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【结 构 式】 
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【分子编号】41412 【品名】(2S)-3-[((2R,3R,4R,5R,6R)-4,5-bis(acetoxy)-6-[(acetoxy)methyl]-3-[[(3R)-3-(tetradecanoyloxy)tetradecanoyl]amino]tetrahydro-2H-pyran-2-yl)oxy]-2-(tetradecanoylamino)propionic acid 【CA登记号】 |
【 分 子 式 】C57H102N2O14 【 分 子 量 】1039.44196 【元素组成】C 65.86% H 9.89% N 2.7% O 21.55% |
合成路线1
该中间体在本合成路线中的序号：(VII)Phenylsulfanyl glycoside (I) was coupled with serine derivative (II) in the presence of N-bromosuccinimide, iodine and tetrabutylammonium triflate yielding the serine glycoside (III). Reductive cleavage of the trichloroethoxy carbonyl group of (III) with Zn and HOAc afforded amine (IV), which was acylated with (R)-3-(tetradecanoyloxy)tetradecanoic acid (V) using DCC and HOBt. Hydrogenolysis of the benzyl ester (VI) over palladium black provided carboxylic acid (VII).
| 【1】 Ikeda, K.; et al.; Lipid A and related compounds. XXXVII. Determination of favorable binding linkages of lipid A analog to antigen moiety for synthetic vaccines. Chem Pharm Bull 2000, 48, 1, 32. |
| 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) | 41407 | (2R,3S,4R,5R,6S)-3-(acetoxy)-2-[(acetoxy)methyl]-6-(phenylsulfanyl)-5-[[(2,2,2-trichloroethoxy)carbonyl]amino]tetrahydro-2H-pyran-4-yl acetate | C21H24Cl3NO9S | 详情 | 详情 | |
| (II) | 41408 | benzyl (2S)-3-hydroxy-2-(tetradecanoylamino)propanoate | C24H39NO4 | 详情 | 详情 | |
| (III) | 41409 | benzyl (2S)-3-[((2R,3R,4R,5R,6R)-4,5-bis(acetoxy)-6-[(acetoxy)methyl]-3-[[(2,2,2-trichloroethoxy)carbonyl]amino]tetrahydro-2H-pyran-2-yl)oxy]-2-(tetradecanoylamino)propanoate | C39H57Cl3N2O13 | 详情 | 详情 | |
| (IV) | 41410 | benzyl (2S)-3-([(2R,3R,4R,5R,6R)-4,5-bis(acetoxy)-6-[(acetoxy)methyl]-3-aminotetrahydro-2H-pyran-2-yl]oxy)-2-(tetradecanoylamino)propanoate | C36H56N2O11 | 详情 | 详情 | |
| (V) | 40612 | (3R)-3-(tetradecanoyloxy)tetradecanoic acid | C28H54O4 | 详情 | 详情 | |
| (VI) | 41411 | (1R)-1-[2-[((2R,3R,4R,5R,6R)-4,5-bis(acetoxy)-6-[(acetoxy)methyl]-2-[[(2S)-3-(benzyloxy)-3-oxo-2-(tetradecanoylamino)propyl]oxy]tetrahydro-2H-pyran-3-yl)amino]-2-oxoethyl]dodecyl myristate | C64H108N2O14 | 详情 | 详情 | |
| (VII) | 41412 | (2S)-3-[((2R,3R,4R,5R,6R)-4,5-bis(acetoxy)-6-[(acetoxy)methyl]-3-[[(3R)-3-(tetradecanoyloxy)tetradecanoyl]amino]tetrahydro-2H-pyran-2-yl)oxy]-2-(tetradecanoylamino)propionic acid | C57H102N2O14 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Intermediate (VII) was coupled with beta-alanine benzyl ester (VIII) to give amide (IX). After hydrogenolysis of the benzyl ester of (IX), the acetate esters were removed by treatment with ammonia in MeOH, THF.
| 【1】 Miyajima, K.; Nekado, T.; Ikeda, K.; Achiwa, K.; Synthesis of Tn, sialyl Tn and HIV-1-derived peptide antigen conjugates having a lipid A analog as an immunoadjuvant for synthetic vaccines. Chem Pharm Bull 1998, 46, 11, 1676. |
| 【2】 Ikeda, K.; et al.; Lipid A and related compounds. XXXVII. Determination of favorable binding linkages of lipid A analog to antigen moiety for synthetic vaccines. Chem Pharm Bull 2000, 48, 1, 32. |
| 【3】 Miyajima, K.; et al.; Synthesis of TN and sialyl TN antigen-lipid an analog conjugates for synthetic vaccines. Chem Pharm Bull 1997, 45, 9, 1544. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 41412 | (2S)-3-[((2R,3R,4R,5R,6R)-4,5-bis(acetoxy)-6-[(acetoxy)methyl]-3-[[(3R)-3-(tetradecanoyloxy)tetradecanoyl]amino]tetrahydro-2H-pyran-2-yl)oxy]-2-(tetradecanoylamino)propionic acid | C57H102N2O14 | 详情 | 详情 | |
| (VIII) | 30194 | benzyl 3-aminopropanoate | 27019-47-2 | C10H13NO2 | 详情 | 详情 |
| (IX) | 41413 | (1R)-1-[2-[((2R,3R,4R,5R,6R)-4,5-bis(acetoxy)-6-[(acetoxy)methyl]-2-[[(2S)-3-[[3-(benzyloxy)-3-oxopropyl]amino]-3-oxo-2-(tetradecanoylamino)propyl]oxy]tetrahydro-2H-pyran-3-yl)amino]-2-oxoethyl]dodecyl myristate | C67H113N3O15 | 详情 | 详情 | |
| (X) | 41414 | N-[(2S)-3-[((2R,3R,4R,5R,6R)-4,5-bis(acetoxy)-6-[(acetoxy)methyl]-3-[[(3R)-3-(tetradecanoyloxy)tetradecanoyl]amino]tetrahydro-2H-pyran-2-yl)oxy]-2-(tetradecanoylamino)propanoyl]-beta-alanine | C60H107N3O15 | 详情 | 详情 |