ORALLY-ACTIVE ANTITHROMBOTIC THIOGLYCOSIDES - PART V - 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

D-Xylose was converted via 1,2-O-isopropylidene-alpha-D-xylofuranose ( 4) into -benzoyl-1,2-O-isopropylidene-alpha-D-xylofuranose which, afte r acetylation and subsequent acetolysis afforded 1,2,3,4-tetra-O-acety l-5-thio-alpha-D-xylopyranose (14) in an overall yield of 36%. Reactio n of 4 with thionyl chloride gave a mixture of the diastereomeric cycl ic sulfites, the structures of which were established by X-ray crystal lography. Their oxidation with sodium periodate afforded the correspon ding cyclic sulfate 23. Treatment of 23 with potassium thioacetate gav e the potassium salt of S-acetyl-1,2-O-isopropylidene-alpha-D-xylofura nose 3-O-sulfonic acid (26) which, after methanolysis, acetylation and subsequent acetolysis afforded 14 in an overall yield of 56%. Treatme nt of 4 with sulfuryl chloride gave a mixture containing 5-chloro-3-O- chlorosulfonyl-5-deoxy- 1,2-O-isopropylidene-alpha-D-xylofuranose, -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 alpha-1-bromide 18 as well as into the alpha-1-O-trichloroacetimidate 17. These three co mpounds were used as donors for the glycosylation with 4-cyanothiophen ol, affording the 4-cyanophenyl 2,3,4-tri-O-acetyl-1,5-dithio-alpha- ( 29) and beta-D-xylopyranoside (30) in different ratios, depending on t he reaction conditions. When donor 18 was used in the presence of pota ssium carbonate, besides 29 and 30 two aryl C-glycosylated-thioglycosi des, i.e. ,4-tri-O-acetyl-5-thio-beta-D-xylopyranosyl)phenyl 2,3,4-tri -O-acetyl-1,5-dithio-alpha- and beta-D-xylopyranoside (32 and 33) as w ell as ,4-tri-O-acetyl-5-thio-beta-D-xylopyranosyl)phenyl disulfide 34 could be isolated as byproducts. Deacetylation of 30 with sodium meth oxide in methanol afforded, besides 4-cyanophenyl 1,5-dithio-beta-D-xy lopyrano side (1), the corresponding 4-[(methoxy)(imino)methyl]phenyl glycoside 2. The 4-cyano group of 1 was converted into the 4-aminothio carbonyl, the 4-(methylthio)(imino)methyl, the 4-amidino and the 4-(im ino)(hydrazino)methyl group. AII of these glycosides showed a signific ant antithrombotic activity on rats. (C) 1998 Elsevier Science Ltd. Al l rights reserved.