Synthesis of glucose phosphate derivatives by the phosphite triester method

Abstract

Synthesis of sugar phosphate derivatives by means of phosphite triester method is described. Seven glucose phosphotriester derivatives have been prepared, i.e. dimethyl, methyl n-propyl, and methyl isopropyl (1, 2:5, 6-di-O-isopropylidene-α-D-glucofuranose-3-) phosphate (5, 7 and 8); methyl bis-(1, 2:5, 6-di-O-isopropylidene-α-D-glucofuranose-3-) phosphate (6); methyl bis-(1, 2, 3, 4-tetra-O-acetyl-β-D-glucopyranose-6-) phosphate (9); methyl bis-(1, 2-O-isopropylidene-3,5-O-benzylidene-α-D-glucofuranose-6-) phosphate (10); and methyl (1, 2, 5, 6-di-O-iso-propylidene-α-D-glucofuranose-3-) (1, 2, 3, 4-tetra-O-acetyl-β-D-glucopyranose-6-) [phosphate (11). The results of the displacement of second chlorine atom of the reagent by different alcohols showed that methanol, n-propanol, isopropanol and as well as the glucose derivatives reacted normally to give the expected phosphite esters which yield the expected phosphate products after oxidation, but not the t-butanol. Removal of methyl group from a phosphotriester linkage can be easily achieved by the action of t-butyl amine and thus, t-butyl ammonium bis-(1, 2:5, 6-di-O-isopropylidene-α-D-glucofuranose-3-) phosphate t-butyl amine salt (12) has been obtained from its parent phosphotriester in nearly quantitative yield. The mass spectra data of di-O-isopropylideneglucose phosphate reveals that the cleavage of these compounds follows a general pattern and can be used for their characterization.