1-(3-cyano-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine (cyanothymidine): synthesis and antiviral evaluation against human immunodeficiency virus.
1-(3-Cyano-2,3-dideoxy-beta-D-erythro-pentofuranosyl)thymine (cyanothymidine) (3a) has been prepared by an unambiguous route starting from D-xylose. The relative and absolute stereochemistry of 3a and its anomeric isomer 9 have been confirmed by NOE experiments and by X-ray diffraction analysis. In antiviral tests vs HIV 3a was shown to be inactive, a surprising result in view of a preliminary disclosure claiming potent anti-HIV activity. The activity previously assigned to 3a is believed to be due to contamination of that sample with the known antiviral nucleoside analogue 5b.
Greengrass
C W
CW
Pfizer Central Research, Sandwich, Kent, United Kingdom.
Hoople
D W
DW
Street
S D
SD
Hamilton
F
F
Marriott
M S
MS
Bordner
J
J
Dalgleish
A G
AG
Mitsuya
H
H
Broder
S
S
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014961:X-Ray Diffraction
D000998:Antiviral Agents; C058711:cyanothymidine; D013936:Thymidine