シンコナアルカロイドの合成

Abstract

This review summarizes the synthesis of cinchona alkaloids, especially quinine. First, the synthetic efforts done by Rabe, Prelog, and Woodward are briefly mentioned. Described next are the achievements of Uskokovic in 1970 s, who found useful stereoselective transformations, introduced key intermediates, and established transformation of homomeroquinene to quinine, though as a mixture with quinidine. Then, the first completely stereoselective synthesis of quinine published by Stork in 2001 is presented, in which the key step is a stereoselective reduction of the substituted tetrahydropyridine (imine) to the piperidine by using NaBH4. Finally, syntheses of quinine and quinidine published by Jacobsen and by us are presented, both of which feature the stereoselective formation of the epoxide moiety on one of the side chains attached to the piperidine and subsequent intramolecular epoxide ring opening with the piperidine nitrogen, while the construction of the piperidine ring and the stereoselectivities accompanied with are different each other.