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【结 构 式】 
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【分子编号】43425 【品名】(2S)-1-[(2S,3R)-2-[((2S)-2-[(tert-butoxycarbonyl)amino]-5-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanoyl)amino]-3-hydroxybutanoyl]-2-pyrrolidinecarboxylic acid 【CA登记号】 |
【 分 子 式 】C34H44N4O9 【 分 子 量 】652.74492 【元素组成】C 62.56% H 6.79% N 8.58% O 22.06% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)For the preparation of tripeptide intermediate (XVIII), N-Cbz-threonine (XII) was coupled with proline benzyl ester (XIII) to give dipeptide (XIV). Subsequent hydrogenolysis of the benzyl groups of (XIV) in the presence of Pd/C furnished threonyl proline (XV). Coupling of (XV) with the succinimidyl ester (XVII) prepared from the protected ornithine (XVI) then provided tripeptide intermediate (XVIII).
| 【1】 Chen, H.-J.; Klein, L.L.; Li, L.; et al.; Total synthesis and antifungal evaluation of cyclic aminohexapeptides. Bioorg Med Chem Lett 2000, 8, 7, 1677. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XII) | 43420 | (2S,3R)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxybutyric acid | 19728-63-3 | C12H15NO5 | 详情 | 详情 |
| (XIII) | 20930 | benzyl (2S)-2-pyrrolidinecarboxylate | 16652-71-4 | C12H15NO2 | 详情 | 详情 |
| (XIV) | 43421 | benzyl (2S)-1-((2S,3R)-2-[[(benzyloxy)carbonyl]amino]-3-hydroxybutanoyl)-2-pyrrolidinecarboxylate | C24H28N2O6 | 详情 | 详情 | |
| (XV) | 43422 | (2S)-1-[(2S,3R)-2-amino-3-hydroxybutanoyl]-2-pyrrolidinecarboxylic acid | C9H16N2O4 | 详情 | 详情 | |
| (XVI) | 43423 | (2S)-2-[(tert-butoxycarbonyl)amino]-5-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanoic acid | C25H30N2O6 | 详情 | 详情 | |
| (XVII) | 43424 | 9H-fluoren-9-ylmethyl (4S)-4-[(tert-butoxycarbonyl)amino]-5-[(2,5-dioxo-1-pyrrolidinyl)oxy]-5-oxopentylcarbamate | C29H33N3O8 | 详情 | 详情 | |
| (XVIII) | 43425 | (2S)-1-[(2S,3R)-2-[((2S)-2-[(tert-butoxycarbonyl)amino]-5-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanoyl)amino]-3-hydroxybutanoyl]-2-pyrrolidinecarboxylic acid | C34H44N4O9 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVIII)EEDQ-mediated coupling between tripeptides (XI) and (XVIII) furnished the linear hexapeptide (XIX). After deprotection of (XIX) with NaOH, cyclization using DPPA produced the cyclic peptide (XX). The Boc protecting group of (XX) was then removed by means of trifluoroacetic acid, and the resulting amine was acylated with the trichlorophenyl active ester (XXI) to give amide (XXII).
| 【1】 Chen, H.-J.; Klein, L.L.; Li, L.; et al.; Total synthesis and antifungal evaluation of cyclic aminohexapeptides. Bioorg Med Chem Lett 2000, 8, 7, 1677. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XI) | 43419 | methyl (2S,4S)-1-((2S)-2-[[(2S)-2-amino-4-(4-hydroxyphenyl)butanoyl]amino]-5-[[(benzyloxy)carbonyl]amino]pentanoyl)-4-azido-2-pyrrolidinecarboxylate | C29H37N7O7 | 详情 | 详情 | |
| (XVIII) | 43425 | (2S)-1-[(2S,3R)-2-[((2S)-2-[(tert-butoxycarbonyl)amino]-5-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanoyl)amino]-3-hydroxybutanoyl]-2-pyrrolidinecarboxylic acid | C34H44N4O9 | 详情 | 详情 | |
| (XIX) | 43426 | methyl (2S,4S)-4-azido-1-((2S)-5-[[(benzyloxy)carbonyl]amino]-2-[[(2S)-2-[[((2S)-1-[(2S,3R)-2-[((2S)-2-[(tert-butoxycarbonyl)amino]-5-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]pentanoyl)amino]-3-hydroxybutanoyl]pyrrolidinyl)carbonyl]amino]-4-(4-hydro | C63H79N11O15 | 详情 | 详情 | |
| (XX) | 43427 | tert-butyl (6S,9S,14aS,16S,20S,23S,25aS)-16-azido-20-(3-[[(benzyloxy)carbonyl]amino]propyl)-6-[(1R)-1-hydroxyethyl]-23-(4-hydroxyphenethyl)-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohenicosin-9-ylcarb | C47H65N11O12 | 详情 | 详情 | |
| (XXI) | 43428 | 2,4,5-trichlorophenyl 4-[4-[4-(octyloxy)phenyl]-1-piperazinyl]benzoate | C31H35Cl3N2O3 | 详情 | 详情 | |
| (XXII) | 43429 | benzyl 3-[(6S,9S,14aS,16S,20S,23S,25aS)-16-azido-6-[(1R)-1-hydroxyethyl]-23-(4-hydroxyphenethyl)-9-[(4-[4-[4-(octyloxy)phenyl]-1-piperazinyl]benzoyl)amino]-5,8,14,19,22,25-hexaoxotetracosahydro-1H-dipyrrolo[2,1-c:2,1-l][1,4,7,10,13,16]hexaazacyclohe | C67H89N13O12 | 详情 | 详情 |