化学
氮丙啶
组合化学
立体化学
对映选择合成
奥司他韦
叠氮化物
区域选择性
缩醛
催化作用
戒指(化学)
有机化学
医学
疾病
2019年冠状病毒病(COVID-19)
病理
传染病(医学专业)
作者
Masakatsu Shibasaki,Motomu Kanai
标识
DOI:10.1002/ejoc.200800033
摘要
Abstract We review here the synthetic strategies for oseltamivir phosphate, an important orally active anti‐influenza drug. The Roche synthesis utilized naturally occurring shikimic acid as a starting material. Introduction of the 1‐ethylpropyloxy (“3‐pentyloxy”) functionality by regioselective reduction of the acetal and iterative ring‐opening reactions with azide to introduce nitrogen functionalities were the key steps. Corey and Fukuyama's syntheses utilized catalytic asymmetricDiels–Alder reactions as the starting points, whereas Shibasaki and Kanai's synthesis began with an asymmetric aziridine‐opening reaction with TMSN 3 catalyzed by a polymetallic gadolinium complex. These three syntheses demonstrate the power of asymmetric catalysis in pharmaceutical synthesis. Although Kann's synthesis required resolution to provide an enantiomerically pure intermediate, the properties of chiral iron–diene complexes were elegantly utilized. Yao and Fang's syntheses started from abundant natural chiral sources: L ‐serine and D ‐xylose, respectively. Specifically, Fang's study identified new analogues of oseltamivir with higher potency against several neuraminidases, including oseltamivir‐resistant mutants. Despite the relatively small molecular size, oseltamivir synthesis highlights an important frontier in organic synthesis.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
科研通智能强力驱动
Strongly Powered by AbleSci AI