The Synthesis of gem-Halonitro Sugars and Their Conversion into Epoxynitro Sugars

Abstract

Halogenation of methyl 4,6-O-benzylidene-3-deoxy-3-nitrohexopyranosides having the α-D-talo, β-D-galacto, and α-D-galacto configurations, and of the 2,3-dideoxy-3-nitro β-D-lyxo and α-D-lyxo analogs, smoothly furnished 3-halo-3-deoxy-3-nitro derivatives. The glycosides were chlorinated in methanolic solution with aqueous sodium hypochlorite, and similarly brominated with either bromine in the presence of alkali or N-bromoacetamide in the presence of sodium acetate. The analogous nitro glycosides having the β-D-arabino, β-D-manno, α-D-manno, and β-D-gluco configurations and also the 2-acetates of the last three compounds were brominated likewise whereas the α-D-gluco isomer and its 2-acetate were resistant under the conditions examined. The preferred C-3 configuration in the halonitro products appeared to be that which has an equatorial nitro group and an axial halogen atom in the normal pyranose chair conformation (4C1). In most instances the halogenation was found to be highly stereoselective in that sense although in some cases the inverse C-3 epimer was formed in a minor proportion. Base treatment of some of the halohydrins led to 2,3-anhydro-3-nitro glycosides. Such epoxide formation may be associated with epimerization at C-2 and -3, for which a mechanism involving a retrograde Henry reaction is postulated.