Regio- and stereoselective synthesis of carbocyclic 2',3'-dideoxy-3'-fluoro nucleosides as potential antiviral agents.
The synthesis and antiviral activity of racemic carbocyclic 2',3'-dideoxy-3'-fluoro nucleosides are reported. Carbocyclic 2',3'-dideoxy-3'-fluoro nucleosides were obtained from the 3-fluoro cyclopentane derivative 4, which was prepared by two methods. The SN2-displacement of the hydroxyl group of (+/-)-(1 beta, 2 alpha, 3 beta, 4 beta)-4-acetamido-2-fluoro-3-hydroxycyclopentylmethyl acetate (1) with Ph3P-I2 followed by tin hydride reduction afforded the 3-fluoroamino alcohol derivative 3. Alternatively, the protected fluoroamino alcohol 3 was prepared by regio- and stereoselective bromo-fluorination of cis-4 beta-acetamidocyclopent-2-enemethyl acetate (5) with hydrogen fluoride-pyridine/N-bromosuccinimide followed by tin hydride reduction to remove the bromine atom. Carbocyclic 2',3'-dideoxy-3'-fluoroguanosine (14) thus obtained was moderately active against herpes simplex virus in vitro.
Nakayama
T
T
Research Center, Asahi Glass Co., Ltd., Yokohama, Japan.
Matsumura
Y
Y
Morizawa
Y
Y
Yasuda
A
A
Uchida
K
K
Takase
H
H
Murakami
Y
Y
Atarashi
S
S
Ikeuchi
T
T
Osada
Y
Y
D000256:Adenoviridae / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000187:drug effects; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D005461:Fluorine / Q000737:chemistry; D006367:HeLa Cells; D014645:Herpesvirus 3, Human / Q000187:drug effects; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects; D018139:Simplexvirus / Q000187:drug effects; D013237:Stereoisomerism; D014709:Vero Cells
D015224:Dideoxynucleosides; D005461:Fluorine