95%). The syrup (208 g) was extracted with petrol, Me,CO and BuOH, respectively. The Me&O extract (50 g) was repeatedly subjected to silica gel CC using petrol-Me&O and CHCl,-MeOH mixts as eluating solvents. Eight diterpenoids were obtained, teupernin A (150 mg), teupernin B (20 mg), teupernin C (8 mg), teucvi-
6. Malakov, P. Y., Papanov, G. Y. and Mollov, M. (1978) 2. Natwjbrsch. 33B, 1142. 7. Gacs-Baitz, E., Kajtar, M., Papanov, G. Y. and Malakov, P. Y. (1982) Heterocycles 19, 539. 8. Marco, J., Rodriguez, B., Pascual, C., Savona, G. and Piozzi, F. (1983) Phytochemistry 22, 727. 9. Pascual, C., Fernandez, P., Garcia-Alvarez, M. C., Marco, J. L., Femandez-Gadea, F., de la Terre, M. C., Hueso-Rodriguez, J. A., Rodriguez, B., Bruno, M., Patemostro, M., Piozzi, F. and Savona, G. (1986) Phytochemistry 25, 715.
10. piozzi,
F., Rodriguez,
Heterocycks 25, 807.
B. and Savona,
G. (1987)