Time Economical Total Synthesis of (-)-Oseltamivir
Time Economical Total Synthesis of (-)-Oseltamivir
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DOI：
10.1021/acs.orglett.6b01595
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发表时间：
2016-07-15
期刊：
影响因子：
5.2
通讯作者：
Ogasawara, Shin
中科院分区：
文献类型：
--
作者：
Hayashi, Yujiro;Ogasawara, Shin
在一个反应器中，经五步反应，在60 min内完成了（-）-奥司他韦的全合成。关键问题之一是通过用快速差向异构化步骤取代冗长的反应步骤来减少步骤数量。由三种试剂，即二苯基脯氨醇硅醚，硫脲，和酸组成的催化体系，开发了一种快速的不对称迈克尔反应具有良好的非对映体和对映体选择性。所有反应不仅在收率和选择性方面，而且在反应时间方面进行了优化。
A time economical 60 min total synthesis of (-)-oseltamivir was accomplished in a single reaction vessel over five steps. One of the key issues is reduction in the number of steps by eliminating lengthy reaction steps with substitution of a rapid epimerization step. A catalytic system consisting of three reagents, namely, diphenylprolinol silyl ether, thiourea, and acid, was developed for a rapid asymmetric Michael reaction with excellent diastereo- and enantioselectivities. All reactions were optimized in terms of not only yield and selectivity but also reaction time.