Synthesis of 7-alkynylated 8-aza-7-deaza-2′-deoxyadenosines via the Pd-catalysed cross-coupling reaction

Abstract

The synthesis of 7-alkynylated 8-aza-7-deazaadenine (pyrazolo[3,4-d]pyrimidine) 2′-deoxyribonucleosides is described. Nucleobase anion-glycosylation of 8-aza-7-deaza-7-iodo-6-methoxypurine (15) with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranosyl chloride (16) furnishes the 8-aza-7-deaza-7-iodo-6-methoxypurine N¹-β-D-2′-deoxyribonucleoside 17a as the main product (38% yield). After detoluoylation of products 17a and 17b²⁷ (→ 19a,b) and amination the 7-bromo and the 7-iodo derivatives of 8-aza-7-deaza-2′-deoxyadenosine (compounds 2b,c) were obtained. Compound 2b served as the starting material for a series of 7-alkynyl- or 7-alkenyl-8-aza-7-deazaadenine 2′-deoxynucleosides 3–13 by employing the Pd⁰/Cu^I-catalysed cross-coupling reaction. The 7-halogenated or 7-alkynylated nucleosides show a more stable glycosylic bond than does 8-aza-7-deaza-2′-deoxyadenosine (2a).