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【结 构 式】 
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【药物名称】GYKI-39541, RGH-1962 【化学名称】1-(4-Nitrophenylsulfanyl)-1,5-dithio-beta-D-arabinopyranoside 【CA登记号】218907-16-5 【 分 子 式 】C11H13NO5S2 【 分 子 量 】303.35796 |
【开发单位】Gedeon Richter (Originator) 【药理作用】Anticoagulants, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS |
合成路线1
The thiobenzoylation of the readily available 2,3-O-isopropylidene-5-O-tosyl-L-arabinose diethyl dithioacetal (I) gives the 5-S-thiobenzoate (II), which is treated with HgO and BF3/Et2O in THF/water gives the corresponding aldehyde (III). The cyclization of (III) with NaOMe in methanol affords the cyclic arabinopyranose (IV), which is deprotected with AcOH giving 5-O-benzoyl-beta-D-arabinopyranose (V). The acetylation of (V) with Ac2O yields the triacetate (VI), which is condensed with 4-nitrothiophenol (VII) by means of K2CO3 in refluxing acetone affording the acylated dithio-beta-D-arabinopyranoside (VIII). Finally, this compound is deacylated with NaOMe in MeOH.
| 【1】 Bozo, E.; Boros, S.; Kuszmann, J.; Synthesis of 4-cyanophenyl and 4-nitrophenyl 1,5-dithio-L- and -D-arabinopyranosides possessing antithrombotic activity. Carbohydr Res 1998, 311, 4, 191. |
| 【2】 Szeker, G.; Boros, S.; Szabó, G.; Turuczné Ferwagner, M.; Orbán, O.; Feher, B.; Soukupné Kedves, R.; Kenyeres, L.; Kovácsné Bozó, E.; Barabás, É.; Moravcsik, I.; Kaszás, E.; Kuszmann, J. (Gedeon Richter Ltd.); Novel anticoagulant glycosides and pharmaceutical compsns. thereof. WO 9928312 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 38892 | (2S)-2-[(4S,5R)-5-[bis(ethylsulfanyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethyl 4-methylbenzenesulfonate | C19H30O6S3 | 详情 | 详情 | |
| (II) | 38893 | S-((2R)-2-[(4S,5R)-5-[bis(ethylsulfanyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethyl) benzenecarbothioate | C19H28O4S3 | 详情 | 详情 | |
| (III) | 38894 | S-[(2R)-2-[(4S,5R)-5-formyl-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethyl] benzenecarbothioate | C15H18O5S | 详情 | 详情 | |
| (IV) | 38895 | (3aR,4R,7R,7aR)-4-hydroxy-2,2-dimethyltetrahydro-4H-thiopyrano[3,4-d][1,3]dioxol-7-yl benzoate | C15H18O5S | 详情 | 详情 | |
| (V) | 38896 | (3R,4R,5R,6R)-4,5,6-trihydroxytetrahydro-2H-thiopyran-3-yl benzoate | C12H14O5S | 详情 | 详情 | |
| (VI) | 38897 | (3R,4R,5R,6R)-4,5,6-tris(acetoxy)tetrahydro-2H-thiopyran-3-yl benzoate | C18H20O8S | 详情 | 详情 | |
| (VII) | 38898 | 4-nitrophenylhydrosulfide; 4-nitrobenzenethiol | 1849-36-1 | C6H5NO2S | 详情 | 详情 |
| (VIII) | 38899 | (3R,4R,5R,6S)-4,5-bis(acetoxy)-6-[(4-nitrophenyl)sulfanyl]tetrahydro-2H-thiopyran-3-yl benzoate | C22H21NO8S2 | 详情 | 详情 |