Synthesis of 4-cyanophenyl and 4-nitrophenyl 1,5-dithio-D-ribopyranosides as well as their 2-deoxy and 2,3-dideoxy derivatives possessing antithrombotic activity.
1,2,3,4-Tetra-O-acetyl-5-thio-D-ribopyranose as well as its 1-bromide were used as donors in the reaction with 4-cyano- and 4-nitrobenzenethiol, to give the corresponding thioglycosides in different anomeric ratios depending on the reaction conditions. Zemplén deacetylation afforded 4-cyanophenyl as well as 4-nitrophenyl 1,5-dithio-alpha- and beta-D-ribopyranosides, respectively. 1,3,4-Tri-O-acetyl-2-deoxy-5-thio-D-erythro-pentopyranose was synthesized from methyl 2-deoxy-D-erythro-pentofuranoside and was coupled with 4-cyano- and 4-nitrobenzenethiol to give anomeric mixtures from which 4-cyanophenyl as well as 4-nitrophenyl 1,5-dithio-beta-D-erythro-pentopyranosides were isolated after deacetylation. 1,4-Di-O-acetyl-2,3-dideoxy-5-thio-D-glycero-pentopyranose was obtained starting from 1,2,5,6-di-O-isopropylidene-D-mannitol and used as the donor in the glycosylation reaction with 4-cyano- and 4-nitrobenzenethiol. The resulting anomeric mixtures were separated to give, after deacetylation, 4-cyanophenyl as well as 4-nitrophenyl 2,3-dideoxy-1,5-dithio-beta-D-glycero-pentopyranosides. All of these thioglycosides showed significant antithrombotic activity on rats after oral administration.
Bozó
E
E
Institute for Drug Research, Budapest, Hungary.
Boros
S
S
Kuszmann
J
J
D000818:Animals; D000991:Antithrombins / Q000138:chemical synthesis* / Q000494:pharmacology; D003486:Cyanides / Q000138:chemical synthesis; D003855:Deoxyribose / Q000031:analogs & derivatives*; D015394:Molecular Structure; D009596:Nitrophenols / Q000138:chemical synthesis; D051381:Rats; D012266:Ribose / Q000031:analogs & derivatives*; D013865:Thioglycosides / Q000138:chemical synthesis* / Q000494:pharmacology
D000991:Antithrombins; D003486:Cyanides; D009596:Nitrophenols; D013865:Thioglycosides; D003855:Deoxyribose; D012266:Ribose