Novel Variants of the Zwitterionic Claisen Rearrangement and the Total Synthesis of Erythronolide B

claisen;erythromycin;erythronolide;macrolide antibiotics;sigmatropic rearrangement;tandem;total synthesis

Dong, Vy Maria ; MacMillan, David W. C.

University:California Institute of Technology

Department:Chemistry and Chemical Engineering

关键词: claisen;    erythromycin;    erythronolide;    macrolide antibiotics;    sigmatropic rearrangement;    tandem;    total synthesis;   

Others  :  https://thesis.library.caltech.edu/754/7/thesis_vmd.pdf

美国|英语

来源: Caltech THESIS

【 摘 要 】

This dissertation describes the development of three novel variants of the zwitterionic Claisen rearrangement.Initial studies demonstrate an efficient and diastereoselective ketene-Claisen rearrangement catalyzed by metal salts.This process involves the condensation of ketenes and allylic amines to form zwitterionic enolates which undergo [3,3]-sigmatropic rearrangements to afford alpha,beta-disubstituted-gamma,delta-unsaturated amides.The scope of this chemistry is further expanded through the development of a Lewis acid-catalyzed acyl-Claisen rearrangement which employs acid chlorides as ketene surrogates.Based on these studies, a new tandem acyl-Claisen rearrangement for the construction of structurally complex 1,7-dioxo-acyclic architectures is achieved.The versatility of this tandem transformation for macrolide antibiotic synthesis is demonstrated through a concise total synthesis of erythronolide B, in 24 linear steps.