Assessment of synthetic methods for the preparation of N-beta-d-glucopyranosyl-N'-substituted ureas, -thioureas and related compounds

Preparation of O-peracetylated N-beta-d-glucopyranosyl-N'-acyl urea derivatives resulted in the formation of anomeric mixtures under the following conditions: acylation of O-peracetylated beta-d-glucopyranosyl urea by acyl chlorides in the presence of ZnCl(2) in refluxing CHCl(3); addition of O-peracetylated beta-d-glucopyranosylamine to acyl isocyanates in acetonitrile at rt; addition of carboxamides to in situ prepared O-peracetylated beta-d-glucopyranosyl isocyanate in refluxing toluene. Deprotection of O-peracetylated N-beta-d-glucopyranosyl-N'-acyl ureas either under base (NaOMe in MeOH at or below rt) or under acid (KHSO(4) or AcCl in MeOH at rt) catalyzed transesterification conditions resulted in unavoidable partial cleavage of the N'-acyl moieties. Reaction of beta-d-glucopyranosylammonium carbamate with an isocyanate, isothiocyanate or isoselenocyanate in dry pyridine at rt appears as a general method for the preparation of the corresponding beta-d-glucopyranosyl ureas, -thio- and -selenoureas, respectively, inclusive N'-acyl derivatives.