SYNTHESIS OF 7-HALOGENATED 8-AZA-7-DEAZA-2'-DEOXYGUANOSINES AND RELATED PYRAZOLO[3,4-D]PYRIMIDINE 2'-DEOXYRIBONUCLEOSIDES

The synthesis of 7-bromo and 7-iodo derivatives of 8-aza-7-deaza-2'-de oxyguanosine (2, 3) as well as the halogenated 4-alkoxy derivatives 4a -c and 5a-c is described. Glycosylation of the halogenated pyrazolo[3, 4-d]pyrimidine anions of 7a-c or 8a-c with ,5-di-O-(p-toluoyl)-alpha-D -erythro-pentofuranosyl chloride (9) yields regioisomeric glycosylatio n products, the N(1)-isomers 10a-c and 11a-c as well as the N(2)-compo unds 12a-c. The latter isomers lose their halogen during the glycosyla tion in the presence of non-anhydrous KOH. Anhydrous conditions (NaH) furnished 10c, 11c together with the halogenated N(2)-isomers 13a,b. C ompounds 10a-c, and 11a-c were deprotected and converted to the 4-alko xy nucleosides 4a-c and 5a-c. The N(1)-nucleosides 4c and 5c were hydr olyzed to give the 7-bromo or 7-iodo derivatives of 8-aza-7-deaza-2'-d eoxyguanosines 2 and 3. Different from regular 2'-deoxyribonucleosides the sugar moiety of pyrazolo[3,4-d]pyrimidine 2'-deoxyribonucleosides shows a preferred N-type pucker (T-3(2)) in solution a conformation w hich is also detected in the solid state.