2’-Deoxypuromycin: Synthesis and Antiviral Evaluation

A new synthesis of 2’-deoxypuromycin (18) as well as its α-anomer 17 is described. Reaction of 1,5-di-O-acetyl-2,3-dideoxy-3-phthalimido-β-D-erythro-pentofuranose (3) with silylated 6-dimethylaminopurine using trimethylsilyl trifluoromethanesulfonate as catalyst afforded the α and β nucleosides 7 and 12 in 15 and 25% yield, respectively. After deblocking of both amino and hydroxy groups with methylamine in ethanol, the nucleosides were condensed with Fmoc-4-O-methyl-L-tyrosine and subsequently deprotected to give the target compounds 17 and 18. Compound 3 is converted into its glycosyl bromide 4 in quantitative yield on treatment with trimethylsilyl bromide, and reacted with the sodium salt of 6-dimethylaminopurine to give the corresponding protected N-7 and N-9 α glycosyl nucleosides 7 and 8 in 34 and 39% yield, respectively. The 2’-deoxypuromycin is inactive against HIV-1 in MT-4 cells.

2’-deoxypuromycin - nucleoside synthesis - adenosine - 3’-amino-2’,3’-deoxy-N ⁶ ,N ⁶-dimethyl - nucleosides - 2’-deoxy,3’-phthalimido - HIV-1