Synthesis of PDE IVb inhibitors. 1. Asymmetric synthesis and stereochemical assignment of (+)- and (-)-7-[3-(cyclopentyloxy)-4-methoxyphenyl]hexahydro-3H-pyrrolizin-3-one |
| |
Authors: | Sukhorukov Alexey Yu Boyko Yaroslav D Ioffe Sema L Khomutova Yulia A Nelyubina Yulia V Tartakovsky Vladimir A |
| |
Affiliation: | N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991, Leninsky prosp. 47, Moscow, Russian Federation. sukhorukov@server.ioc.ac.ru |
| |
Abstract: | Asymmetric synthesis of GlaxoSmithKline's highly potent phosphodiesterase inhibitor 1 has been accomplished in nine steps and 16% overall yield. The original strategy suggested involves as a key step the silylation of enantiopure six-membered cyclic nitronates 4 obtained by a highly stereoselective [4 + 2]-cycloaddition of an appropriate nitroalkene 5 to trans-1-phenyl-2-(vinyloxy)cyclohexane. Functionalization of the resulting 5,6-dihydro-4H-1,2-oxazine and subsequent stereoselective reduction of 1,2-oxazine ring in intermediate 2 furnished the pyrrolizidinone framework with the recovery of chiral auxiliary alcohol. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|