Bozó E, Boros S, Kuszmann J, Gács-Baitz E, Párkányi L
Institute for Drug Research, Budapest, Hungary.
Carbohydr Res. 1998 Jun;308(3-4):297-310. doi: 10.1016/s0008-6215(98)00088-3.
D-Xylose was converted via 1,2-O-isopropylidene-alpha-D-xylofuranose (4) into 3-O-benzoyl-5-S-benzoyl-1,2-O-isopropylidene-alpha-D-xylofuranose which, after methanolysis, acetylation and subsequent acetolysis afforded 1,2,3,4-tetra-O-acetyl-5-thio-alpha-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-alpha-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-alpha-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 alpha-1-bromide 18 as well as into the alpha-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-alpha- (29) and beta-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-beta-D-xylopyranosyl)phenyl 2,3,4-tri-O-acetyl-1,5-dithio-alpha- and beta-D-xylopyranoside (32 and 33) as well as 4-cyano-2-(2,3,4-tri-O-acetyl-5-thio-beta-D-xylopyranosyl)phenyl disulfide 34 could be isolated as byproducts. Deacetylation of 30 with sodium methoxide in methanol afforded, besides 4-cyano-phenyl 1,5-dithio-beta-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-(methyl-thio)(imino)methyl, the 4-amidino and the 4-(imino)(hydrazino)methyl group. All of these glycosides showed a significant antithrombotic activity on rats.
D-木糖通过1,2-O-异亚丙基-α-D-木呋喃糖（4）转化为3-O-苯甲酰基-5-S-苯甲酰基-1,2-O-异亚丙基-α-D-木呋喃糖，该化合物在甲醇解、乙酰化及随后的乙酰解反应后，以36%的总收率得到1,2,3,4-四-O-乙酰基-5-硫代-α-D-吡喃木糖（14）。4与亚硫酰氯反应生成非对映异构体环状亚硫酸酯的混合物，其结构通过X射线晶体学确定。它们用高碘酸钠氧化得到相应的环状硫酸酯23。23用硫代乙酸钾处理得到5-S-乙酰基-1,2-O-异亚丙基-α-D-木呋喃糖3-O-磺酸的钾盐（26），该化合物在甲醇解、乙酰化及随后的乙酰解反应后，以56%的总收率得到14。4与硫酰氯反应得到一种混合物，其中包含5-氯-3-O-氯磺酰基-5-脱氧-1,2-O-异亚丙基-α-D-木呋喃糖、3,7,9,11-四氧杂-4-硫杂-10-二甲基三环[6,3,0,0(2,6)]十一烷S-二氧化物和23，其比例为2:3:7。四乙酸酯14转化为α-1-溴化物18以及α-1-O-三氯乙酰亚胺酯17。这三种化合物用作与4-氰基硫酚进行糖基化反应的供体，根据反应条件，以不同比例得到4-氰基苯基2,3,4-三-O-乙酰基-1,5-二硫代-α-（29）和β-D-吡喃木糖苷（30）。当在碳酸钾存在下使用供体18时，除了29和30之外，还可分离出两种芳基C-糖基化硫代糖苷作为副产物，即4-氰基-2-(2,3,4-三-O-乙酰基-5-硫代-β-D-吡喃木糖基)苯基2,3,4-三-O-乙酰基-1,5-二硫代-α-和β-D-吡喃木糖苷（32和33）以及4-氰基-2-(2,3,4-三-O-乙酰基-5-硫代-β-D-吡喃木糖基)苯基二硫化物34。30在甲醇中用甲醇钠脱乙酰化，除了得到4-氰基苯基1,5-二硫代-β-D-吡喃木糖苷（1）之外，还得到相应的4-[(甲氧基)(亚氨基)甲基]苯基糖苷2。1的4-氰基转化为4-氨基硫羰基、4-(甲硫基)(亚氨基)甲基基团、4-脒基和4-(亚氨基)(肼基)甲基基团。所有这些糖苷在大鼠身上均表现出显著的抗血栓活性。
