Development of CPA-Catalyzed β-Selective Reductive Amination of Cardenolides for the Synthesis and Biological Evaluation of Hydrolytically Stable Analogs.

ABSTRACT: This article describes the development of novel, hydrolytically stable cardiotonic steroid analogs featuring a 3β-amine moiety instead of the commonly found 3β-carbohydrates such as oleandrose. To establish the desired 3β-configuration stereoselectively, a new method based on chiral phosphoric acid-controlled diastereoselective reductive amination with Hantzsch esters was developed. This method utilizes readily available unsubstituted (S)-BINOL-based hydrogen phosphate as the catalyst, enabling the synthesis of 13 different 5β-androsterone and digitoxigenin analogs with up to 36:1 β:α diastereoselectivity. Additionally, this strategy was applied to generate two novel oleandrigenin analogs 15a and 15g in 3 steps from readily available gitoxigenin. The synthetic analogs were subjected to the

SUBMITTER: Perry N 

PROVIDER: S-EPMC12224169 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature