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【结 构 式】 
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【分子编号】39391 【品名】(2S)-2-[(tert-butoxycarbonyl)amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid 【CA登记号】 |
【 分 子 式 】C18H28N4O6S 【 分 子 量 】428.50968 【元素组成】C 50.45% H 6.59% N 13.07% O 22.4% S 7.48% |
合成路线1
该中间体在本合成路线中的序号：(XXIX)Peptide resin (XX) was subjected to sequential coupling-deprotection cycles with the following amino acids: N-Boc-(2-thienyl)alanine (XXI), N-Boc-glycine (XXIII), N-Boc-4-hydroxyproline (XXV), N-Boc-proline (XXVII), Nalpha-Boc-NG-tosyl-arginine (XXIX) and Nalpha-Boc-NG-nitro-D-arginine (XXXI) to produce peptide resins (XXII), (XXIV), (XXVI), (XXVIII), (XXX) and (XXXII), respectively. The title peptide was finally obtained by deprotection and cleavage from the resin by means of treatment with HF.
| 【1】 Daffix, I.; Bergé, G.; Amblard, M.; et al.; Synthesis and characterization of bradykinin B2 receptor agonists containing constrained dipeptide mimics. J Med Chem 1999, 42, 20, 4193. |
| 【2】 Dodey, P.; Luccarini, J.-M.; Martinez, J.; Amblard, M.; Daffix, I. (Fournier Industrie et Santé); Peptides agonists of bradykinine B2 receptor. FR 2756566; WO 9824809 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XXVIII) | 39388 | C54H67N11O13S3 | 详情 | 详情 | ||
| (XXIX) | 39391 | (2S)-2-[(tert-butoxycarbonyl)amino]-5-[(imino[[(4-methylphenyl)sulfonyl]amino]methyl)amino]pentanoic acid | C18H28N4O6S | 详情 | 详情 | |
| (XXX) | 39389 | C67H85N15O16S4 | 详情 | 详情 | ||
| (XXXI) | 32085 | N(G)-nitro-N2-(tert-butoxy-carbonyl)-L-arginine; Nalpha-(tert-butoxycarbonyl)-Nomega-nitro-L-arginine | C11H21N5O6 | 详情 | 详情 | |
| (XXXII) | 39390 | C73H96N20O19S4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)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 |