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【结 构 式】 
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【药物名称】Murabutide 【化学名称】2-Acetamido-3-O-[(R)-1-[[(S)-3-carbamoyl-1-carboxypropyl]carbamoyl]ethyl]carbamoyl]ethyl]-2-deoxy-D-glucopyranose butyl ester 【CA登记号】74817-61-1 【 分 子 式 】C23H40N4O11 【 分 子 量 】548.59545 |
【开发单位】Choay (Originator), Institut Pasteur (Originator) 【药理作用】IMMUNOMODULATING AGENTS, Immunomodulators |
合成路线1
The reaction of N-benzltoxycarbonyl-L-alanine succinimidyl ester (I) with o-glutamine (II) by means of triethylamine in THF water gives benzyloxycarbonyl-L-alanyl-o-glutamine (III), which is esterified with bromobutane and Cs2CO3 in DMF yielding the corresponding butyl ester (IV). Deprotection of (IV) by hydrogenation with H2 over Pd/C in acetic acid affords L-alanyl-D-glutamine n-butyl ester (V), which is condensed with 1-O-benzyl-4,6-O-benzylidene-N-acetylmuramic acid (VI) bv the mixed anhydride method affording 1-O-benzyl-4,6-O-benzylidene-N-acetylmuramyl-L-alanyl-o-glutamine n-butyl ester (VII). Finally, this compound is deprotected by hydrogenation with H2 over Pd/C as before.
| 【1】 Florvall, L.; Ogren, S.O.; Potential neuroleptic agents. 2,6-dialkoxybenzamide derivatives with potent dopamine receptor blocking activities. J Med Chem 1982, 25, 11, 1280. |
| 【2】 Lefrancier, P.; Parant, M.; Audibert, F.; Chedid, L.; Choay, J.; Lederer, E. (ANVAR (Agence Natl. Valor. Rech.)); Novel compounds of the muramyl peptide. DD 145274; EP 0006068; ES 481785; FR 2428051; JP 55000392; US 4693998 . |
| 【3】 Castaner, J.; Prous, J.; Murabutide. Drugs Fut 1986, 11, 9, 750. |
| 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) | 28721 | 1-bromobutane | 109-65-9 | C4H9Br | 详情 | 详情 |
| (I) | 24665 | phenethyl 2-[(2,5-dioxo-1-pyrrolidinyl)oxy]-1-methyl-2-oxoethylcarbamate | C16H18N2O6 | 详情 | 详情 | |
| (II) | 24666 | glutamine；2,5-diamino-5-oxopentanoic acid | C5H10N2O3 | 详情 | 详情 | |
| (III) | 24667 | N(2)-(2-[[(phenethyloxy)carbonyl]amino]propanoyl)glutamine | C17H23N3O6 | 详情 | 详情 | |
| (IV) | 24668 | butyl 5-amino-5-oxo-2-[(2-[[(phenethyloxy)carbonyl]amino]propanoyl)amino]pentanoate | C21H31N3O6 | 详情 | 详情 | |
| (V) | 24669 | butyl 5-amino-2-[(2-aminopropanoyl)amino]-5-oxopentanoate | C12H23N3O4 | 详情 | 详情 | |
| (VI) | 24670 | 2-[[(8R)-7-(acetamido)-6-(benzyloxy)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy]propionic acid | 74842-55-0 | C25H29NO8 | 详情 | 详情 |
| (VII) | 24671 | butyl 2-([2-[(2-[[(8R)-7-(acetamido)-6-(benzyloxy)-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-yl]oxy]propanoyl)amino]propanoyl]amino)-5-amino-5-oxopentanoate | C37H50N4O11 | 详情 | 详情 |