A Ca2+-mobilising carbohydrate-based polyphosphate: synthesis of 2-hydroxyethyl α-d-glucopyranoside 2′,3,4-trisphosphate

Two routes to a glucose-based mimic of the second messenger 1d-myo-inositol 1,4,5-trisphosphate related to adenophostin A are described. Fischer glycosidation of d-glucose with allyl alcohol in the presence of a strong cation-exchange resin gave a 7:3 α:β-anomeric mixture of allyl glucopyranosides (5ab) from which the pure α anomer 5a was isolated by crystallisation. Treatment of 5ab with 1.05 equiv of dibutyltin oxide followed by 2.1 equiv of benzoyl chloride gave allyl 2,6-di-O-benzoyl-α-d-glucopyranoside, which was converted in 3 steps into allyl 2,6-di-O-benzyl-3,4-O-isopropylidene-α-d-glucopyranoside (4). Alternatively, treatment of 5a with 2.5 equiv of dibutyltin oxide followed by benzyl bromide gave allyl 2,6-di-O-benzyl-α-d-glucopyranoside (9) which was also converted into 4. Compound 4 was elaborated to the phosphorylation precursor 2-hydroxyethyl 2,6-di-O-benzyl-α-d-glucopyranoside (12) in a convenient one-pot reaction, and 12 was phosphorylated and deblocked to afford 2-hydroxyethyl α-d-glucopyranoside 2′,3,4-trisphosphate. The 2,6-di-O-benzyl derivative 9 was converted in high yield into 2,6-di-O-benzyl-3,4-di-O-(p-methoxybenzyl)-d-glucopyranose, a useful intermediate for the synthesis of adenophostin A and related compounds.