Synthesis of 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (FddA) via a purine 3'-deoxynucleoside.
A synthesis of 9-(2,3-dideoxy-2-fluoro-beta-D-threo-pentofuranosyl)adenine (1, FddA) via a 6-chloro-9-(3-deoxy-beta-D-erythro-pentofuranosyl)-9H-purine (9), which was readily obtained from inosine (5), is described. Fluorination at the C2'-beta position of the purine 3'-deoxynucleoside with diethylaminosulfur trifluoride was improved by the introduction of a 6-chloro group and proceeded in moderate yield. Purine 3'-deoxynucleoside derivatives were also subjected to nucleophilic reactions with triethylamine trihydrofluoride and gave the desired fluorinated nucleoside in good yield. The safety and yield of the fluorination process were greatly improved by the use of triethylamine trihydrofluoride. The influence of the sugar ring conformation and 6-chloro group on the rate of the nucleophilic reaction against elimination are also discussed.
Takamatsu
S
S
AminoScience Laboratories, Ajinomoto Co., Inc. 1-1, Suzuki-cho, Kawasaki-ku, Kawasaki, Kanagawa 210-8681, Japan.
Maruyama
T
T
Katayama
S
S
Hirose
N
N
Naito
M
M
Izawa
K
K
D019380:Anti-HIV Agents / Q000138:chemical synthesis*; D003839:Deoxyadenosines / Q000737:chemistry; D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D008968:Molecular Conformation
D019380:Anti-HIV Agents; D003839:Deoxyadenosines; C073072:lodenosine; D016048:Dideoxyadenosine