(8R,8aS)-及(8R,8aR)-8-羟基-5-吲哚里西啶酮的不对称合成:两个有用的羟基吲哚里西啶合成砌块

Abstract

以3-苄氧基哌啶-2,6-二酮衍生物20为起始原料,分别合成了两类新的合成砌块(8r,8AS)-及(8r,8Ar)-8-羟基-5-吲哚里西啶酮19A/19b和15A/15b.19A/19b的合成是基于反式非对映立体选择性还原烷基化反应(dr=93:7),接着经4步转化而成;而化合物15A/15b的制备则以双烯29的rCM反应为关键步骤,再经顺式立体选择性催化氢化(dr=91:9)反应完成.此外,还原化合物15A得到了(8r,8Ar)-8-羟基-5-吲哚里西啶18.

Starting from the oxygenated piperidine building block 20,two synthetic approaches to new building blocks(8R,8aS) -and(8R,8aR) -8-hydroxy-5-indolizidinones 19a/19b and 15a/15b have been developed,respectively.The first one is based on the trans-diastereoselective reductive alkylation(dr=93:7) ,followed by a four-step procedure;and the second one called for the RCM reaction on the N,O-acetal derived from a vinylation,which was followed by a pyrrole formation,and a stereocontrolled cis-selective(dr=91:9) catalytic hydrogenation.Reduction of the diastereomer 15a produced(8R,8aR) -8-indolizidinol(18).