Abstract:
D-Allose and its derivatives play important roles in the field of health care and food nutrition. Pure and well-defined D-allose derivatives can facilitate the elucidation of their structure-activity relationship as an essential step for drug design. The Lattrell-Dax epimerization, refers to the triflate inversion using nitrite reagent, is known as valuable method for the synthesis of rare D-allose derivatives. Here, the influence of protecting group patterns on the transformation efficiency of D-glucose derivatives into synthetically useful D-alloses and D-allosamines
via the Lattrell-Dax epimerization was studied. For C3 epimerization of D-glucose derivatives bearing
O2-acyl group, an anomeric configuration-dependent acyl migration from
O2 to
O3 was found. In addition, a neighbouring group participation effect-mediated S
N1 nucleophilic substitution of the D-glucosamine bearing C2 trichloroacetamido (TCA) group in the Lattrell-Dax epimerization was dependent upon anomeric configuration. Thus, the effect of anomeric configuration on the Lattrell-Dax epimerization of D-glucose suggests that
β-D-glucosides with low steric hindrance at C2 should be better substrates for the synthesis of D-allose derivatives. Significantly, the efficient synthesis of the orthogonally protected D-allose
13 and D-allosamine
18 will serve well for further assembly of complex glycans.