The synthesis of phosphorylated disaccharide components of the extracellular phosphomannan of Pichia (Hansenula) holstii NRRL Y-2448.
Methods for the stereoselective synthesis of alpha-(1-->2)- and alpha-(1-->3)-linked 6(II)-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-alpha-D-mannopyranosyl)-D-mannopyranose and methyl 3-O-(6-O-phospho-alpha-D-mannopyranosyl)-alpha-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.
Fairweather
Jon K
JK
Drug Design Group, Progen Industries Ltd, 2806 Ipswich Road, Darra, Queensland 4076, Australia.
Karoli
Tomislav
T
Ferro
Vito
V
D020533:Angiogenesis Inhibitors / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry; D004187:Disaccharides / Q000138:chemical synthesis*; D008351:Mannans / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry; D010843:Pichia / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013403:Sugar Phosphates / Q000138:chemical synthesis*
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D004187:Disaccharides; D008351:Mannans; D009844:Oligosaccharides; D013403:Sugar Phosphates; C120158:phosphomannopentaose sulfate; C005437:phosphomannan