SYNTHESIS AND PROPERTIES OF CONFORMATIONALLY LOCKED 1,3-BISALKYL-7-DEAZAXANTHINE 2'-DEOXY-D-RIBOFURANOSIDES

1,3‐Dimethyl‐7‐deazaxanthine 2′‐deoxyribofuranosides 1a and 6a and their N‐3 isopropyl congeners 1b and 6b have been prepared employing the nucleobase anions 7a or 7b and 2‐deoxy‐3,5‐di‐O‐(p‐toluoyl)‐α‐D‐erythropentofuranosyl chloride (8) upon glycosylation. The reaction was not stereoselective as found in case of other pyrrolo[2,3‐d]pyrimidine nucleosides induced by the bulky N‐3 substituent. Configuration of anomers was established by 1H‐nmr nOe difference spectroscopy. Those data also indicated that the conformation around the N‐glycosylic bond was locked by the bulky N‐3 substituent. Contrary to the purine nucleoside such as wyosine (2a) the hydrolytic stability of the N‐glycosylic bond of the pyrrolo[2,3‐d]pyrimidine nucleosides was increased by N‐3 alkylation. Moreover, it was shown by 15N‐nmr spectroscopy that different to purine nucleosides the aglycon was not protonated in acidic medium. As a result the N‐glycosylic bond hydrolysis did not follow an A‐1 but an A‐2 mechanism. Copyright © 1990 Journal of Heterocyclic Chemistry