Synthesis of the Disaccharide Core of Ezomycin Nucleosides

Abstract

The ezomycins make up a class of complex nucleoside antibiotics that share a common disaccharide core. Herein we present an efficient synthesis of this core from diacetone-d-allose, using a ruthenium-catalyzed asymmetric allylic etherification and a de novo carbohydrate synthesis based on the diastereoselective Henry reaction. Our strategy overcomes several challenges, such as introducing a dense array of functional groups and creating consecutive stereocenters with high selectivity. This approach enables the rapid preparation of disaccharides and paves the way for the total synthesis of ezomycins.

Total Synthesis of Nikkomycin Sz and Nikkomycin Soz

“…As shown in Scheme , the synthesis of compound 2 from 1,2:5,6-di- O -isopropylidene-α- d -allofuranose as the starting material involves a four step process reported by our research group . We initiated the synthesis of 4a by RCM with the second-generation Grubbs catalyst and removal of the acetonide under a variety of acidic conditions, but we obtained a complex mixture, which was tentatively identified as a mixture of 4a , 4b , and 4c .…”