An economic synthesis of 1,2,3,4-tetra- O-acetyl-5-thio- d-xylopyranose and its transformation into 4-substituted-phenyl 1,5-dithio- d-xylopyranosides possessing antithrombotic activity

Abstract

d-Xylose was converted via 1,2- O-isopropylidene- α- d-xylofuranose ( 4) into 3- O-benzoyl-5- S-benzoyl-1,2- O-isopropylidene- α- d-xylofuranose which, after methanolysis, acetylation and subsequent acetolysis afforded 1,2,3,4-tetra- O-acetyl-5-thio- α- d-xylopyranose ( 14) in an overall yield of 36%. Reaction of 4 with thionyl chloride gave a mixture of the diastereomeric cyclic sulfites, the structures of which were established by X-ray crystallography. Their oxidation with sodium periodate afforded the corresponding cyclic sulfate 23. Treatment of 23 with potassium thioacetate gave the potassium salt of 5- S-acetyl-1,2- O-isopropylidene- α- d-xylofuranose 3- O-sulfonic acid ( 26) which, after methanolysis, acetylation and subsequent acetolysis afforded 14 in an overall yield of 56%. Treatment of 4 with sulfuryl chloride gave a mixture containing 5-chloro-3- O-chlorosulfonyl-5-deoxy-1,2- O-isopropylidene- α- d-xylofuranose, 3,7,9,11-tetraoxa-4-thia-10-dimethyl-tricyclo[6,3,0,0 2,6]undecane S-dioxide and 23 in a 2:3:7 ratio. Tetraacetate 14 was converted into the α-1-bromide 18 as well as into the α-1- O-trichloroacetimidate 17. These three compounds were used as donors for the glycosylation with 4-cyanothiophenol, affording the 4-cyanophenyl 2,3,4-tri- O-acetyl-1,5-dithio- α- ( 29) and β- d-xylopyranoside ( 30) in different ratios, depending on the reaction conditions. When donor 18 was used in the presence of potassium carbonate, besides 29 and 30 two aryl C-glycosylated-thioglycosides, i.e. 4-cyano-2-(2,3,4-tri- O-acetyl-5-thio- β- d-xylopyranosyl)phenyl 2,3,4-tri- O-acetyl-1,5-dithio- α- and β- d-xylopyranoside ( 32 and 33) as well as 4-cyano-2-(2,3,4-tri- O-acetyl-5-thio- β- d-xylopyranosyl)phenyl disulfide 34 could be isolated as byproducts. Deacetylation of 30 with sodium methoxide in methanol afforded, besides 4-cyanophenyl 1,5-dithio- β- d-xylopyranoside ( 1), the corresponding 4-[(methoxy)(imino)methyl]phenyl glycoside 2. The 4-cyano group of 1 was converted into the 4-aminothiocarbonyl, the 4-(methylthio)(imino)methyl, the 4-amidino and the 4-(imino)(hydrazino)methyl group. All of these glycosides showed a significant antithrombotic activity on rats.