布格呋喃体内代谢产物的合成  

Synthesis of a new metabolite of buagarofuran( AF-5)

作　　者：肖琼 刘畅[2] 尹大力 

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,活性物质发现与适药化北京市重点实验室,北京100050 [2]北京积水潭医院,北京100035

出　　处：《中国药科大学学报》2016年第6期673-677,共5页Journal of China Pharmaceutical University

基　　金：国家“重大新药创制”科技重大专项资助项目(No.2010ZX09401405-001)

摘　　要：布格呋喃(AF-5)是已报道的一类具有抗焦虑活性的精神治疗药物之一,其结构由一个沉香呋喃环骨架和一个正丁基侧链组成。临床药代研究发现其新的代谢产物,推测其结构可能为烷烃链端基的羰酸化产物。为了确证其结构,以中间体(4a R,7R,8a R)-8a-羟基-7-(2-羟丙基-2-基)-4a-甲基八氢萘-2(1氢)-酮为原料,经6步反应,成功合成了目标化合物,总收率16.7%。化合物的结构均经NMR和MS确证。It has been reported that buagarofuran（AF-5）as an anxiolytic drug. It possesses a structural feature including α-agarofuran and the n-butyl side chain. Recently, there is a new metabolite found in clinical study, which is hypothesized that the n-butyl side chain has been oxidized to carboxylic acid. In order to confirm its structure, the target compound was prepared from（4aR, 7R, 8aR）-8a-hydroxy-7-（2-hydroxypropan-2-yl）-4a-methyloctahydronaphthalen-2（1H）-one in a six-step reaction with an overall yield of 16. 7%. The structure is confirmed by NMR and MS.

关 键 词：布格呋喃 AF-5 代谢产物 合成 结构鉴定 

分 类 号：R914.5[医药卫生—药物化学]