中文摘要：

以Orlistat为先导化合物,利用Auto Dock进行计算机模拟对接,在对接结果中选择能量较低的6个结构进行合成与抗肿瘤活性筛选。以orlistat为原料,经2步反应制得苄基（2S,3S,5S）-2-己基-3,5-二羟基十六酸酯（2）;再经4步反应获得（3S,4S）-3-己基-4-[（S）-2-羟基十三烷基]氧杂环丁烷-2-酮（5）;5在EDCI作用下与酸经缩合反应合成了4个计新型人脂肪酸合酶抑制剂（6a～6d）,其中6b～6d为新化合物,其结构经1H NMR,13C NMR和HR-MS（ESI）表征。体外初步活性测试表明：（S）-1-[（1S,2S）-3-己基-4-氧代氧杂环丁烷-2-基]十三烷-2-烟酸酯（6a）对MDA-MB-231细胞有较好的抑制作用,其IC50为11.72μmol·m L-1,优于Orlistat（21.5μmol·m L-1）。

英文摘要：

With orlistat as the pilot, six compounds with low-energy structures were chosen by computer stimulation for further synthesis and a ntineoplastic activity screening using AutoDock. Benzyl （2S, 3S ,5S） -2-hexyl-3,5-dihydroxyhexadecanoate （2） was prepared by two steps of reaction from Orlistat. （3S,4S） -3-hexyl-4-[ （S） -2-hydroxytridecyl] oxetan-2-one （ 5 ） was prepared by four steps of reaction from 2. Human fatty acid synthase inhibitors（6a - 6d） were obtained from 5 by condensation reaction with corresponding acid in the presence of EDCI, Among them 6b - 6d were novel compounds. The structures were characterized by t H NMR, 13C NMR and HR-MS （ESI）. In vitro test results showed that（S） -1-[ （2S,3S） -3-hexyl4-oxooxetan-2-yl] tridecan-2-yl nicotinate（6a） exhibited better inhibito- ry activity against fatty acid synthase with IC50 of 11.72 μmol·mL-1, which is better than Orlistat （21.5 μmol · mL - 1 ）.