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【结 构 式】 
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【分子编号】43419 【品名】methyl (2S,4S)-1-((2S)-2-[[(2S)-2-amino-4-(4-hydroxyphenyl)butanoyl]amino]-5-[[(benzyloxy)carbonyl]amino]pentanoyl)-4-azido-2-pyrrolidinecarboxylate 【CA登记号】 |
【 分 子 式 】C29H37N7O7 【 分 子 量 】595.65576 【元素组成】C 58.48% H 6.26% N 16.46% O 18.8% |
合成路线1
该中间体在本合成路线中的序号：(XI)The title compound was constructed from two tripeptide fragments. Preparation of tripeptide (XI) is shown in Scheme 29208701a. Boc-Hydroxyproline methyl ester (I) was converted to the corresponding mesylate (II), which was displaced with NaN3 in DMF to afford azide (III). Subsequent acid deprotection of the Boc group of (III) yielded 4-azidoproline methyl ester (IV). This was coupled with the protected ornithine (V) using EDC and HOBt to furnish dipeptide (VI). Further cleavage of the Boc group of (VI) using HCl in EtOAc provided (VII). After protection of homotyrosine (VIII) as the Fmoc derivative (IX), coupling with dipeptide (VII) yielded the protected tripeptide (X). The Fmoc group of (X) was then removed by treatment with diethylamine in acetonitrile, yielding tripeptide intermediate (XI).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 15780 | 1-(tert-butyl) 2-methyl (2S,4S)-4-hydroxytetrahydro-1H-pyrrole-1,2-dicarboxylate;(2S,4S)-1-tert-butyl 2-methyl 4-hydroxypyrrolidine-1,2-dicarboxylate | C11H19NO5 | 详情 | 详情 | |
| (II) | 15781 | 1-(tert-butyl) 2-methyl (2S,4R)-4-[(methylsulfonyl)oxy]tetrahydro-1H-pyrrole-1,2-dicarboxylate | C12H21NO7S | 详情 | 详情 | |
| (III) | 43411 | 1-(tert-butyl) 2-methyl (2S,4S)-4-azido-1,2-pyrrolidinedicarboxylate | C11H18N4O4 | 详情 | 详情 | |
| (IV) | 43412 | methyl (2S,4S)-4-azido-2-pyrrolidinecarboxylate | C6H10N4O2 | 详情 | 详情 | |
| (V) | 43413 | (2S)-5-[[(benzyloxy)carbonyl]amino]-2-[(tert-butoxycarbonyl)amino]pentanoic acid | 2480-93-5 | C18H26N2O6 | 详情 | 详情 |
| (VI) | 43414 | methyl (2S,4S)-4-azido-1-[(2S)-5-[[(benzyloxy)carbonyl]amino]-2-[(tert-butoxycarbonyl)amino]pentanoyl]-2-pyrrolidinecarboxylate | C24H34N6O7 | 详情 | 详情 | |
| (VII) | 43415 | methyl (2S,4S)-1-((2S)-2-amino-5-[[(benzyloxy)carbonyl]amino]pentanoyl)-4-azido-2-pyrrolidinecarboxylate | C19H26N6O5 | 详情 | 详情 | |
| (VIII) | 43416 | (2R)-2-amino-4-(4-hydroxyphenyl)butyric acid | C10H13NO3 | 详情 | 详情 | |
| (IX) | 43417 | (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-(4-hydroxyphenyl)butyric acid | C25H23NO5 | 详情 | 详情 | |
| (X) | 43418 | methyl (2S,4S)-4-azido-1-((2S)-5-[[(benzyloxy)carbonyl]amino]-2-[[(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-(4-hydroxyphenyl)butanoyl]amino]pentanoyl)-2-pyrrolidinecarboxylate | C44H47N7O9 | 详情 | 详情 | |
| (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 |
合成路线2
该中间体在本合成路线中的序号：(XI)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 |