Free-radical synthesis of 3-(2-cyanoethyl)- and 3-(2-methoxycarbonylethyl)-2,3-dideoxy-alpha-D-erythro-pentofu ranoside and their application in the synthesis of potential antiviral nucleosides.
Free-radical reaction of different carbohydrate educts 2, 5, and 7 with acrylonitrile in the presence of tributyltin hydride and a radical initiator (AIBN) gave the methyl 3-(2-cyanoethyl)-2,3-dideoxypentofuranosides 3a and 6. Similar reaction of 2 with methyl acrylate gave 3-(2-methoxycarbonylethyl)-2,3-dideoxypentofuranose 3b. Nucleoside coupling of 3a with silylated uracil gave an anomeric mixture of beta- and alpha-nucleoside 8 and 9 which were deprotected to give 10 and 11, respectively. Similar reaction of 3b with silylated N4-isobutyrylcytosine gave 12 and 13 which were deprotected to give the final nucleosides 16 and 17, respectively. None of the compounds 10a, 11, 14-17 showed significant activity against HIV.
Lau
J
J
Department of Chemistry, Odense University, Denmark.
Walczak
K
K
Pupek
K
K
Buch
C
C
Nielsen
C M
CM
Pedersen
E B
EB
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D005609:Free Radicals; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology; D006678:HIV / Q000187:drug effects; D008759:Methylglycosides / Q000138:chemical synthesis* / Q000494:pharmacology
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D005609:Free Radicals; D005663:Furans; D008759:Methylglycosides