摘要
富马酸经溴加成,对甲氧基苄胺化保护,三光气闭环及脱水反应制得(3aS,6aR)-1,3-双(4-甲氧苄基)-二氢-1H-呋喃并[3,4-d]咪唑-2,4,6(6aH)-三酮(12),12经奎宁催化不对称醇解、高区域选择性还原,硫代反应制得(+)-生物素关键中间体(3aS,6aR)-1,3-双(4-甲氧苄基)-四氢-1H-噻吩并[3,4-d]咪唑-2,4-二酮,总收率44%。
An asymmetric synthesis of （3 aS,6aR） - 1,3-bis （4-methoxybenzyl） -tetrahydro- 1H-thieno [3,4- d]imidazole-2,4-dione, the key intermediate of （＋）-biotin, was achieved from fumaric acid by bromine addition, condensation, cyclization with triphosgene and dehydration to give （3aS,6aR）-1,3-bis （4-methoxybenzyl）-dihydro-1H- furo [3,4-d] imidazole-2,4,6 （6all）-trione （12）, which was subjected to catalytic asymmetric alcoholysis, regioselective reduction and thiolation with an overall yield of 44 %.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2014年第10期919-923,共5页
Chinese Journal of Pharmaceuticals
