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【结 构 式】 
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【分子编号】64179 【品名】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 【CA登记号】 |
【 分 子 式 】C30H58N3O9PSi 【 分 子 量 】663.864602 【元素组成】C 54.28% H 8.81% N 6.33% O 21.69% P 4.67% Si 4.23% |
合成路线1
该中间体在本合成路线中的序号：(XLVIII)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 |
合成路线2
该中间体在本合成路线中的序号：(XLVIII)Azido sugar (XLVIII) was reduced to the corresponding amine (XLIX) employing the in situ generated tin tris(benzenthiolate) triethylamine complex. Amine (XLIX) was then protected as the trichloethyl carbamate (L) by treatment with Troc-chloride and pyridine. After desilylation of (L) with HF, the resultant alcohol was activated as the trichloroacetimidate (XXXIV) as in Scheme 27814501e.
| 【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 |
|---|---|---|---|---|---|---|
| (XXXIV) | 64166 | (3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-2-yl 2,2,2-trichloroethanimidoate | C29H47Cl6N2O11P | 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 | |
| (XLIX) | 64180 | diallyl (2R,3S,4R,5R,6S)-5-amino-6-{[tert-butyl(dimethyl)silyl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-2-(methoxymethyl)tetrahydro-2H-pyran-3-yl phosphate | C30H60NO9PSi | 详情 | 详情 | |
| (L) | 64181 | 2,2,2-trichloroethyl (2S,3R,4R,5S,6R)-5-{[bis(allyloxy)phosphoryl]oxy}-2-{[tert-butyl(dimethyl)silyl]oxy}-4-{[(3R)-3-methoxydecyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-3-ylcarbamate | C33H61Cl3NO11PSi | 详情 | 详情 |