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【结 构 式】 
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【分子编号】40615 【品名】(1R)-1-[2-[((2R,3R,4R,5R,6R)-2-(benzyloxy)-5-hydroxy-6-(hydroxymethyl)-4-[[(2,2,2-trichloroethoxy)carbonyl]oxy]tetrahydro-2H-pyran-3-yl)amino]-2-oxoethyl]dodecyl myristate 【CA登记号】 |
【 分 子 式 】C44H72Cl3NO10 【 分 子 量 】881.41452 【元素组成】C 59.96% H 8.23% Cl 12.07% N 1.59% O 18.15% |
合成路线1
该中间体在本合成路线中的序号：(V)Acylation of amino alcohol (I) with (R)-3-(n-tetradecanoyloxy)tetradecanoic acid (II) employing 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide methiodide (EDC.MeI) provided amide (III). After hydroxyl group protection with 2,2,2-trichloroethyl chloroformate (A), the resulting acetonide (IV) was hydrolyzed with aqueous AcOH to give (V).
| 【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 |
|---|---|---|---|---|---|---|
| (A) | 13664 | 1,1,1-Trichloro-2-[(chlorocarbonyl)oxy]ethane; 2,2,2-Trichloroethyl chloroformate | 17341-93-4 | C3H2Cl4O2 | 详情 | 详情 |
| (I) | 16046 | (4aR,6R,7R,8R,8aS)-7-amino-6-(benzyloxy)-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-8-ol | C16H23NO5 | 详情 | 详情 | |
| (II) | 40612 | (3R)-3-(tetradecanoyloxy)tetradecanoic acid | C28H54O4 | 详情 | 详情 | |
| (III) | 40613 | (1R)-1-(2-[[(4aR,6R,7R,8R,8aS)-6-(benzyloxy)-8-hydroxy-2,2-dimethylhexahydropyrano[3,2-d][1,3]dioxin-7-yl]amino]-2-oxoethyl)dodecyl myristate | C44H75NO8 | 详情 | 详情 | |
| (IV) | 40614 | (1R)-1-[2-[((4aR,6R,7R,8R,8aR)-6-(benzyloxy)-2,2-dimethyl-8-[[(2,2,2-trichloroethoxy)carbonyl]oxy]hexahydropyrano[3,2-d][1,3]dioxin-7-yl)amino]-2-oxoethyl]dodecyl myristate | C47H76Cl3NO10 | 详情 | 详情 | |
| (V) | 40615 | (1R)-1-[2-[((2R,3R,4R,5R,6R)-2-(benzyloxy)-5-hydroxy-6-(hydroxymethyl)-4-[[(2,2,2-trichloroethoxy)carbonyl]oxy]tetrahydro-2H-pyran-3-yl)amino]-2-oxoethyl]dodecyl myristate | C44H72Cl3NO10 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Coupling of glycosyl chloride (XII) with glycoside (V) in the presence of silver triflate gave rise to the corresponding beta-disaccharide and subsequent reductive cleavage of the trichloro ethyl-based protecting groups with Zn/AcOH yielded disaccharide (XIII). Further N-acylation of (XIII) with acid (II) in the presence of 2-ethoxy-1-(ethoxycarbonyl)-1,2-dihydroquinoline (EEDQ) furnished amide (XIV). Finally, two-step hydrogenolytic deprotection of the benzyl and phenyl groups of (XIV) and lyophilization in the presence of triethylamine provided the title compound.
| 【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 |
|---|---|---|---|---|---|---|
| (II) | 40612 | (3R)-3-(tetradecanoyloxy)tetradecanoic acid | C28H54O4 | 详情 | 详情 | |
| (V) | 40615 | (1R)-1-[2-[((2R,3R,4R,5R,6R)-2-(benzyloxy)-5-hydroxy-6-(hydroxymethyl)-4-[[(2,2,2-trichloroethoxy)carbonyl]oxy]tetrahydro-2H-pyran-3-yl)amino]-2-oxoethyl]dodecyl myristate | C44H72Cl3NO10 | 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 | |
| (XIII) | 40617 | C87H143N2O18P | 详情 | 详情 | ||
| (XIV) | 40618 | C115H195N2O21P | 详情 | 详情 |