Regioselective synthesis of 3-deazacarbovir and its 3-deaza-adenosine analogues

We herein report the hitherto unknown synthesis of 3-deazacarbovir and its adenosine analogue. The major highlight in the synthesis of adenosine analogs is to use 6-N,N-diboc protected 3-deazapurines 9 and 11 for regioselective Mitsunobu coupling as well as unexplored palladium catalyzed coupling with these substrates. Synthesis of 3-deazacarbovir 1 has been accomplished by the regioselective palladium catalyzed coupling of 6-N,N-diphenylcarbamoyl protected 3-deazaguanine base 18 with dicarbonate 14. All the target nucleosides were screened for anti-HIV-1 activity and none of them have significant activity as well as toxicity up to 100 μM.