New, Efficient, and High-Yielding Asymmetric Synthesis of (4S,5S)-Cytoxazone

Abstract

A new approach for the asymmetric synthesis of (4S,5S)-cytoxazone 1 in five steps and in 48% overall yield starting from commercially available (R)-epichlorohydrin has been described. The key step include stereoselective 1,2-addition of p-methoxyphenyl magnesium bromide (p-OMePhMgBr) to chiral N-sulfinimine derived from (R)-glyceraldehyde acetonide and (S)-t-BSA, which gave corresponding sulfinamide 2 with high diastereoselectivity. Deprotection of the t-butylsulfonyl group and 1,3-dimethyl acetal in a single step followed by N-Boc protection and subsequent carbonylation yields the targeted (4S,5S)-cytoxazone 1.

GRAPHICAL ABSTRACT

Keywords:

• Chiral N-sulfinimine
• (R)-glyceraldehyde acetonide
• (4R5R)-cytoxazone
• (4S5S)-cytoxazone
• stereoselective 1,2-addition

ACKNOWLEDGMENT

Financial support from the Inogent Laboratories Private Limited (A GVK BIO Company) is gratefully acknowledged.

Notes

^a Yields in parentheses are for recovered starting materials.