The synthesis of phosphorylated disaccharide components of the extracellular phosphomannan of Pichia (Hansenula) holstii NRRL Y-2448

Abstract

Methods for the stereoselective synthesis of α-(1→2)- and α-(1→3)-linked 6II-O-phosphomannobiosides were developed. Two strategies were successfully employed: a d-mannosyl acceptor was coupled with a phosphorylated d-mannosyl trichloroacetimidate donor, or alternatively with a differentially 6-O-protected d-mannosyl trichloroacetimidate donor which, after glycosylation, was selectively deprotected and phosphorylated. Two target phosphomannobiosides intended for use in SAR studies of the antiangiogenic drug candidate PI-88, 2-O-(6-O-phospho-α-d-mannopyranosyl)-d-mannopyranose and methyl 3-O-(6-O-phospho-α-d-mannopyranosyl)-α-d-mannopyranoside, were synthesized. The former is a minor component of the side-chain repeating unit of the extracellular phosphomannan of Pichia (Hansenula) holstii NRRL Y-2448, whilst the latter represents a nonreducing end fragment of the phosphomannan.