Recent advances in the total synthesis of polyhydroxylated alkaloids via chiral oxazines

Abstract

This review summarizes recently established methodologies developed for the enantioselective and diastereoselective synthesis of chiral 1,3-oxazines. These compounds are of interest as advanced synthetic intermediates in the total synthesis of structurally complex and biologically active polyhydroxylated alkaloids such as (+)-1-deoxynojirimycin, (−)-anisomycin, (+)-castanospermine, (+)-casuarine, (−)-conduramine F-1, (−)-sphingofungin B, Neu5Ac methyl ester, and other natural products. The devised synthetic approach aims to offer a direct, efficient, and adaptable method for obtaining both pure enantiomers and pure diastereomers. It revolves around utilizing chiral building blocks like syn,syn-, syn,syn,anti-, syn,anti-, syn,anti,syn-, anti,syn-, anti,syn,syn-, and anti,syn,anti-oxazines. By integrating oxazine chemistry with established and innovative transformations, this approach enabled the synthesis of 30 polyhydroxylated amines across various studies conducted between 2007 and 2022.