苦蘵中Withanolide型化合物的化学成分研究
|
摘要
Withanolide型化合物是一类具有28个碳原子的麦角甾烷型的化合物,其特有的结构是22位与26位碳连接形成一个6内酯环的侧链。Withanolides不仅可以用来表示麦角甾烷型的22,26-内酯,也可以用来表示所有生源相关的化合物。前者是经典型的Withanolide型化合物,后者是非经典型的Withanolide型化合物。
这些化合物主要分布在茄科的几个属中,如Physalis、Withania、Ajuga、Datura、Jaborosa、Dunalia、Salpichroa、Deprea、Solanum、Vassobia、Exodeconus、Hyoscyamus、Iochroma、Discopodium等。其中Physalis(酸浆属)是这类化合物的重要来源。该属植物在世界许多国家具有悠久的药用历史,并且已成为近年来临床研究正在进行的项目。在初步的研究中,已经证实了该属植物对各种肿瘤和白血病细胞有胞毒性,并且还具有抗病原微生物的作用。本课题选用了一种典型的茄科酸浆属植物：Physalis angulata苦蘵(重庆南川县)对此种植物的Withanolide类型化学成分进行系统研究,共分离得到Withanolide型化合物11个,他们分别是physagulins L-0 (1-4), withagulatin A(5), physagulin K(6), withaminimin(7), physagulin J(8), physagulin B(9), pubesenolide(10), physagulin D(11).
通过文献检索及对照,发现化合物1、2、3、4为新化合物。以上化合物的结构鉴定通过IR, 1D,2D-NMR, HRMS,旋光等方法进行确定。对上述的化合物进行抗肿瘤活性测定,发现化合物5和9对人乳腺癌病毒(HCT-116)和非人小肺癌病毒(NCI-H460)有很好的抑制作用。化合物5IC50分别是1.64±0.06μM和1.40±0.04μM,化合物9IC50分别是2.11±0.1μMM和0.43±0.02μM。
Withanolides are structurally diverse steroids with an ergostane skeleton in which C (22) and C (26) are oxidized to form a d-lactone. Withanolides not only represent a d-lactone with C (22) and C (26) oxidized, but also represent all relatived biosynthetic pathways compounds. The former is normal withanolide compounds, the latter is non-normal ones. These compounds are specific for the Solanaceae family, and, in particular, for the genera Physalis、Withania、Ajuga、Datura、Jaborosa、Dunalia、Salpichroa、Deprea、Solanum、Vassobia、Exodeconus、Hyoscyamus、Iochroma、Discopodium and so on. Physalis is the important origin for these compounds. The genera plants have been used in various countries in popular medicine as a treatment for different illnesses, and have become a clinical research project recently. In preliminary research, the results showed that the raw extract of the material possessed anti-tumor activities and anti-leukaemia cell lines activity. In present work, we choosed two kinds of physalis plants:Physalis angulata (Nanchuan County, Chongqing city).The chemical investigation of the methanol extract of its aerial part led to afford 11 withanolides:physagulins L-O (1-4), withagulatin A(5), physagulin K(6), withaminimin(7), physagulin J(8), physagulin B(9), pubesenolide(10), physagulin D(11)。
Compounds 1、2、3、4 are new chemicals. The structures of these compounds were determined by spectral data including IR,1D, 2D-NMR and HRMS spectra. Compounds 1-11 were tested for their antiproliferative activity towards the human colorectal carcinoma (HCT-116) cell line and human non-small cell lung cancer (NCI-H460) cell line. Compound 5 exhibited the highest activity against the HCT-116 cell line, with an IC50 value of 1.64±0.06μM, and compound 9 exhibited the highest activity to NCI-H460 cell line, with an IC50 value of 0.43±0.02μM.
这些化合物主要分布在茄科的几个属中,如Physalis、Withania、Ajuga、Datura、Jaborosa、Dunalia、Salpichroa、Deprea、Solanum、Vassobia、Exodeconus、Hyoscyamus、Iochroma、Discopodium等。其中Physalis(酸浆属)是这类化合物的重要来源。该属植物在世界许多国家具有悠久的药用历史,并且已成为近年来临床研究正在进行的项目。在初步的研究中,已经证实了该属植物对各种肿瘤和白血病细胞有胞毒性,并且还具有抗病原微生物的作用。本课题选用了一种典型的茄科酸浆属植物：Physalis angulata苦蘵(重庆南川县)对此种植物的Withanolide类型化学成分进行系统研究,共分离得到Withanolide型化合物11个,他们分别是physagulins L-0 (1-4), withagulatin A(5), physagulin K(6), withaminimin(7), physagulin J(8), physagulin B(9), pubesenolide(10), physagulin D(11).
通过文献检索及对照,发现化合物1、2、3、4为新化合物。以上化合物的结构鉴定通过IR, 1D,2D-NMR, HRMS,旋光等方法进行确定。对上述的化合物进行抗肿瘤活性测定,发现化合物5和9对人乳腺癌病毒(HCT-116)和非人小肺癌病毒(NCI-H460)有很好的抑制作用。化合物5IC50分别是1.64±0.06μM和1.40±0.04μM,化合物9IC50分别是2.11±0.1μMM和0.43±0.02μM。
Withanolides are structurally diverse steroids with an ergostane skeleton in which C (22) and C (26) are oxidized to form a d-lactone. Withanolides not only represent a d-lactone with C (22) and C (26) oxidized, but also represent all relatived biosynthetic pathways compounds. The former is normal withanolide compounds, the latter is non-normal ones. These compounds are specific for the Solanaceae family, and, in particular, for the genera Physalis、Withania、Ajuga、Datura、Jaborosa、Dunalia、Salpichroa、Deprea、Solanum、Vassobia、Exodeconus、Hyoscyamus、Iochroma、Discopodium and so on. Physalis is the important origin for these compounds. The genera plants have been used in various countries in popular medicine as a treatment for different illnesses, and have become a clinical research project recently. In preliminary research, the results showed that the raw extract of the material possessed anti-tumor activities and anti-leukaemia cell lines activity. In present work, we choosed two kinds of physalis plants:Physalis angulata (Nanchuan County, Chongqing city).The chemical investigation of the methanol extract of its aerial part led to afford 11 withanolides:physagulins L-O (1-4), withagulatin A(5), physagulin K(6), withaminimin(7), physagulin J(8), physagulin B(9), pubesenolide(10), physagulin D(11)。
Compounds 1、2、3、4 are new chemicals. The structures of these compounds were determined by spectral data including IR,1D, 2D-NMR and HRMS spectra. Compounds 1-11 were tested for their antiproliferative activity towards the human colorectal carcinoma (HCT-116) cell line and human non-small cell lung cancer (NCI-H460) cell line. Compound 5 exhibited the highest activity against the HCT-116 cell line, with an IC50 value of 1.64±0.06μM, and compound 9 exhibited the highest activity to NCI-H460 cell line, with an IC50 value of 0.43±0.02μM.
引文
[1]中华本草
[2]M.D.Antoun,D.Abramson,R.L.Tyson,et al.Potenitial antitumor agents. Physalis B and 25,26-epidihydrophysalin C from Witheringia coccolobodies,J.Nat.Prod.,1981,44:579-585.
[3]H.Chiang,S.Jaw and C.Chem. Inhibitory effects of physalin B and physalin F on various human leukemia cells in vitro, Anticancer Res.,1992,12(4):1155-1162.
[4]H.Chiang,S.Jaw and C.Chem,et al.Antitumor agent, physalin F from physalis angulata L., Anticancer Res.,1992,12(3):837-843.
[5]M.Kawai,B.Makion,.H.Yamamura,et al.Cytotoxic activity of physalis and related compounds against Hela cells,Pharmazie,2002,57(5):348-350.
[6]S. Nagafuji, H. Okabe, H. Akahane, F. Abe, Biol. Pharm. Bull. 2004,27(2),193.
[7]K. Shingu, S. Yahara, T. Nohara, H. Okabe, Chem. Pharm. Bull. 1992,40(8),2088.
[8]Y.S.Chin,H.C.Chiang,W.S.Kan,et al. Immun-omodulatory activity of various fractions derived from Physalis angulata L.extract,Am.J.Chin.Med.,1992,20(3～4):233-243.
[9]M.B.Soares,.M.C.Bellintain,I.M.Ribeiro,et al. Inhibition of macrophage activation and lipopolysaccaride-induced death by seco-steriods purified from physalis angulata Eur.J.Pharmacol., 2003,459(1):107-112.
[10]马磊博士论文Withanolides化合物的研究
[11]C. M. Chen, Z. T. Chen, C. H. Hsieh, W. S. Li, S. Y. Wen, Heterocycles 1990,31,1371.
[12]H. E. Gottlieb, M. Cojocaru, S. C. Sinha, M. Saha, Phytochemistry 1987,26,1801.
[13]M. Sahai, J. Nat. Prod.1985,48,474.
[14]S. Mingguzzi, L. E. S. Barota, Y. G. Shin, Phytochemistry 2002, 59,635.
[15]S. Ahmad, A. Malik, R.Yasmin, Phytochemistry 1999,50,647.
[16]A. Monks, D. Scudiero, P. Skehan, R. Shoemaker, J. Natl. Cancer Inst.1991,53,757.
[1]P. Chirsten. Withanolide, Pharm. zeit.,1989,18:129-139
[2]E. Glotter. Withanolides and related ergostane-type steroids, Nat. Prod. Reports 1991,8:415-440
[3]I.Kirson and E. Glotter. Recent developments in naturally occurring ergostane-type steroids, J.Nat. Prod. 1981,44 (6):633-646
[4]中国科学院植物研究所等, 中国植物志,第67分卷第1分册,北京,科学出版社,1978,53-59
[5]N. V. Kovganko and Zh. N. Kashkan. Advances in the chemical synthesis of withanolides. Chem. of Nat.Comp.1997,33(2):133-145
[6]Shinya Nagafuji, Hikaru Okabe, Hiroshige Akahane et al., Trypanocidal constituents in plant withanolides from the aerial parts of Physalis angulata. Bio. Pharm. Bull. 2004,27 (2):193-197
[7]Pir M. Kham, Hafiz R.Nawaz et al., Ajugins C and D, New withanolides from Ajuga parviflora
[8]O. E. Vasina, N. D. Abdullaev, N. K. Abubakirov. Withanolides of Physalis Ⅸ physangulide the first natural 22s-withasteroid. Chem. Nat. Compd.1990,26 (3):304-307
[9]Masao Kawai, Akihide Matsumoto, Bunsho Makino. The structure of P,a neophysalin from Physalis alkekengi. Bull. Chem. Soc. Jpn.1993,66:1299-1300
[11]Bunsho Makino, Masao Kawai, Toichi Ogura et al., Structure revision of Physalin H isolated from Physalis angulata. J.Nat. Prod.1995,58(11):1168-1674
[12]Saeed Ahmad, Abdul Malik, Nighat Afza et al., A new withanolide glycoside from Physalis peruvina. J.Nat. Prod. 1999,62:493-494
[13]M. Manickam, Anjana Sinha-Bagchi, Subhash C. sinha et al., Withanolide of Datura fastuosa leaves. Phytochemistry 1993,34 (3):868-870
[14]G. L. Silva, A. Pacciaroni, J.C. Oberti et al., A pregnane structurally related to withanolides from Physalis viscose. Phytochemistry 1993,34(3):871-873
[15]Anthony C. Waiss Jr., Carl A. Euiger, William F. Haddon et al., Insect inhibitory steroidal saccharide esters from Physalis peruviana. J.Nat. Prod.1993,56 (8):1365-1372
[16]Reiko Sunayama, Masanori Kuroyanagi, Kaoru Umehara et al., Physalin and neophysalins from Physalis alkekengi var francheti and their differentiation inducing activity. Phytochemistry 1993,34 (2):529-533
[17]Masao Kawai, Toichi Ogura, Bunsho Makino et al., Physalins N and O from Physalis alkekengi. Phytochemistry 1992,31 (12):4299-4302
[18]Kazushi Shingu, Shaji Yahara, Toshihiro Nohara et al. Three new withanolides, physalins A,B and D from Physalis angulata L. Chem. Pharm. Bull.1992,40(8):2088-2091
[19]Chiu-Ming Chen, Zong-Tsi Chen, Chiu-Hsiang Hsieh et al., Withangulatin A, A new withanolide from Physalis angulata. Heterocycles 1990,31(7):1371-1375
[20]Kazushi Shingu, Shoji Yahara, Hikaru Okabe et al., Three new withanolides physalins E, F and G from Physal is angulata L. Chem. Pharm. Bull.1992,40 (9):2448-2451
[21]Kazushi Shingu, Mariko Miyagawa, Shoji Yahara et al. Physapruins A and B, two new withanolides from Physalis pruinosa Bailey. Chem. Pharm. Bull.1993,41 (10):1873-1875
[22]Saeed Ahmad, Abdul Malik, Rehana Yasmin. Withanolides from physalis peruviana. Phytochemistry 1999,50:647-651
[23]Laurence N. Dinan, Satyajit D. Sarker, Vladimir Sik. 28-hydroxywithanolide E from Physalis peruviana. Phytochemistry 1997,44(3):509-512
[24]Naoki Asano, Atsushi Kato, Haruhisa Kizu et al.,1β-amino-2α,3β,5β-trihydroxy cycloheptane from Physalis alkekengi var francheti. Phytochemistry 1996,42(3):719-721
[25]G. Sen, H. D. Pathak Phsalin L, a 13,14-seco-16,24-cyclosteroid from Physalis minima. Phytochemistry 1995,39 (5):1245-1246
[26]Kazushi Shingu, Nobuhiro Marubayashi, Ikuhiko Veda et al., Physagulin C, a new withanolide from Physalis angulata L. Chem. Pharm. Bull 1991,39 (6):1591-1593
[27]Saeed Ahmad, Pehana Yasmin, Abdul Malik. New withanolide glycosides from Physalis peruviana L. Chem. Pharm. Bull. 1999,47 (4):477-480
[28]Emma Maldonado, Fernando R. Torres, Mahinda Martinez et al. 18-acetoxywithanolides from Physalis chenopodifolia. Planta Med.2004,70:59-64
[29]A. S. R. Anjaneyulu, D. Satyanarayana Rao. New wi thanol ides from the roots of Withania somnifera. Indian J. of Chemistry 1997,36B:424-433
[30]A. S. R. Anjaneyulu, D. Satyanarayana Rao. A new withanolide from the leaves of Withania somnifera. Indian J. of Chemistry 1997,36B:161-165
[31]Atta-ur-Rahman, S. Arshad Jamal, M. Iqbal Choudhary et al., Two new withanolides from Withania somnifera. Heterocycles 1992,34(4):689-698
[32]Atta-ur-Rahman, S. Arshad Jamal, M. Iqbal Choudhary et al., Two withanolides from Withania somnifera. Phytochem. 1991,30(11):3824-3826
[33]Atta-ur-Rahman, Samina Abbas, Dur-E-Shahwab. New withanolides from withania spp. J.Nat. Prod. 1993,56 (7):1000-1006
[34]Masanori Kuroyanagi, Kazutoshi Shibata, Kaoru Umehara. Cell differentiation inducing steroids from withania somnifera L. (Dun.) Chem.pharm.Bull.1999,47 (11):1646-1649
[35]M. Iqbal Choudhary, Dur-E-Shahwar, Zeba Parveen et al. Antifungal steroidal lactones from Withania coagulance. Phytochem 1995,40(4):1243-1246
[36]Hafiz Rub Nawaz, Abdul Malik, Pir Mohammad Khan et al., Ajugin E and F:two withanolides from Ajuga parviflora. Phytochem.1999,52:1357-1360
[37]Atta-ur-Rahman, Muhammad Shabbir, Muhammad Yousaf et al., Three withanolides from Withania coagulans. Phytochem. 1999,52:1361-1364
[38]Mohammed Au, Mohammed Shuaib, Shahid Husain Ansari. Withanolides from the stem bark of Withania somnifera. Phytochem.1997,44 (6):1163-1168
[39]Atta-ur-Rahman, M. Iqbal Choudhary, Muhammad Yousaf et al., New withanolides from Withania coagulans
[40]Bunsho Makino, Masao Kawai, Kojikito et al., New physalins possessing an additional carbon-carbon bond from Physalis alkekengi var francheti. Tetrahedron 1995,51 (46):12529-12538
[41]Pir Muhammad Khan, Saeed Ahmad, Hafiz Rubnawaz et al., The first reports of a withanolide from the family Labiatae. Phytochem 1999,51:669-671
[42]Victor Fajardo, Frederico Podesta, Maurice Shamma et al., New withanolides from Jaborosa magellanica. J.Nat. Prod. 1991,54(2):554-563
[43]Adriana S. Veleiro, Claudia E. Trocca, Gerardo Burton et al., A phenolic withanolide from Jaborosa leucotricha. Phytochem 1992,31 (7):2550-2551
[44]Rosana I.Misico, Adriana S. Veleiro, Gerardo Burton et al. Withanolides from Jaborosa leucotricha. Phytochem. 1997,45(5):1048
[45]Viviana E. Nicotra, Roberto R. Gil, Clarisa Vaccarini et al., 15,21-cyclowithanolides from Jaborosa Bergii. J.Nat. Prod. 2003,66:1471-1475
[46]M. A. Farboodniay Jahromi, M. Manickam, Mohini Gupta et al., Withametelins F and G, two new withanolides of Datura. J. Chem. Research (s) 1993:234-235
[47]M. Manickam, A.B.Ray. Structure of withatatulin E, a minor withanolide of Datura tatula. Indian J. of Chemistry 1996,35B:1311-1313
[48]Kazushi Shingu, Yoriko Furusawa, Nobuhiro Marubayashi. The structure of daturametelin D. Chem. Pharm. Bull. 1990,38 (10):2866-2867
[49]Mohini Gupta, Anjana Bagchi, Anil B.Ray. Additional withanolides of Datura metel. J.Nat.Prod.1991,54(2):599-602
[50]Mohini Gupta, M.Manickam, Subhash C. Sinha et al. Withanolides of Datura metel. Phytochem 1992,31 (7):2423-2425
[51]M. Manickam, S. B. Awasthi, A. Sinha-Bagchi et al., Withanolides from Datura tatula. Phytochem 1996,41 (3):981-983
[52]Adriana Cirigliano, Adriana S.Veleiro, Juan C.Oberti et al., A 15 β-hydroxywithanolides from Datura ferox.. Phytochem. 1995,40(2):611-613
[53]Manfred Lischewski, Nguyen Thi Bich Hang, Andrea Porzel et al., Withanolides from Dunalia australis. Phytochem 1991,30(12):4184-4186
[54]Manfred Lischewski, Nguyen Thi Bich Hang, Andrea Porzel et al., Withanolide glycosides from Dunalia australis. Phytochem 1992,31 (3):939-942
[55]Gloria L. Silva, Gerardo Burton, Juan C. Oberti. 18,20-hemiacetal-type and other withanolides from Dunalia brachyacantha. J.Nat. Prod.1999,62:949-953
[56]Javier G.Luis, Fernando Echeverri, Antonio G.Gonzalez. Acnistins F-H, withanolides from Dunalia solanacea. Phytochem 1994,36 (3):769-772
[57]M. Cristina Tettamanzi, Adriana S. Veleiro, Juan C. Oberti et al., New Hydroxylated withanolides from Salpichroa origanifolia. J.Nat. Prod.1998,61:338-342
[58]M. Cristina Tettamanzi, Adriana S. Veleiro, Juan C. Oberti et al., Withanolides from Salpichroa origanifolia. J.Nat. Prod. 2001,64:783-786
[59]Adriana S. Veleiro, Juan C. Oberti, Gerardo Burton. A ring-D aromatic withanolide from Salpichroa origanifolia. Phytochem 1992,31 (3):935-937
[60]Adriana S. Veleiro, Gerardo Burton. New withanolides from Salpichroa origanifolia. J.Nat.Prod.1994,57 (12):1741-1745
[61]Javier G. Luis, Fernando Echeverri, Winston Quinones et al. Withajardins, withanolides with a new type of skeleton structure of withajardins A, B,C and D, absolute configuration of withajardinn C. Tetrahedron 1994,50(4):1217-1226
[62]Fernando Echeverri, Winston Quinones, Fernando Torres et al., Withajardin E, a withanolide from Deprea orinocensis.
[63]Xing-Hua Zhu, Masanao Takagi, Tsuyoshi Ikeda et al., Withanolide-type steroids from Solanum cilistum. Phytochem 2001,56:741-745
[64]Xing-Hua Zhu, Jun Ando, Masanao Takagi, et al., Six new withanolide-type steroids from the leaves of Solanum cilistum.
[65]Rosana I. Misico, Roberto R.Gil, Juan C.Oberti Withanolides from Vassobia lorentzii J.Nat. Prod.2000,63:1329-1332
[66]Roberto R.Gil, Posana I. Misico, Ignacio R. Sotes et al., 16-Hydroxylated withanolides from Exodeconus maritimus J.Nat. Prod.1997,60:568-572
[67]Pir Muhammad Khan, Abdul Malik, Saeed Ahmad et al.,Withanolides from Ajuga parviflora J.Nat. Prod 1999,62,1290-1292
[68]Cui-Ying Ma, Ian D.Williams, Chun-Tao Che Withanolides from Hyoscyamus niger Seeds J. Nat. Prod.1999,62,1445-1447
[69]Dorothee Alfonso, Ilias Kapetanidis Withanolides from Iochroma Gesnerioides Phytochemistry 1994,36(1):179-183
[70]Solomon Habtemariam, Alexander I. Gray. Withanolides from roots of Discopodium penninervium. Planta Med.1998,64:275-276
[71]Solomon Habtemariam, Brian W. Skelton, Peter G. Waterman et al.,17-Epiacnistin-A, a further withanolide from the leaves of Discopodium penninervium. J. Nat; Prod.2000,63:512-513
[2]M.D.Antoun,D.Abramson,R.L.Tyson,et al.Potenitial antitumor agents. Physalis B and 25,26-epidihydrophysalin C from Witheringia coccolobodies,J.Nat.Prod.,1981,44:579-585.
[3]H.Chiang,S.Jaw and C.Chem. Inhibitory effects of physalin B and physalin F on various human leukemia cells in vitro, Anticancer Res.,1992,12(4):1155-1162.
[4]H.Chiang,S.Jaw and C.Chem,et al.Antitumor agent, physalin F from physalis angulata L., Anticancer Res.,1992,12(3):837-843.
[5]M.Kawai,B.Makion,.H.Yamamura,et al.Cytotoxic activity of physalis and related compounds against Hela cells,Pharmazie,2002,57(5):348-350.
[6]S. Nagafuji, H. Okabe, H. Akahane, F. Abe, Biol. Pharm. Bull. 2004,27(2),193.
[7]K. Shingu, S. Yahara, T. Nohara, H. Okabe, Chem. Pharm. Bull. 1992,40(8),2088.
[8]Y.S.Chin,H.C.Chiang,W.S.Kan,et al. Immun-omodulatory activity of various fractions derived from Physalis angulata L.extract,Am.J.Chin.Med.,1992,20(3～4):233-243.
[9]M.B.Soares,.M.C.Bellintain,I.M.Ribeiro,et al. Inhibition of macrophage activation and lipopolysaccaride-induced death by seco-steriods purified from physalis angulata Eur.J.Pharmacol., 2003,459(1):107-112.
[10]马磊博士论文Withanolides化合物的研究
[11]C. M. Chen, Z. T. Chen, C. H. Hsieh, W. S. Li, S. Y. Wen, Heterocycles 1990,31,1371.
[12]H. E. Gottlieb, M. Cojocaru, S. C. Sinha, M. Saha, Phytochemistry 1987,26,1801.
[13]M. Sahai, J. Nat. Prod.1985,48,474.
[14]S. Mingguzzi, L. E. S. Barota, Y. G. Shin, Phytochemistry 2002, 59,635.
[15]S. Ahmad, A. Malik, R.Yasmin, Phytochemistry 1999,50,647.
[16]A. Monks, D. Scudiero, P. Skehan, R. Shoemaker, J. Natl. Cancer Inst.1991,53,757.
[1]P. Chirsten. Withanolide, Pharm. zeit.,1989,18:129-139
[2]E. Glotter. Withanolides and related ergostane-type steroids, Nat. Prod. Reports 1991,8:415-440
[3]I.Kirson and E. Glotter. Recent developments in naturally occurring ergostane-type steroids, J.Nat. Prod. 1981,44 (6):633-646
[4]中国科学院植物研究所等, 中国植物志,第67分卷第1分册,北京,科学出版社,1978,53-59
[5]N. V. Kovganko and Zh. N. Kashkan. Advances in the chemical synthesis of withanolides. Chem. of Nat.Comp.1997,33(2):133-145
[6]Shinya Nagafuji, Hikaru Okabe, Hiroshige Akahane et al., Trypanocidal constituents in plant withanolides from the aerial parts of Physalis angulata. Bio. Pharm. Bull. 2004,27 (2):193-197
[7]Pir M. Kham, Hafiz R.Nawaz et al., Ajugins C and D, New withanolides from Ajuga parviflora
[8]O. E. Vasina, N. D. Abdullaev, N. K. Abubakirov. Withanolides of Physalis Ⅸ physangulide the first natural 22s-withasteroid. Chem. Nat. Compd.1990,26 (3):304-307
[9]Masao Kawai, Akihide Matsumoto, Bunsho Makino. The structure of P,a neophysalin from Physalis alkekengi. Bull. Chem. Soc. Jpn.1993,66:1299-1300
[11]Bunsho Makino, Masao Kawai, Toichi Ogura et al., Structure revision of Physalin H isolated from Physalis angulata. J.Nat. Prod.1995,58(11):1168-1674
[12]Saeed Ahmad, Abdul Malik, Nighat Afza et al., A new withanolide glycoside from Physalis peruvina. J.Nat. Prod. 1999,62:493-494
[13]M. Manickam, Anjana Sinha-Bagchi, Subhash C. sinha et al., Withanolide of Datura fastuosa leaves. Phytochemistry 1993,34 (3):868-870
[14]G. L. Silva, A. Pacciaroni, J.C. Oberti et al., A pregnane structurally related to withanolides from Physalis viscose. Phytochemistry 1993,34(3):871-873
[15]Anthony C. Waiss Jr., Carl A. Euiger, William F. Haddon et al., Insect inhibitory steroidal saccharide esters from Physalis peruviana. J.Nat. Prod.1993,56 (8):1365-1372
[16]Reiko Sunayama, Masanori Kuroyanagi, Kaoru Umehara et al., Physalin and neophysalins from Physalis alkekengi var francheti and their differentiation inducing activity. Phytochemistry 1993,34 (2):529-533
[17]Masao Kawai, Toichi Ogura, Bunsho Makino et al., Physalins N and O from Physalis alkekengi. Phytochemistry 1992,31 (12):4299-4302
[18]Kazushi Shingu, Shaji Yahara, Toshihiro Nohara et al. Three new withanolides, physalins A,B and D from Physalis angulata L. Chem. Pharm. Bull.1992,40(8):2088-2091
[19]Chiu-Ming Chen, Zong-Tsi Chen, Chiu-Hsiang Hsieh et al., Withangulatin A, A new withanolide from Physalis angulata. Heterocycles 1990,31(7):1371-1375
[20]Kazushi Shingu, Shoji Yahara, Hikaru Okabe et al., Three new withanolides physalins E, F and G from Physal is angulata L. Chem. Pharm. Bull.1992,40 (9):2448-2451
[21]Kazushi Shingu, Mariko Miyagawa, Shoji Yahara et al. Physapruins A and B, two new withanolides from Physalis pruinosa Bailey. Chem. Pharm. Bull.1993,41 (10):1873-1875
[22]Saeed Ahmad, Abdul Malik, Rehana Yasmin. Withanolides from physalis peruviana. Phytochemistry 1999,50:647-651
[23]Laurence N. Dinan, Satyajit D. Sarker, Vladimir Sik. 28-hydroxywithanolide E from Physalis peruviana. Phytochemistry 1997,44(3):509-512
[24]Naoki Asano, Atsushi Kato, Haruhisa Kizu et al.,1β-amino-2α,3β,5β-trihydroxy cycloheptane from Physalis alkekengi var francheti. Phytochemistry 1996,42(3):719-721
[25]G. Sen, H. D. Pathak Phsalin L, a 13,14-seco-16,24-cyclosteroid from Physalis minima. Phytochemistry 1995,39 (5):1245-1246
[26]Kazushi Shingu, Nobuhiro Marubayashi, Ikuhiko Veda et al., Physagulin C, a new withanolide from Physalis angulata L. Chem. Pharm. Bull 1991,39 (6):1591-1593
[27]Saeed Ahmad, Pehana Yasmin, Abdul Malik. New withanolide glycosides from Physalis peruviana L. Chem. Pharm. Bull. 1999,47 (4):477-480
[28]Emma Maldonado, Fernando R. Torres, Mahinda Martinez et al. 18-acetoxywithanolides from Physalis chenopodifolia. Planta Med.2004,70:59-64
[29]A. S. R. Anjaneyulu, D. Satyanarayana Rao. New wi thanol ides from the roots of Withania somnifera. Indian J. of Chemistry 1997,36B:424-433
[30]A. S. R. Anjaneyulu, D. Satyanarayana Rao. A new withanolide from the leaves of Withania somnifera. Indian J. of Chemistry 1997,36B:161-165
[31]Atta-ur-Rahman, S. Arshad Jamal, M. Iqbal Choudhary et al., Two new withanolides from Withania somnifera. Heterocycles 1992,34(4):689-698
[32]Atta-ur-Rahman, S. Arshad Jamal, M. Iqbal Choudhary et al., Two withanolides from Withania somnifera. Phytochem. 1991,30(11):3824-3826
[33]Atta-ur-Rahman, Samina Abbas, Dur-E-Shahwab. New withanolides from withania spp. J.Nat. Prod. 1993,56 (7):1000-1006
[34]Masanori Kuroyanagi, Kazutoshi Shibata, Kaoru Umehara. Cell differentiation inducing steroids from withania somnifera L. (Dun.) Chem.pharm.Bull.1999,47 (11):1646-1649
[35]M. Iqbal Choudhary, Dur-E-Shahwar, Zeba Parveen et al. Antifungal steroidal lactones from Withania coagulance. Phytochem 1995,40(4):1243-1246
[36]Hafiz Rub Nawaz, Abdul Malik, Pir Mohammad Khan et al., Ajugin E and F:two withanolides from Ajuga parviflora. Phytochem.1999,52:1357-1360
[37]Atta-ur-Rahman, Muhammad Shabbir, Muhammad Yousaf et al., Three withanolides from Withania coagulans. Phytochem. 1999,52:1361-1364
[38]Mohammed Au, Mohammed Shuaib, Shahid Husain Ansari. Withanolides from the stem bark of Withania somnifera. Phytochem.1997,44 (6):1163-1168
[39]Atta-ur-Rahman, M. Iqbal Choudhary, Muhammad Yousaf et al., New withanolides from Withania coagulans
[40]Bunsho Makino, Masao Kawai, Kojikito et al., New physalins possessing an additional carbon-carbon bond from Physalis alkekengi var francheti. Tetrahedron 1995,51 (46):12529-12538
[41]Pir Muhammad Khan, Saeed Ahmad, Hafiz Rubnawaz et al., The first reports of a withanolide from the family Labiatae. Phytochem 1999,51:669-671
[42]Victor Fajardo, Frederico Podesta, Maurice Shamma et al., New withanolides from Jaborosa magellanica. J.Nat. Prod. 1991,54(2):554-563
[43]Adriana S. Veleiro, Claudia E. Trocca, Gerardo Burton et al., A phenolic withanolide from Jaborosa leucotricha. Phytochem 1992,31 (7):2550-2551
[44]Rosana I.Misico, Adriana S. Veleiro, Gerardo Burton et al. Withanolides from Jaborosa leucotricha. Phytochem. 1997,45(5):1048
[45]Viviana E. Nicotra, Roberto R. Gil, Clarisa Vaccarini et al., 15,21-cyclowithanolides from Jaborosa Bergii. J.Nat. Prod. 2003,66:1471-1475
[46]M. A. Farboodniay Jahromi, M. Manickam, Mohini Gupta et al., Withametelins F and G, two new withanolides of Datura. J. Chem. Research (s) 1993:234-235
[47]M. Manickam, A.B.Ray. Structure of withatatulin E, a minor withanolide of Datura tatula. Indian J. of Chemistry 1996,35B:1311-1313
[48]Kazushi Shingu, Yoriko Furusawa, Nobuhiro Marubayashi. The structure of daturametelin D. Chem. Pharm. Bull. 1990,38 (10):2866-2867
[49]Mohini Gupta, Anjana Bagchi, Anil B.Ray. Additional withanolides of Datura metel. J.Nat.Prod.1991,54(2):599-602
[50]Mohini Gupta, M.Manickam, Subhash C. Sinha et al. Withanolides of Datura metel. Phytochem 1992,31 (7):2423-2425
[51]M. Manickam, S. B. Awasthi, A. Sinha-Bagchi et al., Withanolides from Datura tatula. Phytochem 1996,41 (3):981-983
[52]Adriana Cirigliano, Adriana S.Veleiro, Juan C.Oberti et al., A 15 β-hydroxywithanolides from Datura ferox.. Phytochem. 1995,40(2):611-613
[53]Manfred Lischewski, Nguyen Thi Bich Hang, Andrea Porzel et al., Withanolides from Dunalia australis. Phytochem 1991,30(12):4184-4186
[54]Manfred Lischewski, Nguyen Thi Bich Hang, Andrea Porzel et al., Withanolide glycosides from Dunalia australis. Phytochem 1992,31 (3):939-942
[55]Gloria L. Silva, Gerardo Burton, Juan C. Oberti. 18,20-hemiacetal-type and other withanolides from Dunalia brachyacantha. J.Nat. Prod.1999,62:949-953
[56]Javier G.Luis, Fernando Echeverri, Antonio G.Gonzalez. Acnistins F-H, withanolides from Dunalia solanacea. Phytochem 1994,36 (3):769-772
[57]M. Cristina Tettamanzi, Adriana S. Veleiro, Juan C. Oberti et al., New Hydroxylated withanolides from Salpichroa origanifolia. J.Nat. Prod.1998,61:338-342
[58]M. Cristina Tettamanzi, Adriana S. Veleiro, Juan C. Oberti et al., Withanolides from Salpichroa origanifolia. J.Nat. Prod. 2001,64:783-786
[59]Adriana S. Veleiro, Juan C. Oberti, Gerardo Burton. A ring-D aromatic withanolide from Salpichroa origanifolia. Phytochem 1992,31 (3):935-937
[60]Adriana S. Veleiro, Gerardo Burton. New withanolides from Salpichroa origanifolia. J.Nat.Prod.1994,57 (12):1741-1745
[61]Javier G. Luis, Fernando Echeverri, Winston Quinones et al. Withajardins, withanolides with a new type of skeleton structure of withajardins A, B,C and D, absolute configuration of withajardinn C. Tetrahedron 1994,50(4):1217-1226
[62]Fernando Echeverri, Winston Quinones, Fernando Torres et al., Withajardin E, a withanolide from Deprea orinocensis.
[63]Xing-Hua Zhu, Masanao Takagi, Tsuyoshi Ikeda et al., Withanolide-type steroids from Solanum cilistum. Phytochem 2001,56:741-745
[64]Xing-Hua Zhu, Jun Ando, Masanao Takagi, et al., Six new withanolide-type steroids from the leaves of Solanum cilistum.
[65]Rosana I. Misico, Roberto R.Gil, Juan C.Oberti Withanolides from Vassobia lorentzii J.Nat. Prod.2000,63:1329-1332
[66]Roberto R.Gil, Posana I. Misico, Ignacio R. Sotes et al., 16-Hydroxylated withanolides from Exodeconus maritimus J.Nat. Prod.1997,60:568-572
[67]Pir Muhammad Khan, Abdul Malik, Saeed Ahmad et al.,Withanolides from Ajuga parviflora J.Nat. Prod 1999,62,1290-1292
[68]Cui-Ying Ma, Ian D.Williams, Chun-Tao Che Withanolides from Hyoscyamus niger Seeds J. Nat. Prod.1999,62,1445-1447
[69]Dorothee Alfonso, Ilias Kapetanidis Withanolides from Iochroma Gesnerioides Phytochemistry 1994,36(1):179-183
[70]Solomon Habtemariam, Alexander I. Gray. Withanolides from roots of Discopodium penninervium. Planta Med.1998,64:275-276
[71]Solomon Habtemariam, Brian W. Skelton, Peter G. Waterman et al.,17-Epiacnistin-A, a further withanolide from the leaves of Discopodium penninervium. J. Nat; Prod.2000,63:512-513