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【结 构 式】 
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【分子编号】64141 【品名】(3R)-3-methoxydecyl 4-methylbenzenesulfonate 【CA登记号】 |
【 分 子 式 】C18H30O4S 【 分 子 量 】342.4998 【元素组成】C 63.12% H 8.83% O 18.69% S 9.36% |
合成路线1
该中间体在本合成路线中的序号：(V)Saponification of (R)-methyl 3-hydroxydecanoate (I) gave hydroxy acid (II), which was reduced to diol (III) using LiAlH4. Selective sulfonylation of the primary hydroxyl group of (III) provided tosylate (IV). The secondary hydroxyl group of (IV) was subsequently alkylated with iodomethane in the presence of NaH to furnish the methyl ether (V).
| 【1】 Kobayashi, S.; Kawata, T.; Christ, W.J.; Rossignol, D.P. (Eisai Co., Ltd.); Substd. liposaccharides useful in the treatment and prevention of endotoxemia. US 5750664; WO 9639411 . |
| 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) | 59083 | methyl (3R)-3-hydroxydecanoate | C11H22O3 | 详情 | 详情 | |
| (II) | 64140 | (3R)-3-hydroxydecanoic acid | C10H20O3 | 详情 | 详情 | |
| (III) | 59084 | (3R)-1,3-decanediol | C10H22O2 | 详情 | 详情 | |
| (IV) | 49121 | (3R)-3-hydroxydecyl 4-methylbenzenesulfonate | C17H28O4S | 详情 | 详情 | |
| (V) | 64141 | (3R)-3-methoxydecyl 4-methylbenzenesulfonate | C18H30O4S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Treatment of D-glucosamine•HCl (VI) with ethyl trifluoroacetate and NaOMe produced the trifluoroacetamide (VII), which was subsequently acetylated with Ac2O yielding the tetraacetate (VIII). Displacement of the anomeric acetoxy group of (VIII) by allyl alcohol (IX) in the presence of SnCl4 furnished the allyl glucoside (X). After methanolysis of the acetate ester groups of (X), the resultant triol (XI) was protected as the acetonide (XII) by treatment with 2,2-dimethoxypropane and camphorsulfonic acid. Alkylation of the free hydroxyl group of (XII) with tosylate (V) under Williamson's ether synthesis conditions produced adduct (XIII). Selective hydrolysis of the acetonide moiety of (XIII) was accomplished by treatment with hydrofluoric acid to give diol (XIV). The primary hydroxyl of (XIV) was then converted to tosylate (XV) upon treatment with p-toluenesulfonyl chloride and DMAP.
| 【1】 Kobayashi, S.; Kawata, T.; Christ, W.J.; Rossignol, D.P. (Eisai Co., Ltd.); Substd. liposaccharides useful in the treatment and prevention of endotoxemia. US 5750664; WO 9639411 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (V) | 64141 | (3R)-3-methoxydecyl 4-methylbenzenesulfonate | C18H30O4S | 详情 | 详情 | |
| (VI) | 24036 | (3R,4R,5S,6R)-3-amino-6-(hydroxymethyl)tetrahydro-2H-pyran-2,4,5-triol; Glucosamine | 3416-24-8 | C6H13NO5 | 详情 | 详情 |
| (VII) | 64142 | 2,2,2-trifluoro-N-[(3R,4R,5S,6R)-2,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]acetamide | C8H12F3NO6 | 详情 | 详情 | |
| (VIII) | 64143 | (2R,3R,4R,5R)-4,6-bis(acetyloxy)-2-[(acetyloxy)methyl]-5-[(2,2,2-trifluoroacetyl)amino]tetrahydro-2H-pyran-3-yl acetate | C16H20F3NO10 | 详情 | 详情 | |
| (IX) | 12234 | 2-Propen-1-ol; Allyl alcohol | 107-18-6 | C3H6O | 详情 | 详情 |
| (X) | 64144 | (2R,3R,4R,5R)-3-(acetyloxy)-2-[(acetyloxy)methyl]-6-(allyloxy)-5-[(2,2,2-trifluoroacetyl)amino]tetrahydro-2H-pyran-4-yl acetate | C17H22F3NO9 | 详情 | 详情 | |
| (XI) | 64145 | N-[(3R,4R,5S,6R)-2-(allyloxy)-4,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-yl]-2,2,2-trifluoroacetamide | C11H16F3NO6 | 详情 | 详情 | |
| (XII) | 57540 | N-[(4aR,6S,7R,8R,8aS)-6-(allyloxy)-8-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]-2,2,2-trifluoroacetamide | C14H20F3NO6 | 详情 | 详情 | |
| (XIII) | 64146 | N-((4aR,7R,8R,8aS)-6-(allyloxy)-8-{[(3R)-3-methoxydecyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl)-2,2,2-trifluoroacetamide | C25H42F3NO7 | 详情 | 详情 | |
| (XIV) | 64147 | N-((3R,4R,5S,6R)-2-(allyloxy)-5-hydroxy-6-(hydroxymethyl)-4-{[(3R)-3-methoxydecyl]oxy}tetrahydro-2H-pyran-3-yl)-2,2,2-trifluoroacetamide | C22H38F3NO7 | 详情 | 详情 | |
| (XV) | 64148 | {(2R,3S,4R,5R)-6-(allyloxy)-3-hydroxy-4-{[(3R)-3-methoxydecyl]oxy}-5-[(2,2,2-trifluoroacetyl)amino]tetrahydro-2H-pyran-2-yl}methyl 4-methylbenzenesulfonate | C29H44F3NO9S | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(V)Hydroxy acid (II) was converted to methyl ether (XLI) by treatment with trimethylsilyl diazomethane. Reduction of acid (XLI) to alcohol (XLII) was accomplished by treatment with DIBAL in cold dichloromethane. Alcohol (XLII) was transformed to alkyl iodide (XLIII) via tosylation to (V), followed by displacement of tosylate (V) with NaI in acetone. Alkylation of the known azido sugar (XLIV) with the alkyl iodide (XLIII) in the presence of Ag2O provided ether (XLV). Then, acidic acetonide (XLV) hydrolysis led to diol (XLVI). Selective alkylation of the primary hydroxyl group of (XLVI) using iodomethane in the presence of Ag2O, followed by reprotection of some desilylated product, furnished the methyl ether (XLVII). The secondary hydroxyl group of (XLVII) was then converted to phosphate ester (XLVIII) employing the same phosphitylation/oxidation sequence as above.
| 【1】 Kobayashi, S.; Kawata, T.; Christ, W.J.; Rossignol, D.P. (Eisai Co., Ltd.); Substd. liposaccharides useful in the treatment and prevention of endotoxemia. US 5750664; WO 9639411 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 64140 | (3R)-3-hydroxydecanoic acid | C10H20O3 | 详情 | 详情 | |
| (V) | 64141 | (3R)-3-methoxydecyl 4-methylbenzenesulfonate | C18H30O4S | 详情 | 详情 | |
| (XLI) | 64173 | (3R)-3-methoxydecanoic acid | C11H22O3 | 详情 | 详情 | |
| (XLII) | 64174 | (3R)-3-methoxy-1-decanol | C11H24O2 | 详情 | 详情 | |
| (XLIII) | 64175 | (3R)-1-iodo-3-methoxydecane; (1R)-1-(2-iodoethyl)octyl methyl ether | C11H23IO | 详情 | 详情 | |
| (XLIV) | 59080 | (4aR,6S,7R,8R,8aS)-7-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-ol | C15H29N3O5Si | 详情 | 详情 | |
| (XLV) | 64176 | [((4aR,6S,7R,8R,8aS)-7-azido-8-{[(3R)-3-methoxydecyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)oxy](tert-butyl)dimethylsilane; (4aR,6S,7R,8R,8aS)-7-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-yl (3R)-3-methoxydecyl ether | C26H51N3O6Si | 详情 | 详情 | |
| (XLVI) | 64177 | (2R,3S,4R,5R,6S)-5-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-2-(hydroxymethyl)-4-{[(3R)-3-methoxydecyl]oxy}tetrahydro-2H-pyran-3-ol | C23H47N3O6Si | 详情 | 详情 | |
| (XLVII) | 64178 | (2R,3S,4R,5R,6S)-5-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-2-(methoxymethyl)tetrahydro-2H-pyran-3-ol | C24H49N3O6Si | 详情 | 详情 | |
| (XLVIII) | 64179 | diallyl (2R,3S,4R,5R,6S)-5-azido-6-{[tert-butyl(dimethyl)silyl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-2-(methoxymethyl)tetrahydro-2H-pyran-3-yl phosphate | C30H58N3O9PSi | 详情 | 详情 |