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【结 构 式】 
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【分子编号】39769 【品名】(4aR,6R,7R,8R,8aS)-7-amino-2,2-dimethyl-6-[2-(trimethylsilyl)ethoxy]hexahydropyrano[3,2-d][1,3]dioxin-8-ol 【CA登记号】 |
【 分 子 式 】C14H29NO5Si 【 分 子 量 】319.4735 【元素组成】C 52.63% H 9.15% N 4.38% O 25.04% Si 8.79% |
合成路线1
该中间体在本合成路线中的序号：(VI)N-Protection of amino alcohol (VI) under Schotten-Baumann conditions with 2,2,2-trichloroethyl chloroformate (B) aforded carbamate (VII). Subsequent esterification of (VII) with acid (II) provided (VIII), which was followed by acetonide hydrolysis to give diol (IX). Selective protection of the primary hydroxyl of (IX) with 1,1-dimethyl-2,2,2-trichloroethyl chloroformate (C) furnished carbonate (X). Further phosphorylation of the free secondary hydroxyl of (X) with diphenylphosphoryl chloride (D) produced phosphate ester (XI). Conversion of the trimethylsily-ethyl glycoside (XI) into the desired glycosyl chloride (XII) was then accomplished by treatment with alpha,alpha-dichloromethyl methyl ether and ZnCl2.
| 【1】 Sowell, C.G.; Johnson, D.A.; Keegan, D.S.; et al.; 3-O-Desacyl monophosphoryl lipid A derivatives: Synthesis and immunostimulant activities. J Med Chem 1999, 42, 22, 4640. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 13664 | 1,1,1-Trichloro-2-[(chlorocarbonyl)oxy]ethane; 2,2,2-Trichloroethyl chloroformate | 17341-93-4 | C3H2Cl4O2 | 详情 | 详情 |
| (D) | 16074 | Diphenyl phosphoryl chloride; 1,1'-Diphenylphosphoryl chloride; Chlorodiphenyl Phosphate; Diphenyl chlorophosphate; Diphenylchlorophosphate | 2524-64-3 | C12H10ClO3P | 详情 | 详情 |
| (II) | 40612 | (3R)-3-(tetradecanoyloxy)tetradecanoic acid | C28H54O4 | 详情 | 详情 | |
| (VI) | 39769 | (4aR,6R,7R,8R,8aS)-7-amino-2,2-dimethyl-6-[2-(trimethylsilyl)ethoxy]hexahydropyrano[3,2-d][1,3]dioxin-8-ol | C14H29NO5Si | 详情 | 详情 | |
| (VII) | 39770 | 2,2,2-trichloroethyl (4aR,6R,7R,8R,8aS)-8-hydroxy-2,2-dimethyl-6-[2-(trimethylsilyl)ethoxy]hexahydropyrano[3,2-d][1,3]dioxin-7-ylcarbamate | C17H30Cl3NO7Si | 详情 | 详情 | |
| (VIII) | 39772 | (4aR,6R,7R,8R,8aR)-2,2-dimethyl-7-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]hexahydropyrano[3,2-d][1,3]dioxin-8-yl (3R)-3-(tetradecanoyloxy)tetradecanoate | C45H82Cl3NO10Si | 详情 | 详情 | |
| (IX) | 39773 | (2R,3R,4R,5R,6R)-3-hydroxy-2-(hydroxymethyl)-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate | C42H78Cl3NO10Si | 详情 | 详情 | |
| (X) | 39774 | (2R,3R,4R,5R,6R)-3-hydroxy-2-([[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]oxy]methyl)-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate | C47H83Cl6NO12Si | 详情 | 详情 | |
| (XI) | 39775 | (2R,3R,4R,5R,6R)-3-[(diphenoxyphosphoryl)oxy]-2-([[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]oxy]methyl)-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate | C59H92Cl6NO15PSi | 详情 | 详情 | |
| (XII) | 40616 | (2R,3R,4R,5S,6R)-2-chloro-5-[(diphenoxyphosphoryl)oxy]-6-([[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]oxy]methyl)-3-[[(2,2,2-trichloroethoxy)carbonyl]amino]tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate | C54H79Cl7NO14P | 详情 | 详情 | |
| (C) | 38221 | 1,1,1-trichloro-2-[(chlorocarbonyl)oxy]-2-methylpropane | C5H6Cl4O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)Protection of the amino group of aminopyranoside (VI) with 2,2,2-trichloroethyl chloroformate under Schotten-Baumann conditions afforded trichloroethyl carbamate (VII). Subsequent O-acylation of (VII) with acid chloride (VIII) gave ester (IX). Acetonide (IX) cleavage with aqueous AcOH yielded diol (X), which was protected at the primary hydroxyl group using 1,1-dimethyl-2,2,2-trichloroethyl chloroformate yielding (XI). Conversion of (XI) to the required phosphate (XII) was effected by reaction with diphenyl chlorophosphate. The intermediate glycosyl chloride (XIII) was then obtained by treatment of (XII) with dichloromethyl methyl ether and ZnCl2.
| 【1】 Sowell, C.G.; Weber, P.A.; Elliott, G.T. (Corixa Corp.); Phosphoglycolipid and methods for its use. WO 0011010 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 39769 | (4aR,6R,7R,8R,8aS)-7-amino-2,2-dimethyl-6-[2-(trimethylsilyl)ethoxy]hexahydropyrano[3,2-d][1,3]dioxin-8-ol | C14H29NO5Si | 详情 | 详情 | |
| (VII) | 39770 | 2,2,2-trichloroethyl (4aR,6R,7R,8R,8aS)-8-hydroxy-2,2-dimethyl-6-[2-(trimethylsilyl)ethoxy]hexahydropyrano[3,2-d][1,3]dioxin-7-ylcarbamate | C17H30Cl3NO7Si | 详情 | 详情 | |
| (VIII) | 39771 | (1R)-1-(2-chloro-2-oxoethyl)dodecyl myristate | C28H53ClO3 | 详情 | 详情 | |
| (IX) | 39772 | (4aR,6R,7R,8R,8aR)-2,2-dimethyl-7-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]hexahydropyrano[3,2-d][1,3]dioxin-8-yl (3R)-3-(tetradecanoyloxy)tetradecanoate | C45H82Cl3NO10Si | 详情 | 详情 | |
| (X) | 39773 | (2R,3R,4R,5R,6R)-3-hydroxy-2-(hydroxymethyl)-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate | C42H78Cl3NO10Si | 详情 | 详情 | |
| (XI) | 39774 | (2R,3R,4R,5R,6R)-3-hydroxy-2-([[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]oxy]methyl)-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate | C47H83Cl6NO12Si | 详情 | 详情 | |
| (XII) | 39775 | (2R,3R,4R,5R,6R)-3-[(diphenoxyphosphoryl)oxy]-2-([[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]oxy]methyl)-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]-6-[2-(trimethylsilyl)ethoxy]tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate | C59H92Cl6NO15PSi | 详情 | 详情 | |
| (XIII) | 39776 | (2R,3R,4R,5S,6R)-2-chloro-5-[(diphenoxyphosphoryl)oxy]-3-[(ethoxycarbonyl)amino]-6-([[(2,2,2-trichloro-1,1-dimethylethoxy)carbonyl]oxy]methyl)tetrahydro-2H-pyran-4-yl (3R)-3-(tetradecanoyloxy)tetradecanoate | C54H82Cl4NO14P | 详情 | 详情 |