2′, 3′‐Dideoxy‐3′‐fluorotubercidin and Related Dideoxyribonucleosides:. Synthesis via a 2′‐deoxy‐3′‐oxoribofuranoside intermediate and conformation studies

An efficient synthesis of the unknown 2′‐deoxy‐D‐ threo ‐tubercidin ( 1b ) and 2′, 3′‐dideoxy‐3′‐fluorotubercidin ( 2 ) as well as of the related nucleosides 9a, b and 10b is described. Reaction of 4‐chloro‐7‐(2‐deoxy‐β‐D‐ erythro ‐pentofuranosyl)‐7 H ‐pyrrolo[2,3‐ d ]pyrimidine ( 5 ) with ( tert ‐butyl)diphenylsilyl chloride yielded 6 which gave the 3′‐keto nucleoside 7 upon oxidation at C(3′). Stereoselective NaBH 4 reduction (→ 8 ) followed by deprotection with Bu 4 NF(→ 9a )and nucleophilic displacement at C(6) afforded 1b as well as 7‐deaza‐2′‐deoxy‐D‐ threo ‐inosine ( 9b ). Mesylation of 4‐chloro‐7‐{2‐deoxy‐5‐ O ‐[( tert ‐butyl)diphenylsilyl]‐β‐D‐ threo ‐pentofuranosyl}‐7 H ‐pyrrolo[2,3‐ d ]‐pyrimidine ( 8 ), treatment with Bu 4 NF (→ 12a ) and 4‐halogene displacement gave 2′, 3′‐didehydro‐2′, 3′‐dideoxy‐tubercidin ( 3 ) as well as 2′, 3′‐didehydro‐2′, 3′‐dideoxy‐7‐deazainosne ( 12c ). On the other hand, 2′, 3′‐dideoxy‐3′‐fluorotubercidin ( 2 ) resulted from 8 by treatment with diethylamino sulfurtrifluoride (→ 10a ), subsequent 5′‐de‐protection with Bu 4 NF (→ 10b ), and Cl/NH 2 displacement. 1 H‐NOE difference spectroscopy in combination with force‐field calculations on the sugar‐modified tubercidin derivatives 1b , 2 , and 3 revealed a transition of the sugar puckering from the 3′ T 2′ conformation for 1b via a planar furanose ring for 3 to the usual 2′ T 3′ conformation for 2.