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Synthesis of 4-cyanophenyl 1,5-dithio-beta-D-glucopyranoside and its 6-deoxy, as well as 6-deoxy-5-ene derivatives as oral antithrombotic agents.
- Source :
-
Carbohydrate research [Carbohydr Res] 1997 Nov 28; Vol. 304 (3-4), pp. 271-80. - Publication Year :
- 1997
-
Abstract
- Condensation of 5-thio-D-glucopyranose pentaacetate with 4-cyanobenzenethiol, in the presence of trimethylsilyl triflate, gave 4-cyanophenyl 2,3,4,6-tetra-O-acetyl-1,5-dithio-alpha-D-glucopyranoside 7 and 3,4,6-tri-O-acetyl-2,5-anhydro-5-thio-D-mannose bis(4-cyanophenyl) dithioacetal 9 in a 2:3 ratio. The latter is probably formed from the 4-cyanophenyl 2,3,4,6-tetra-O-acetyl-1,5-dithio-beta-D-glucopyranoside 6 via a transannular participation of the ring sulfur atom. When 2,3,4,6-tetra-O-acetyl-5-thio-alpha-D-glucopyranosyl bromide was used as donor and the reaction was carried out in the presence of potassium carbonate, 6, 7, 4-cyano-2-(2,3,4,6-tetra-O-acetyl-5-thio-alpha-D-glucopyranosyl)phenyl and 4-cyano-2-(2,3,4,6-tetra-O-acetyl-5-thio-beta-D-glucopyranosyl)phenyl 1,5-dithio-beta-D-glucopyranoside (14 and 16) were formed in a 23:4:2:1 ratio. The mechanism of formation of 14 and 16 is discussed. Condensation of 2,3,4,-tri-O-acetyl-6-deoxy-5-thio-alpha-D-glucopyranosyl bromide with 4-cyanobenzenethiol in the presence of potassium carbonate gave 4-cyanophenyl 2,3,4-tri-acetyl-6-deoxy-1,5-dithio-alpha- and beta-D-glucopyranoside (29 and 30) as well as 4-cyano-2-(2,3,4-tri-O-acetyl-6-deoxy-5-thio-alpha-D-glucopyranosyl)phen yl 2,3,4-tri-O-acetyl-6-deoxy-1,5-dithio-beta-D-glucopyranoside in a ratio of approximately 1:8:1. Compound 30 could be obtained in a higher overall yield using 2 as starting material and converting it via its 4-cyanophenyl 2,3,4-tri-O-acetyl-6-O-methanesulfonyl-1,5-dithio-beta-D-glucopyranoside derivative into the 4-cyanophenyl 2,3,4-tri-O-acetyl-6-deoxy-6-iodo-1,5-dithio-beta-D-glucopyranoside 33 which gave 30 on reduction with sodium borohydride-nickel(II) chloride. Treatment of 33 with silver acetate gave 4-cyanophenyl 2,3,4-tri-O-acetyl-6-deoxy-1,5-dithio-beta-D-xylo-hex-5-enopyranoside 35. The compounds obtained on deacetylation of 6, 9, 14, 30 and 35 showed a stronger oral antithrombotic effect in rats as compared to beciparcil, used as reference.
- Subjects :
- Administration, Oral
Animals
Carbohydrate Conformation
Fibrinolytic Agents administration & dosage
Fibrinolytic Agents pharmacology
Indicators and Reagents
Nuclear Magnetic Resonance, Biomolecular
Optical Rotation
Rats
Thioglucosides administration & dosage
Thioglucosides pharmacology
Fibrinolytic Agents chemical synthesis
Thioglucosides chemical synthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0008-6215
- Volume :
- 304
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Carbohydrate research
- Publication Type :
- Academic Journal
- Accession number :
- 9468629
- Full Text :
- https://doi.org/10.1016/s0008-6215(97)10041-6