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【结 构 式】 
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【分子编号】54147 【品名】(4aS,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl methyl ether; (4aS,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-7,8-dimethoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine 【CA登记号】n/a |
【 分 子 式 】C39H50O11 【 分 子 量 】694.8194 【元素组成】C 67.42% H 7.25% O 25.33% |
合成路线1
该中间体在本合成路线中的序号：(VI)Glycosylation of sugar (I) with the idopyranosyl fluoride (II) by means of BF3.Et2O and molecular sieves in dichloromethane gives the disaccharide fragment (III), which is then converted into acetonide (V) by saponification of the ester functions with t-BuOK, followed by reaction with 2,2-dimethoxypropane (IV) in DMF and acidification with p-toluensulfonic acid. Methylation of acetonide (V) with MeI and NaH in DMF/MeOH provides the disaccharide (VI), which is then treated with HOAc to yield the 4',6'-diol (VII). Selective silylation of the diol (VII) with tert-butyldimethylsilyl chloride (TBDMSCl) in pyridine leads to the 6'-O-TBDMS derivative (VIII), which is condensed with levulinic acid (IX) by means of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) in dioxane to give the ester (X). Compound (X) is then submitted to simultaneous Jones oxidation and TBDMS removal with CrO3 and H2SO4/H2O in acetone to provide the iduronic acid derivative (XI), which is converted into the key intermediate (XII), first by esterification with MeI and KHCO3 in DMF and then by removal of the 4'-O-levulinoyl protecting group with HOAc and hydrazine hydrate in pyridine.
| 【1】 del Fresno, M.; Diaz-Ricart, M.; Idraparinux Sodium. Drugs Fut 2002, 27, 7, 639. |
| 【2】 Basten, J.E.M.; van Boeckel, C.A.A.; Westerduin, P.; et al.; Feasible synthesis and biological properties of six "non-glycosamino" glycan analogues of the antithrombin III binding heparin pentasaccharide. Bioorg Med Chem 1994, 2, 11, 1267. |
| 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) | 54143 | (2R,3S,4S,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-ol | n/a | C28H32O6 | 详情 | 详情 |
| (II) | 54144 | (2S,3S,4S,5R)-5-(acetyloxy)-2-[(acetyloxy)methyl]-6-fluoro-4-methoxytetrahydro-2H-pyran-3-yl acetate | n/a | C13H19FO8 | 详情 | 详情 |
| (III) | 54145 | (2R,3R,4S,5S,6S)-5-(acetyloxy)-6-[(acetyloxy)methyl]-2-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-4-methoxytetrahydro-2H-pyran-3-yl acetate | n/a | C41H50O14 | 详情 | 详情 |
| (IV) | 10722 | 1-Methoxy-1-methylethyl methyl ether; 2,2-Dimethoxypropane | 77-76-9 | C5H12O2 | 详情 | 详情 |
| (V) | 54146 | (4aS,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-8-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-ol | n/a | C38H48O11 | 详情 | 详情 |
| (VI) | 54147 | (4aS,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-7-methoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl methyl ether; (4aS,6R,7R,8R,8aS)-6-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-7,8-dimethoxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxine | n/a | C39H50O11 | 详情 | 详情 |
| (VII) | 54148 | (2S,3S,4S,5R,6S)-6-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-2-(hydroxymethyl)-4,5-dimethoxytetrahydro-2H-pyran-3-ol | n/a | C36H46O11 | 详情 | 详情 |
| (VIII) | 54149 | (2S,3S,4S,5R,6S)-6-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4,5-dimethoxytetrahydro-2H-pyran-3-ol | n/a | C42H60O11Si | 详情 | 详情 |
| (IX) | 36170 | 4-oxopentanoic acid | 123-76-2 | C5H8O3 | 详情 | 详情 |
| (X) | 54150 | (2S,3S,4R,5R,6R)-6-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4,5-dimethoxytetrahydro-2H-pyran-3-yl 4-oxopentanoate | n/a | C47H66O13Si | 详情 | 详情 |
| (XI) | 54151 | (2R,3S,4R,5R,6R)-6-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-4,5-dimethoxy-3-[(4-oxopentanoyl)oxy]tetrahydro-2H-pyran-2-carboxylic acid | n/a | C41H50O14 | 详情 | 详情 |
| (XII) | 54152 | methyl (2R,3S,4S,5R,6R)-6-({(2R,3S,4R,5R,6S)-4,5-bis(benzyloxy)-2-[(benzyloxy)methyl]-6-methoxytetrahydro-2H-pyran-3-yl}oxy)-3-hydroxy-4,5-dimethoxytetrahydro-2H-pyran-2-carboxylate | n/a | C37H46O12 | 详情 | 详情 |