Synthesis of 2'-Deoxytubercidin, 2'-Deoxyadenosine, and Related 2'-Deoxynucleosides via a Novel Direct Stereospecific Sodium Salt Glycosylation Procedure

Article abstract of DOI:10.1021/ja00333a046

A general and stereospecific synthesis has been developed for the direct preparation of 2'-deoxy-β-D-ribofuranosylpurine analogues including 2'-deoxyadenosine derivatives.The reaction of the sodium salt of 4-chloropyrrolo<2,3-d>pyrimidine (4) or 2,4-dichloropyrrolo<2,3-d>pyrimidine (1) with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-α-D-erythro-pentofuranose (25) provided the corresponding N-1,2'-deoxy-β-D-ribofuranosyl blocked derivatives (5 and 2) which, on ammonolysis, gave 2'-deoxytubercidin (6) and 2-chloro-2'-deoxytubercidin (3), respectively, in good yield.This glycosylation also readily proceeds in the presence of a 2-methylthio group.Application of this glycosylation procedure to 4,6-dichloroimidazo<4,5-c>pyridine (10), 6-chloropurine (16), 2,6-dichloropurine (13), and 4-chloropyrazolo<3,4-d>pyrimidine (19) gave 2-chloro-2'-deoxy-3-deazaadenosine (12), 2-'-deoxyadenosine (18), 2-chloro-2'-deoxyadenosine (15), and 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)pyrazolo<3,4-d>pyrimidine (21), respectively.Similarly, glycosylation and ammonolysis of 4,6-dichloro-1H-pyrrolo<3,2-c>pyridine (22) gave 4,6-dichloro-1-(2-deoxy-β-D-erythro-pentofuranosyl)pyrrolo<3,2-c>pyridine (24).This stereospecific attachment of the 2-deoxy-β-D-ribofuranosyl moiety appears to be due to a Walden inversion at the C-1 carbon of 25.