Nucleoside Analogues from Branched-Chain Pyranosides

Abstract

Reaction of (pyranosid-3-yl)ethanal 2 with ethynylmagnesium bromide or lithium phenylacetylide in THF afforded (2R,S)-1-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-yl)but-3-yn-2-ols 3a and 3b, respectively. Oxidation of 3a and 3b yielded the 1-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-yl)but-3-yn-2-ones 4a and 4b, which upon treatment with hydrazine and hydrazine derivatives formed the 3-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-ylmethyl)pyrazoles 5a–5d. Compounds 4a and 4b also underwent reaction with amidinium and guanidinium salts under basic conditions to furnish the 4-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-ylmethyl)pyrimidines 8a–8f. Furthermore, treatment of 4a and 4b with 2-aminobenzimidazole yielded the 2-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-d-altropyranosid-3-ylmethyl)benzo[4,5]imidazo[1,2-a]pyrimidines 11a and 11b. Deprotection of 5a and 8b in two steps afforded 3(5)-(methyl 3-deoxy-α-d-altropyranosid-3-ylmethyl)-1H(2H)-pyrazole 7 and 4-(methyl 3-deoxy-α-d-altropyranosid-3-ylmethyl)-2-phenylpyrimidine 10, respectively. Compound 11a was treated with AcOH/H2O to furnish 2-(methyl 2-O-benzyl-3-deoxy-α-d-altropyranosid-3-ylmethyl)benzo-[4,5]imidazo[1,2-a]pyrimidine 13.