四氢苯并噻唑-2-丙酮肟的合成研究  

Synthesis of Tetrahydrobenzothiazole-2-propanone Oximes

作　　者：张瑞泽 张燕芸 段桂运 李洪爽 武夏明[2] ZHANG Rui-ze;ZHANG Yan-yun;DUAN Gui-yun;LI Hong- shuang;WU Xia-ming(Institute of Pharmacology, Taishan Medical University, Tai＇an 271016, China;Affiliated Hospital of Taishan Medical University,Tai＇an 271000,China)

机构地区：[1]泰山医学院药理学研究所,山东泰安271016 [2]泰山医学院附属医院,山东泰安271000

出　　处：《化学试剂》2018年第6期571-575,共5页Chemical Reagents

基　　金：山东省重点研发计划项目(2018GGX109010);国家级大学生创新创业训练计划项目(201710439101);山东省医药卫生科技发展计划项目(2016WS0625);泰安市科技发展计划项目(2015GX2049,2016NS1080)

摘　　要：以2-氯环己酮为起始原料,与硫代甲酰胺进行分子间环合得到4,5,6,7-四氢苯并噻唑,随后与不同取代的环丙醇在AgBF4/K2S2O8体系作用下进行自由基串联式反应,得到酮羰基取代的关键中间体。最后,中间体与盐酸羟胺进行分子间脱水得到两个标题化合物,其结构经~1HNMR、ESI-MS进行确证。采用MTT法初步评价了目标化合物对SHG-44、H1299肿瘤细胞株的抗肿瘤活性。此合成方法具有原料易得、步骤精短、反应效率较高的特点,为后续四氢苯并噻唑-2-丙酮肟类衍生物的合成及抗肿瘤活性评价奠定了基础。4,5,6,7-Tetrahydrobenzothiazole was obtained via intermolecular cyclization of 2-chlorocyclohexanone with thioformamide,which was subsequently reacted with cyclopropanols bearing different substitution patterns in the presence of Ag BF4/K2 S2 O8 system to afford carbonyl-substituted key intermediates.Finally,the key intermediates were subjected to intermolecular dehydration with hydroxylamine hydrochloride to deliver two tetrahydrobenzothiazole-2-propanone oximes.The structures of the compounds were confirmed by1 HNMR and ESI-MS.Furthermore,the two target compounds were evaluated for their antitumor activities against human glioma cell line SHG-44 and human lung cancer cell line H1299 by the method of MTT.This strategy features readily available starting materials,step-economic and high efficiency,which could pave the way for the synthesis of tetrahydrobenzothiazole-2-propanone oxime derivatives and the evaluation of antitumor activity.

关 键 词：四氢苯并噻唑-2-丙酮肟 自由基串联式反应 抗肿瘤活性 合成 

分 类 号：O62[理学—有机化学]