The synthesis of uridine diphosphate N-acetylhexosamines and uridine 5′-(2-acetamido-2-deoxy-α-D-mannopyranosyluronic acid diphosphate)

Abstract

2-Methyl-(2-acetamido-3,4,6-tri-O-acetyl-l,2-dideoxy-β-D-mannopyrano)-[2,1-d]-2-oxazoline was efficiently converted into 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-mannopyranosyl phosphate, by treatment with dibenzyl phosphate, followed by catalytic hydrogenolysis of the benzyl groups. Similarly, 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-glucopyranosyl phosphate and -galactopyranosyl phosphate were synthesized from the respective peracetyl oxazolines. In each case, the procedures for preparing the oxazoline, and conversion into the glycosyl phosphate, were modified to give high yields of pure products. 2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-mannopyranosyl phosphate was coupled with 2′,3′-di-O-acetyluridine 5′-monophosphate by a modification of the mixed anhydride procedure, to give 2',3'-di-O-acetyluridine 5′-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-α-D-mannopyranosyl diphosphate), which was readily purified by preparative tic and O-deacetylated to give "uridine diphosphate N-acetylmannosamine" in high yield. Similarly, uridine 5′-(2-acetamido-2-deoxy-α-D-glucopyranosyl- and -galactopyranosyl diphosphates) were synthesized by rapid, efficient procedures, not involving ion-exchange chromatography. Uridine 5′-(2-acetamido-2-deoxy-α-D-mannopyranosyl diphosphate) was converted into uridine 5′-(2-acetamido-2-deoxy-α-D-mannopyranosyluronic acid diphosphate), required for biosynthetic studies, without the preparation of a special platinum catalyst. All the synthetic uridine diphosphate sugars were characterized by optical rotation, 1H nmr spectrum, and elemental analysis.