摘要
以价廉易得的氟苯和戊二酸为原料,经傅-克反应、酰胺化、酮的还原、偶联和环合等数步反应合成依折麦布,总收率为7.5%.其中,用KRED238全细胞酮还原酶直接还原化合物5的羰基获得了具有S构型的羟基化合物中间体6,该步反应的收率为95%,(S)-羟基de值95.68%,还原反应的立体选择性高.该结果证实了生物催化技术应用于依折麦布合成中的可行性,为依折麦布绿色不对称合成工艺的发展提供了新的思路.
From the cheap raw materials fluorobenzene and pentanedioic acid,ezetimibe has been synthesized by six steps reaction such as Friedel-Crafts reaction,acylation reaction,reduction reaction,coupling reaction and cyclization etc.The total yield of ezetimibe is 7.5%.The key step has been performed by KRED238 ketoreductase from the compound 5and obtained a S configuration intermediate compound 6in a yield of 95%,the dextrose equivalent value is 95.68%.The reduction reaction has been carried out with a high stereoselectivity.The results demonstrate that the biocatalytic technology can be used for the synthesis of ezetimibe.It provides a new way for the development of green asymmetric synthesis of ezetimibe.
出处
《西南师范大学学报（自然科学版）》
CAS
北大核心
2015年第10期173-176,共4页
Journal of Southwest China Normal University(Natural Science Edition)
关键词
依折麦布
酮还原酶
合成
ezetimibe
ketoreductase
synthesis
