Synthesis of 2-deoxy-α- and -β-D-arabino-hexopyranosyl phosphonic acids and related compounds; analogues of early intermediates in the shikimate pathway

Abstract

Treatment of 1-O-acetyl-3,4,6-tri-O-benzyl-2-deoxy-D-arabino-hexopyranose 18 with trimethyl phosphite in the presence of trimethylsilyl triflate gave a separable mixture of dimethyl (3,4,6-tri-O-benzyl-α-D-arabino-hexopyranosyl)phosphonate 19 (35%) and the β-anomer 20 (60%). The diethyl analogue of compound 20 could be prepared stereoselectively from tributyl (3,4,6-tri-O-benzyl-2-deoxy-β-D-arabino-hexopyranosyl)stannane 21 and diethyl chlorophosphate.

Reaction of 1,3,4,6-tetra-O-acetyl-2-deoxy-D-arabino-hexopyranose 23 with trimethyl phosphite and trimethylsilyl triflate gave dimethyl (3,4,6-tri-O-acetyl-2-deoxy-α-D-arabino-hexopyranosyl)phosphonate 25 and the β-anomer 27 with some α-selectivity. Deprotection of compounds 25 and 27 gave the phosphonic acids 11 and 12 respectively. The esters 25 and 27 could be converted into methyl 3,4,6-tri-O-acetyl-2-deoxy-1-(dimethoxyphosphoryl)-β-D-arabino-hexopyranoside 31 by free-radical bromination followed by methanolysis, and diethyl [3,4,6-tri-O-(tert-butyldiphenylsilyl)-2-deoxy-D-arabino-hex-1-enopyranosyl]phosphonate 33 was prepared by interaction of the 1-lithioglucal with diethyl chlorophosphate.

Metallation of stannane 21 and reaction with methyl chloroformate gave methyl 2,6-anhydro-4,5,7-tri-O-benzyl-3-deoxy-D-gluco-heptonate 35 which could be alkylated with tert-butyl bromoacetate to give, after deprotection, 3,7-anhydro-3-carboxy-2,4-dideoxy-D-gluco-octonic acid 14.