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【结 构 式】 
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【分子编号】42846 【品名】tert-butyl (5R,8R)-5-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-8-[4-[(tert-butoxycarbonyl)amino]butyl]-17-imino-7 【CA登记号】 |
【 分 子 式 】C67H114N14O15S2 【 分 子 量 】1419.85952 【元素组成】C 56.68% H 8.09% N 13.81% O 16.9% S 4.52% |
合成路线1
该中间体在本合成路线中的序号：(IX)The title compound was prepared by solid-phase peptide synthesis starting from N-Fmoc-D-proline linked to Rink resin (I). Deprotection of the Fmoc group by means of piperidine in DMA afforded proline-resin (II). Coupling of N-alpha-Fmoc-NG-Pmc-D-arginine (III) to proline-resin (II) using diisopropyl carbodiimide (DIC) and HOBt, followed by Fmoc deprotection with piperidine in DMA, furnished dipeptide-resin (IV). Further coupling and deprotection cycles incorporating the amino acid N2-Fmoc-N6-Boc-D-lysine (V) (twice) and the peptoid residue N-Fmoc-N-[3-(3-Pmc-guanidino)propyl]glycine (VIII) yielded the peptide resins (VI), (VII) and (IX), respectively.
| 【1】 Hamy, F.; et al.; An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication. Proceedings of the National Academy of Sciences of the United States of America 1997, 94, 8, 3548. |
| 【2】 Felder, E.; Hamy, F.; Heizmann, G.; Klimkait, T.; Lazdins, J.K. (Novartis AG); Antiviral peptoid cpds.. EP 0832110; WO 9640759 . |
| 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) | 42841 | 9H-fluoren-9-ylmethyl (2R)-2-(aminocarbonyl)-1-pyrrolidinecarboxylate | C20H20N2O3 | 详情 | 详情 | |
| (II) | 37077 | (2R)-2-pyrrolidinecarboxamide | C5H10N2O | 详情 | 详情 | |
| (III) | 19035 | (2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4-dihydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoic acid | 119831-72-0 | C35H42N4O7S | 详情 | 详情 |
| (IV) | 42842 | (2R)-1-[(2R)-2-amino-5-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]pentanoyl]-2-pyrrolidinecarboxamide | C25H42N6O5S | 详情 | 详情 | |
| (V) | 42847 | (2R)-6-[(tert-butoxycarbonyl)amino]-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]hexanoic acid | C26H32N2O6 | 详情 | 详情 | |
| (VI) | 42843 | tert-butyl (5R)-5-amino-6-([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)-6-oxohexylcarbamate | C36H62N8O8S | 详情 | 详情 | |
| (VII) | 42844 | tert-butyl (5R)-5-amino-6-([(1R)-1-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-5-[(tert-butoxycarbonyl)amino]pentyl | C47H82N10O11S | 详情 | 详情 | |
| (VIII) | 42845 | 2-([(9H-fluoren-9-ylmethoxy)carbonyl][3-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]propyl]amino)acetic acid | C35H44N4O7S | 详情 | 详情 | |
| (IX) | 42846 | tert-butyl (5R,8R)-5-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-8-[4-[(tert-butoxycarbonyl)amino]butyl]-17-imino-7 | C67H114N14O15S2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Further coupling and deprotection cycles incorporating peptoid N-Fmoc-N-benzylglycine (X), and twice peptoid (VIII), yielded the peptoid-resins (XI) and (XII), respectively. Bromoacetic acid (XIII) was subsequently coupled to resin (XII) to afford the bromoacetamido peptoid-resin (XIV).
| 【1】 Hamy, F.; et al.; An inhibitor of the Tat/TAR RNA interaction that effectively suppresses HIV-1 replication. Proceedings of the National Academy of Sciences of the United States of America 1997, 94, 8, 3548. |
| 【2】 Felder, E.; Hamy, F.; Heizmann, G.; Klimkait, T.; Lazdins, J.K. (Novartis AG); Antiviral peptoid cpds.. EP 0832110; WO 9640759 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VIII) | 42845 | 2-([(9H-fluoren-9-ylmethoxy)carbonyl][3-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]propyl]amino)acetic acid | C35H44N4O7S | 详情 | 详情 | |
| (IX) | 42846 | tert-butyl (5R,8R)-5-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-8-[4-[(tert-butoxycarbonyl)amino]butyl]-17-imino-7 | C67H114N14O15S2 | 详情 | 详情 | |
| (X) | 42848 | 2-[benzyl[(9H-fluoren-9-ylmethoxy)carbonyl]amino]acetic acid | C24H21NO4 | 详情 | 详情 | |
| (XI) | 42849 | tert-butyl (5R,8R)-5-[([(1R)-1-[[(2R)-2-(aminocarbonyl)pyrrolidinyl]carbonyl]-4-[(imino[[(2,2,5,7,8-pentamethyl-3,4,4a,8a-tetrahydro-2H-chromen-6-yl)sulfonyl]amino]methyl)amino]butyl]amino)carbonyl]-12-[2-(benzylamino)acetyl]-8-[4-[(tert-butoxycarbo | C76H123N15O16S2 | 详情 | 详情 | |
| (XII) | 42850 | C116H187N23O24S4 | 详情 | 详情 | ||
| (XIII) | 23660 | 2-Bromoacetic acid | 79-08-3 | C2H3BrO2 | 详情 | 详情 |
| (XIV) | 42851 | C118H188BrN23O25S4 | 详情 | 详情 |