14β-侧链紫杉醇类似物的合成

14β-侧链紫杉醇类似物的合成

尹大力, 刘瑞武, 王东辉, 郭积玉, 梁晓天^*, 关口喜功, 龟尾一弥

1.中国医学科学院中国协和医科大学药物研究所, 北京 100050
2.大正制药株式会社, 日本琦玉 330

收稿日期:1998-12-14 修回日期:1999-06-03 出版日期:1999-12-15 发布日期:1999-12-15
通讯作者: 梁晓天*

Synthesis of Analogues of Paclitaxel with 14β-Side Chain from Sinenxan A

Yin Dali, Liu Ruiwu, Wang Donghui, Guo Jiyu, Liang Xiaotian^*, Yoshinori Sekiguchi, Kazuya Kameo

1.Institute of Materia Medica, China Academy of Medical Sciences acd Peking Union Medical College, Beijing 100050;
2.Taisho Pharmaceutical Co.Lid 403 Youshion-Cho 1-Chome Ohmiya-shi, Saitama, 330, Japan

Received:1998-12-14 Revised:1999-06-03 Online:1999-12-15 Published:1999-12-15
Contact: Liang Xiaotian*

摘要/Abstract

摘要： SinenxanA(2)是一从红豆杉组织培养物中分离得到的具有紫杉醇母核A/B/C环骨架的化合物。以该化合物为起始原料, 通过4,20-双键合成D-环, 在14β-位引入侧链等合成了1,7,9,13-脱氧-14β-侧链紫杉醇类似物4和5。这两个化合物在体外活性实验中, 对KB, A2780和HCT-8细胞株的细胞毒性比紫杉醇显著降低; 10μmol·L^-1浓度下对微管蛋白聚合没有作用。

关键词: Sinenxan A, C-14β侧链紫杉醇类似物, 半合成

Abstract: Sinenxan A (2), isolated from tissue culture, possesses an A/B/C ring skeletonwithout 1,7,9,13-oxygen functionality of paclitaxel (1). Two 1,7,9,13-deoxy, C-14β side chain analogues 4 and 5 of 1 were synthesized from 2 by incorporating the 4,20-double bond into the D-ring and introducing the side chain at 14β position. Compounds 4 and 5 showed significantly decreasedactivity in the cytotoxicity assay in vitro against KB, A2780, and HCT-8. In tubulin assembly assaythey did not show any activity at 10 μmol.L^-1.

Key words: Sinenxan A, Sinenxan A, C-14β side chain paclitaxel analogues, C-14β side chain paclitaxel analogues, Semisynthesis, Semisynthesis

Supporting:

尹大力, 刘瑞武, 王东辉, 郭积玉, 梁晓天^*, 关口喜功, 龟尾一弥. 14β-侧链紫杉醇类似物的合成[J]. .

Yin Dali, Liu Ruiwu, Wang Donghui, Guo Jiyu, Liang Xiaotian^*, Yoshinori Sekiguchi, Kazuya Kameo. Synthesis of Analogues of Paclitaxel with 14β-Side Chain from Sinenxan A[J]. .

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