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【结 构 式】 
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【药物名称】[Dmt1]DALDA, SUPER-DALDA 【化学名称】2,6-Dimethyl-L-tyrosyl-D-arginyl-L-phenylalanyl-L-lysinamide 【CA登记号】 【 分 子 式 】C32H49N9O5 【 分 子 量 】639.80463 |
【开发单位】AstraZeneca (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Opioid Analgesics, mu-Opioid Agonists |
合成路线1
The title peptide was prepared by solid-phase synthesis using a p-methylbenzhydrylamine resin (II). Coupling of Boc-lysine(2-ClZ) (I) to the resin (II) using diisopropylcarbodiimide (DIC) and 1-hydroxybenzotriazole (HOBt) afforded the amide resin (III). The N-Boc group was then selectively deprotected with trifluoroacetic acid in CH2Cl2, yielding resin (IV). To this were sequentially attached the protected amino acids: Boc-phenylalanine (V), Boc-D-arginine(Ts) (VII) and Boc-2',6'-dimethyltyrosine(Boc) (IX) employing DIC/HOBt and then Boc deprotection with trifluoroacetic acid to provide the peptide resins (VI), (VIII) and (X), respectively. Finally, the desired peptide amide was deprotected and cleaved from the resin (X) by treatment with HF and anisole.
| 【1】 Nguyen, T.M.-D.; Dupuis, S.; Chung, N.N.; Schiller, P.W.; Berezowska, I.; Lemieux, C.; Weltrowska, G.; Synthesis and in vitro opioid activity profiles of DALDA analogues. Eur J Med Chem 2000, 35, 10, 895. |
| 【2】 Schiller, P. (AstraZeneca AB); DALDA analogs and their use. WO 0055189 . |
| 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) | 31374 | (2S)-2-[(tert-butoxycarbonyl)amino]-6-([[(2-chlorobenzyl)oxy]carbonyl]amino)hexanoic acid | C19H27ClN2O6 | 详情 | 详情 | |
| (III) | 45666 | 2-chlorobenzyl (5S)-6-amino-5-[(tert-butoxycarbonyl)amino]-6-oxohexylcarbamate | C19H28ClN3O5 | 详情 | 详情 | |
| (IV) | 45669 | 2-chlorobenzyl (5S)-5,6-diamino-6-oxohexylcarbamate | C14H20ClN3O3 | 详情 | 详情 | |
| (V) | 12874 | (2R)-2-[(tert-Butoxycarbonyl)amino]-3-phenylpropionic acid; N-alpha-t-BOC-L-Phenylalanine | 13734-34-4 | C14H19NO4 | 详情 | 详情 |
| (VI) | 45667 | 2-chlorobenzyl (5S)-6-amino-5-[[(2S)-2-amino-3-phenylpropanoyl]amino]-6-oxohexylcarbamate | C23H29ClN4O4 | 详情 | 详情 | |
| (VII) | 39391 | (2S)-2-[(tert-butoxycarbonyl)amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid | C18H28N4O6S | 详情 | 详情 | |
| (VIII) | 45668 | 2-chlorobenzyl (5S)-6-amino-5-[[(2S)-2-([(2R)-2-amino-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoyl]amino)-3-phenylpropanoyl]amino]-6-oxohexylcarbamate | C36H47ClN8O7S | 详情 | 详情 | |
| (IX) | 40876 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-[4-[(tert-butoxycarbonyl)oxy]-2,6-dimethylphenyl]propionic acid | C21H31NO7 | 详情 | 详情 | |
| (X) | 45670 | 2-chlorobenzyl (5S)-6-amino-5-[[(2S)-2-([(2R)-2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoyl]amino)-3-phenylpropanoyl]amino]-6-oxohexylcarbamate | C47H60ClN9O9S | 详情 | 详情 |