5α-孕甾-18-羧酸-γ-内酯衍生物的合成及抗肿瘤活性  

Synthesis and Anti-tumor Proliferation Activities of 5α-Pregnano-18-carboxylic acid-γ-lactone Derivative

作　　者：王立中[1,2] 张茂风 刘竺云[1,2] 卞小琴[1] 段子彧 WANG Li-zhong;ZHANG Mao-feng;LIU Zhu-yun;BIAN Xiao-qin;DUAN Zi-yu(College of Pharmacy,Taizhou Polytechnic College,Taizhou 225300,China;Jiangsu Solid Prepara-tion Engineering Technology Research and Development Center,Taizhou Polytechnic College,Taizhou 225300,China)

机构地区：[1]泰州职业技术学院药学院,江苏泰州225300 [2]泰州职业技术学院江苏省固体制剂工程技术研究开发中心,江苏泰州225300

出　　处：《化学试剂》2021年第10期1353-1357,共5页Chemical Reagents

基　　金：江苏省自然科学基金资助项目(BK20190246);泰州市科技支撑计划农业项目(TN201920);泰州市第五期“311工程”资助项目(RCPY202011)。

摘　　要：以3α-羟基-5α-孕甾-20-酮为原料,经羰基还原、甲基卤化、分子内环合、羟基保护、氧化加成、水解6步反应得到3α,20,20-三羟基-5α-孕甾-18-羧酸-γ-内酯衍生物。目标化合物及中间体经^(1)HNMR、^(13)CNMR、IR以及HR-MS表征。通过细胞增殖抑制实验(MTT法)测定3个代表性化合物对人肺癌细胞(A549)、人卵巢癌细胞(SKOV3)、人胃癌细胞(MKN45)和高转移性人乳腺癌细胞(MDA-MB-435)的体外抑制活性。3α,20,20-三羟基-5α-孕甾-18-羧酸-γ-内酯对这些肿瘤细胞的抑制活性最好,其IC_(50)值分别为23.5(A549)、3.8(SKOV3)、13.1(MKN45)、8.6(MDA-MB-435)μmol/L。A novel derivative of 3α,20,20-trihydroxyl-5α-pregnant-18-carboxylic acid-γ-lactone was synthesized in six steps including carbonyl reduction,methyl halogenation,intramolecular cyclization,hydroxyl protection,oxidative addition,and hydrolysis with the 3α-hydroxy-5α-pregnant-20-one as the starting material.The target compound and intermediates were characterized by^(1)HNMR,^(13)CNMR,IR and HR-MS.Cell proliferation inhibitory assay(MTT method)was used to evaluate the in vitro inhibitory effect of the three representative compounds on human lung cancer cell(A549),human ovarian cancer cell(SKOV3),human gastric cancer cell(MKN45)and highly metastatic breast cancer cell(MDA-MB-435).3α,20,20-Trihydroxy-5α-pregna-18-carboxylic acid-γ-lactone displayed stronger inhibitory activities on these tumor cells than others with IC_(50)values of 23.5(A549),3.8(SKOV3),13.1(MKN45)and 8.6(MDA-MB-435)μmol/L.

关 键 词：5α-孕甾-18-羧酸-γ-内酯 甾体 合成 抗肿瘤 活性 

分 类 号：O624.32[理学—有机化学]