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【结 构 式】 
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【分子编号】57548 【品名】(1R)-1-{2-[((2S,3R,4R,5S,6R)-2-(allyloxy)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-[(diphenoxyphosphoryl)oxy]-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-4-yl)oxy]ethyl}dodecyl myristate 【CA登记号】 |
【 分 子 式 】C58H95Cl3NO12PSi 【 分 子 量 】1163.809202 【元素组成】C 59.86% H 8.23% Cl 9.14% N 1.2% O 16.5% P 2.66% Si 2.41% |
合成路线1
该中间体在本合成路线中的序号：(XXV)The primary hydroxyl of (XXI) is protected as the silyl ether (XXII) by means of t-butyldimethylsilyl chloride and DMAP. Subsequent phosphorylation of the remaining secondary hydroxyl group with diphenylphosphoryl chloride gives phosphate ester (XXIII). Removal of the p-methoxybenzyl protecting group of (XXIII) is accomplished by oxidative cleavage with DDQ, yielding alcohol (XXIV), which is acylated by myristoyl chloride, to produce ester (XXV). Desilylation of (XXV) under acidic conditions affords alcohol (XXVI), which is converted to methyl ether (XXVII) using trimethyloxonium fluoborate as the alkylating reagent. Iridium-catalyzed deallylation of the allyl glucoside (XXVII) furnishes the cyclic glucosamine (XXVIII).
| 【1】 Nishijima, M.; Kurakata, S.-I.; Shiozaki, M.; Mochizuki, T.; Kanai, S.; Watanabe, Y.; Synthesis of lipid A type pyran carboxylic acids with ether chains and their biological activities. Carbohydr Res 2001, 333, 3, 203. |
| 【2】 Shiozaki, M.; Kurakata, S.; Kanai, S.; Kazama, Y. (Sankyo Co., Ltd.); Ether type lipid A1-carboxylic acid analogues. EP 1152007; JP 2000297096; US 2002161221; US 6511965; WO 0047595 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 30295 | tetradecanoyl chloride | 112-64-1 | C14H27ClO | 详情 | 详情 | |
| (XXI) | 57544 | 2,2,2-trichloroethyl (2S,3R,4R,5S,6R)-2-(allyloxy)-4-{[(3R)-3-(2-[1,1'-biphenyl]-4-ylethoxy)tetradecyl]oxy}-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-3-ylcarbamate | C40H58Cl3NO8 | 详情 | 详情 | |
| (XXII) | 57545 | 4-{2-[((1R)-1-{2-[((2S,3R,4R,5S,6R)-2-(allyloxy)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-hydroxy-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-4-yl)oxy]ethyl}dodecyl)oxy]ethyl}-1,1'-biphenyl; 2,2,2-trichloroethyl (2S,3R,4R,5S,6R)-2-(allyloxy)-4-{[(3R)-3-(2-[1,1'-biphenyl]-4-ylethoxy)tetradecyl]oxy}-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-hydroxytetrahydro-2H-pyran-3-ylcarbamate | C46H72Cl3NO8Si | 详情 | 详情 | |
| (XXIII) | 57546 | 4-{2-[((1R)-1-{2-[((2S,3R,4R,5S,6R)-2-(allyloxy)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-[(diphenoxyphosphoryl)oxy]-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-4-yl)oxy]ethyl}dodecyl)oxy]ethyl}-1,1'-biphenyl; 2,2,2-trichloroethyl (2S,3R,4R,5S,6R)-2-(allyloxy)-4-{[(3R)-3-(2-[1,1'-biphenyl]-4-ylethoxy)tetradecyl]oxy}-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-[(diphenoxyphosphoryl)oxy]tetrahydro-2H-pyran-3-ylcarbamate | C58H81Cl3NO11PSi | 详情 | 详情 | |
| (XXIV) | 57547 | 2,2,2-trichloroethyl (2S,3R,4R,5S,6R)-2-(allyloxy)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-[(diphenoxyphosphoryl)oxy]-4-{[(3R)-3-hydroxytetradecyl]oxy}tetrahydro-2H-pyran-3-ylcarbamate | C44H69Cl3NO11PSi | 详情 | 详情 | |
| (XXV) | 57548 | (1R)-1-{2-[((2S,3R,4R,5S,6R)-2-(allyloxy)-6-({[tert-butyl(dimethyl)silyl]oxy}methyl)-5-[(diphenoxyphosphoryl)oxy]-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-4-yl)oxy]ethyl}dodecyl myristate | C58H95Cl3NO12PSi | 详情 | 详情 | |
| (XXVI) | 57549 | (1R)-1-{2-[((2S,3R,4R,5S,6R)-2-(allyloxy)-5-[(diphenoxyphosphoryl)oxy]-6-(hydroxymethyl)-3-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-4-yl)oxy]ethyl}dodecyl myristate | C52H81Cl3NO12P | 详情 | 详情 | |
| (XXVII) | 57550 | 2,2,2-trichloroethyl (2S,3R,4R,5S,6R)-2-(allyloxy)-5-[(diphenoxyphosphoryl)oxy]-4-{[(3R)-3-(formyloxy)tetradecyl]oxy}-6-(methoxymethyl)tetrahydro-2H-pyran-3-ylcarbamate | C40H57Cl3NO12P | 详情 | 详情 | |
| (XXVIII) | 57551 | (1R)-1-{2-[((2R,3S,4R,5R)-3-[(diphenoxyphosphoryl)oxy]-6-hydroxy-2-(methoxymethyl)-5-{[(2,2,2-trichloroethoxy)carbonyl]amino}tetrahydro-2H-pyran-4-yl)oxy]ethyl}dodecyl myristate | C50H79Cl3NO12P | 详情 | 详情 |