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【结 构 式】 
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【分子编号】30671 【品名】4-Benzyloxycarbonylamino-2-hydroxybutyric acid N-hydroxysuccinimide ester; Benzyl (3S)-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-3-hydroxy-4-oxobutylcarbamate 【CA登记号】 |
【 分 子 式 】C16H18N2O7 【 分 子 量 】350.3282 【元素组成】C 54.86% H 5.18% N 8% O 31.97% |
合成路线1
该中间体在本合成路线中的序号：(X)The acylation of 3',4'-dideoxykanamycin B (dibekacin) (I) with tert-butyl-S-(4,6-dimethylpyrimid-2-yl)thiocarbonate (VIII) by means of triethylamine in isopropanol gives 3,2',6'-tri-N-tert-butyloxycarbonyldibekacin (IX), which is acylated again with 4-benzyloxycarbonylamino-2-hydroxybutyric acid N-hydroxysuccinimide ester (X) in THE yielding the protected habekacin (XI). Finally, this compound is deprotected by a treatment with trifluoroacetic acid, followed by hydrogenolysis with H2 over Pd/C in methanol - acetic acid.
| 【1】 Umezawa, H.; Kondo, S. (Microbial Chemistry Research Foundation); Process for the preparation of 1-N-isoseryl- or 1-N-(L-4-amino-2-hydroxybutyryl)-3',4'-dideoxykanamycin B and intermediates thereof. DE 2950020; FR 2444046; GB 2038329; GB 2072676; GB 2072677; JP 55081897; US 4268664 . |
| 【2】 Serradell, M.N.; Castaner, J.; Blancafort, P.; Habekacin. Drugs Fut 1983, 8, 5, 410. |
| 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) | 30662 | Dibekacin; 3',4'-Dideoxykanamycin B; (2R,3R,4S,5S,6R)-4-amino-2-[((1S,2S,3R,4S,6R)-4,6-diamino-3-[[(2R,3R,6S)-3-amino-6-(aminomethyl)tetrahydro-2H-pyran-2-yl]oxy]-2-hydroxycyclohexyl)oxy]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol | C18H37N5O8 | 详情 | 详情 | |
| (VIII) | 30669 | tert-butyl-S-(4,6-dimethylpyrimid-2-yl)thiocarbonate; O-(tert-butyl) S-(4,6-dimethyl-2-pyrimidinyl) carbonothioate | 41840-28-2 | C11H16N2O2S | 详情 | 详情 |
| (IX) | 30670 | 3,2',6'-tri-N-tert-butyloxycarbonyldibekacin; tert-Butyl (2R,3R,4S,5S,6R)-2-([(1S,2S,3R,4S,6R)-6-amino-4-[(tert-butoxycarbonyl)amino]-3-[((2R,3R,6S)-3-[(tert-butoxycarbonyl)amino]-6-[[(tert-butoxycarbonyl)amino]methyl]tetrahydro-2H-pyran-2-yl)oxy]-2-hydroxycyclohexyl]oxy)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-ylcarbamate | C38H69N5O16 | 详情 | 详情 | |
| (X) | 30671 | 4-Benzyloxycarbonylamino-2-hydroxybutyric acid N-hydroxysuccinimide ester; Benzyl (3S)-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-3-hydroxy-4-oxobutylcarbamate | C16H18N2O7 | 详情 | 详情 | |
| (XI) | 30672 | benzyl (3S)-4-[((1R,2S,3S,4R,5S)-5-[(tert-butoxycarbonyl)amino]-4-[((2R,3R,6S)-3-[(tert-butoxycarbonyl)amino]-6-[[(tert-butoxycarbonyl)amino]methyl]tetrahydro-2H-pyran-2-yl)oxy]-2-[[(2R,3R,4S,5S,6R)-4-[(tert-butoxycarbonyl)amino]-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]-3-hydroxycyclohexyl)amino]-3-hydroxy-4-oxobutylcarbamate | C50H82N6O20 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(X)The acylation of 3',4'-dideoxy-3',4'-didehydrokanamycin B (XII) with tert-butyl-S-(4,6-dimethylpyrimid-2-yl)thiocarbonate (VIII) as before gives 3,2',6'-tri-N-butoxycarbonyl-3',4'-dideoxy-3',4'-didehydrokanamycin B (XIII), which is acylated again with (X) as before yielding the fully protected 3',4'-didehydrohabekacin (XIV). Partial deprotection of (XIV) with trifluoroacetic acid affords 1-N-(4-benzyloxycarbonylamino-2-hydroxybutyryl)-3',4'-dideoxy-3',4'-didehydrokanamycin B (XV), which is finally debenzylated and reduced by a treatment with H2 over PtO2 in aqueous acetic acid.
| 【1】 Serradell, M.N.; Castaner, J.; Blancafort, P.; Habekacin. Drugs Fut 1983, 8, 5, 410. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 30669 | tert-butyl-S-(4,6-dimethylpyrimid-2-yl)thiocarbonate; O-(tert-butyl) S-(4,6-dimethyl-2-pyrimidinyl) carbonothioate | 41840-28-2 | C11H16N2O2S | 详情 | 详情 |
| (X) | 30671 | 4-Benzyloxycarbonylamino-2-hydroxybutyric acid N-hydroxysuccinimide ester; Benzyl (3S)-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-3-hydroxy-4-oxobutylcarbamate | C16H18N2O7 | 详情 | 详情 | |
| (XII) | 30673 | 3',4'-dideoxy-3',4'-didehydrokanamycin B; (2R,3R,4S,5S,6R)-4-amino-2-[((1S,2S,3R,4S,6R)-4,6-diamino-3-[[(2R,3R,6S)-3-amino-6-(aminomethyl)-3,6-dihydro-2H-pyran-2-yl]oxy]-2-hydroxycyclohexyl)oxy]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,5-diol | C18H35N5O8 | 详情 | 详情 | |
| (XIII) | 30674 | 3,2',6'-tri-N-butoxycarbonyl-3',4'-dideoxy-3',4'-didehydrokanamycin B; tert-Butyl (2R,3R,4S,5S,6R)-2-([(1S,2S,3R,4S,6R)-6-amino-4-[(tert-butoxycarbonyl)amino]-3-[((2R,3R,6S)-3-[(tert-butoxycarbonyl)amino]-6-[[(tert-butoxycarbonyl)amino]methyl]-3,6-dihydro-2H-pyran-2-yl)oxy]-2-hydroxycyclohexyl]oxy)-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-ylcarbamate | C38H67N5O16 | 详情 | 详情 | |
| (XIV) | 30675 | tert-butyl (1S,2R,3S,4S,5R)-2-[[(2R,3R,6S)-3-amino-6-(aminomethyl)-3,6-dihydro-2H-pyran-2-yl]oxy]-5-[((2S)-4-[[(benzyloxy)carbonyl]amino]-2-hydroxybutanoyl)amino]-4-[[(2R,3R,4S,5S,6R)-4-[(tert-butoxycarbonyl)amino]-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]-3-hydroxycyclohexylcarbamate | C40H64N6O16 | 详情 | 详情 | |
| (XV) | 30676 | 1-N-(4-benzyloxycarbonylamino-2-Hydroxybutyryl)-3',4'-dideoxy-3',4'-didehydrokanamycin B; Benzyl (3S)-4-[((1R,2S,3S,4R,5S)-5-amino-4-[[(2R,3R,6S)-3-amino-6-(aminomethyl)-3,6-dihydro-2H-pyran-2-yl]oxy]-2-[[(2R,3R,4S,5S,6R)-4-amino-3,5-dihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]-3-hydroxycyclohexyl)amino]-3-hydroxy-4-oxobutylcarbamate | C30H48N6O12 | 详情 | 详情 |