SYNTHESIS AND EVALUATION OF ANTI-HIV-1 AND ANTITUMOR-ACTIVITY OF 2',3'-DIDEHYDRO-2',3'-DIDEOXY-3-DEAZAADENOSINE, 2',3'-DIDEOXY-3-DEAZAADENOSINE AND SOME 2',3'-DIDEOXY-3-DEAZAADENOSINE 5'-DIALKYL PHOSPHATES

The 4-amino-1-(2,3-dideoxy-beta-D-glycero-pent-2-enofuranosyl)-1H-imidazo[4,5-c]pyridine (1) and 4-amino-1-(2,3-dideoxy-beta-D-glycero-pentofuranosyl)-1H-imidazo[4,5-c]pyridine (2), 3-deaza analogues of the anti-HIV agents 2',3'-didehydro-2',3'-dideoxyadenosine (d4A) and 2',3'-dideoxyadenosine (ddA), have been synthesized. The reaction of 3-deazaadenosine (3) with 2-acetoxyisobutyryl bromide yielded a mixture of cis and trans 2',3'-halo acetates which was converted into olefinic nucleoside (1) on treatment with a Zn/Cu couple and then with methanolic ammonia. The 2',3'-dideoxy-3-deazaadenosine (2) was obtained by catalytic reduction of 1. A number of phosphate triester derivatives of 2 have also been prepared. The diethyl-, dipropyl- and dibutyl-phosphates 7a-c and 3-deazaadenosine have shown anti-HIV activity at non-cytotoxic doses. Compounds 7a-c have also shown significant cytostatic activity against murine colon adenocarcinoma cells.