Synthesis and HIV inhibition activity of 2',3'-dideoxy-3'-C-hydroxymethyl nucleosides

A series if 2',3'-dideoxy-3'-C-hydroxymethyl purine nucleosides were prepared based on the photochemical ring expansion of a chiral cyclobutanone precursor, (2S)-trans-2,3-bis[(benzoyloxy)methyl]cyclobutanone, in the presence of a 6-substituted purine. Both alpha- and beta-anomers are produced in this transformation. Deprotection was effected by reaction of the photoadducts with saturated methanolic ammonia. Nine purine nucleosides were tested for their inhibitory effect of HIV IIIB virus on H9 cells. The 6-hexyloxy and adenine derivatives 4e,c, respectively, appeared to be most effective at inhibiting viral reproduction with 4c comparable in activity to ddI and AZT.