Model studies towards the synthesis of 4′-azaerythrofuranosyladenines as analogues of the antiviral drug 2′,3′-dideoxyadenosine (ddA)1

Abstract

The [3 + 2] dipolar cycloaddition of nitrones to N-9-vinyladenine provides a regioselective and stereoselective method for the obtainment of 4′-aza-analogues of 2′,3′-dideoxyadenosine. The latter may act as antiviral agents by analogy with the behaviour in vitro of the corresponding thymine analogue. The formation of the unsubstituted isoxazolidino derivative requires the protection of the 6-NH₂ function of the dipolarophile, which is not necessary when preformed nitrones are used. The obtainment of a specific enantiomer has been exploited by enzyme-catalysed hydrolysis of an ester function introduced into the isoxazolidino nucleus.