Tetramate derivatives by chemoselective Dieckmann ring closure of allo-phenylserines, and their antibacterial activity?

Organic & Biomolecular Chemistry Pub Date: 2023-04-14 DOI: 10.1039/D3OB00376K

Abstract

A general route which provides direct access to substituted bicyclic tetramates, making use of Dieckmann cyclisation of oxazolidine derivatives derived from allo-phenylserines, is reported. Of interest is the high level of diastereoselectivity observed for the N-acylation reaction of oxazolidines and the complete chemoselectivity of their ring closure in the Dieckmann cyclisation. Significantly, the sense of the chemoselectivity is different to earlier reported threo-phenylserine systems, showing the importance of steric bulk around the bicyclic ring system. The derived C7-carboxamidotetramates, but not C7-acyl systems, exhibited potent antibacterial activity against MRSA, with the most active compounds exhibiting well-defined physicochemical and structure–activity properties. This work clearly demonstrates that densely functionalised tetramates are both readily available and may exhibit high levels of antibacterial activity.

Graphical abstract: Tetramate derivatives by chemoselective Dieckmann ring closure of allo-phenylserines, and their antibacterial activity
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