Synthesis of 2′-Deoxyribofuranosides of 8-Aza-7-deazaguanine and Related Pyrazolo[3,4-d]pyrimidines

The N(1)- and N(2)-(2′-deoxyribofuranosides) 1 and 2 , respectively, of 8-aza-7-deazaguanine were prepared via phase-transfer glycosylation in the presence or absence of Bu₄NHSO₄ as catalyst of 6-amino-4-methoxy-lH-pyrazolo[3,4-d]pyrimidine ( 7c ) with 2-deoxy-3,5-di-O-(p-toluoyl)-α-D -erythro-pentofuranosyl chloride ( 10 ). On a similar route, but without catalyst and employing THF as organic phase, the 6-amino-4-chloronucleosides 11b and 12b were synthesized from 7a and converted into the N(1)-and N(2)-substituted 4-thioxo analogues 17a and 18a , respectively. The ratio of N(1)- to N(2)-glycosylation was 2:1 for 7c and 1:1 for 7a , viz. depending on the nucleobase structure. The rate of the H⁺-catalyzed N-glycosyl hydrolysis was strongly decreased for the N(2)-(β-D -2′-deoxyribofuranosides) as compared to the N(1)-compounds. However, the N(1)-nucleoside 1 , which is an isostere of 2′-deoxyguanosine, is sufficiently stable to be employed later in solid-phase oligonucleotide synthesis.