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Scalable Protecting-Group-Free Total Synthesis of Resibufogenin and Bufalin

Shao‐Peng Yu, Qiuxin Zhang, Xueqing Zhong, Chao Wang, Wenqing Shi, Jiahua Zhuang, Rui Zhang, Fangjie Jin, Jiange Zhang, Qunfei Zhao, G. Chen, Wenbo Ye, Guo‐Qiang Lin

2024Organic Letters11 citationsDOI

Abstract

A chemoenzymatic synthesis access to resibufogenin and bufalin was developed in seven steps without protecting groups. Starting with androstenedione (AD), an α-OH was introduced directly at C14 by hydroxylase P-450 lun, which was further used as the directing group for hydrogenation to fully control the C17 configuration in the β-orientation after Suzuki cross-coupling. Dehydration of 14α-OH followed by an epoxidation delivered resibufogenin. Simultaneously, bufalin was also obtained via a challenging anaerobic Mukaiyama hydration.

Topics & Concepts

ChemistryBufalinGroup (periodic table)Protecting groupScalabilityCombinatorial chemistryStereochemistryOrganic chemistryDatabaseComputer scienceBiochemistryAlkylApoptosisPhytochemistry and Bioactive CompoundsSteroid Chemistry and BiochemistryPhytochemical Studies and Bioactivities
Scalable Protecting-Group-Free Total Synthesis of Resibufogenin and Bufalin | Litcius