秋水仙碱及其天然类似物(-)-N-乙酰秋水酚甲醚的不对称合成

Asymmetric Synthesis of(-)-Colchicine and Its Natural Analog(-)-N-Acetylcolchicine Methyl Ether

采用相对简单的不对称合成方法,完成了秋水仙碱及其天然类似物(-)-N-乙酰秋水酚甲醚(NCME)的形式全合成.首先经简单醛、酮的Aldol缩合完成碳骨架的构筑,然后经手性亚磺酰胺诱导的不对称还原胺化反应,廉价、高效地合成了手性胺中间体;再经过高价碘试剂的氧化关环,构筑该类生物碱的三元环结构.本策略为该类生物碱的简便、快速合成提供了有效方法.

(-)-Colchicine and its natural analogue(-)-N-acetylcolchinol methyl ether have been synthesized in a comparatively conciser asymmetric synthetic approach.Firstly,the carbon framework was constructed by Aldol condensation of simple aldehydes and ketones,and then the chiral amine intermediates were synthesized economically and efficiently through asymmetric reductive amination with chiral tert-butanesulfinamide.The 3-rings skeleton of colchicine and related alkaloids was then constructed by oxidation with hypervalent iodine reagent.Our strategy provides an efficient method for the convenient and economical synthesis of these alkaloids.