Synthesis of unusual N-acylated aminosugar fragments of Mycobacterium marinum lipooligosaccharide IV.

Abstract

A convergent strategy was developed for the stereoselective synthesis of four unusual N-acylated monosaccharides (5-8), which are fragments of lipooligosaccharide IV (LOS-IV) from Mycobacterium marinum. A critical substrate-controlled asymmetric cyclization of an amino acid derived oxazolidine provided a key lactam intermediate 11, which was successfully converted to targets 5-7. The key step in the synthesis of 8 was a one-pot cascade oxidation-cyclization-oxidation reaction of a Boc-protected amino alcohol, prepared from 3-butynol, which led to the formation of lactam 15. The five-membered ring lactam intermediates in these synthetic routes were sensitive to elimination side reactions, but careful manipulation of the reaction sequence allowed for the stereoselective synthesis of the targets. This work represents the first synthesis of these unusual motifs, which have been shown to be essential to the bioactivity of LOS-IV.