Selective deformylation of an α,β-unsaturated sugar aldehyde in a very short synthesis of 3'-azido-3'-deoxythimidine (AZT) and its stereoisomers

Article abstract of DOI:10.1055/s-1991-26490

(2E,4S)-5-Acetoxy-4-formyloxy-2-pentenal (2) prepared in one step from tri-O-acetyl-d-glucal was selectively deformylated to give the α,β-unsaturated aldehyde 3 with an unprotected hydroxy group at C-4. Michael-type addition reaction of hydrazoic acid to 3 followed by acylation at C-1 gave a 1:1 mixture of the erythro- and threo-isomers of 5-O-acetyl-3-azido-1-O-(4-biphenylcarbonyl)-2,3-dideoxypentofuranoses 4 and 5. They were used as substrates for nucleoside coupling with silylated thymine to give all four D-isomers of 3'-azido-3'-deoxythymidine 6-9.