The first synthesis of N,O-protected β 2,2,3,3-isoserines bearing two adjacent quaternary stereogenic centers and their corresponding β-lactams

Abstract

The reaction of chiral (2 S)-enolates of dioxolan-4-ones, derived from lactic and mandelic acids, with ( S R )- tert-butyl sulfinyl ketimines, derived from butan-2-one, pentan-2-one, and decan-2-one, afforded conformationally restrained β 2,2,3,3-isoserines bearing two adjacent quaternary stereogenic centers in the form of N-sulfinyl protected 1′-amino-dioxolan-4-ones. The selective acid-induced removal of the sulfinyl protecting group provided the corresponding 1′-aminodioxolanones, whose base-induced cyclization afforded the corresponding chiral tetra-substituted 3-hydroxy-β-lactams. The synthesis of a dipeptide by reaction coupling between the 1′-aminodioxolanone (2 S,5 R,1′ R)- 19 and N, N-dimethylglycine was successfully achieved.