Diversity-oriented synthesis of a cytisine-inspired pyridone library leading to the discovery of novel inhibitors of Bcl-2

[摘要]：Four enantiopure cytisine-inspired scaffolds can be accessed via a versatile pyrrolidine template derived from a stereocontrolled [3+2] azomethine ylide-alkene cycloaddition. Differential ester protection allows for the selective formation of either a bridged bicyclic or tricyclic scaffold via pyridone cyclization. Solid-phase diversification of the pyridone scaffolds yielded a diverse library of 15,000 compounds enabling the discovery of a novel class of Bcl-2 inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

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