Stereoselective synthesis of some methyl-substituted steroid hormones and their in vitro cytotoxic activity against human gastric cancer cell line MGC-803.
A series of 3-, 7-, 15-, and 16-methyl-substituted steroid analogs were synthesized via a highly stereoselective 1,6-conjugate addition. Under the catalysis of CuBr, AlMe(3) reacted with four steroid dienone precursors to afford either the corresponding alpha-epimer of C-3 and C-7 methyl-substituted steroids as the major products, and the ratio of alpha/beta was up to 10/1. No beta-epimer has been detected for methyl addition at C-16. However, under the same reaction conditions, enantioselective methyl addition at C-15 afforded the 15beta-epimer as the major product. The preliminary SAR analysis showed that the methyl substituents at C-7alpha and C-15beta positions lead to a dramatical increase in potency against human gastric cancer cell line MGC-803.
Li
Chun
C
Institute of Medicinal Chemistry, Department of Chemistry, Institute of Biomedical Sciences, School of Life Sciences, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China.
Qiu
Wenwei
W
Yang
Zhengfeng
Z
Luo
Jian
J
Yang
Fan
F
Liu
Mingyao
M
Xie
Juan
J
Tang
Jie
J
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D004967:Estrogens / Q000737:chemistry; D006728:Hormones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008745:Methylation; D013237:Stereoisomerism; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000473:pathology*; D013379:Substrate Specificity
D000970:Antineoplastic Agents; D004967:Estrogens; D006728:Hormones; D013256:Steroids