title: Stereoselective synthesis of some methyl-substituted steroid hormones and their in vitro cytotoxic activity against human gastric cancer cell line MGC-803.
abstract: 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.
authors.affiliation: 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.
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Wenwei
authors.initials: W
authors.lastname: Qiu
authors.forename: Zhengfeng
authors.initials: Z
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Luo
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.forename: Juan
authors.initials: J
authors.lastname: Xie
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D004967:Estrogens; D006728:Hormones; D013256:Steroids