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【结 构 式】 
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【分子编号】56131 【品名】2-[(2S,5S,8S,11S,14S,17S)-17-[2-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-oxoethyl]-11-(aminomethyl)-8-benzyl-5-(1H-indol-3-ylmethyl)-14-isobutyl-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexaazacyclooctadecan-2-yl]acetic acid 【CA登记号】 |
【 分 子 式 】C51H66N10O17 【 分 子 量 】1091.14224 【元素组成】C 56.14% H 6.1% N 12.84% O 24.93% |
合成路线1
该中间体在本合成路线中的序号：(XIX)The linear precursor resin (XVI) was cleaved by means of trifluoroacetic acid yielding the side-chain protected peptide (XVII). Cyclization of (XVII) to furnish the monocyclic peptide (XVIII) was effected by treatment either with PyBOP or with 2-chloro-1,3-dimethyl-2-imidazolinium hexafluorophosphate (CIP) in the presence of HOAt. The side-chain-protecting groups were then cleaved by treatment with trifluoroacetic acid to give (XIX).
| 【1】 Aimoto, S.; Akaji, K.; Synthesis of MEN11420, a glycosylated bicyclic peptide, by intramolecular double cyclization using a chloroimidazolinium coupling reagent. Tetrahedron 2001, 57, 9, 1749. |
| 【2】 Arcamone, F.; Maggi, C.A.; Quartara, L.; Giannotti, D. (Menarini Industrie Farma Riunite Srl); Bicyclic tachykinins antagonists, preparation thereof and their use in pharmaceutical compsn.. JP 1999501643; WO 9628467 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVI),(XVII) | 56128 | (2S,5S,8S,11S,14S)-14-{[(2S)-4-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-amino-4-oxobutanoyl]amino}-8-benzyl-5-{[(tert-butoxycarbonyl)amino]methyl}-11-(1H-indol-3-ylmethyl)-2-isobutyl-18,18-dimethyl-4,7,10,13,16-pentaoxo-17-oxa-3,6,9,12-tetraazanonadecan-1-oic acid | C60H84N10O20 | 详情 | 详情 | |
| (XVIII) | 56130 | tert-butyl 2-[(2S,5S,8S,11S,14S,17S)-17-[2-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-oxoethyl]-8-benzyl-11-{[(tert-butoxycarbonyl)amino]methyl}-5-(1H-indol-3-ylmethyl)-14-isobutyl-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexaazacyclooctadecan-2-yl]acetate | C60H82N10O19 | 详情 | 详情 | |
| (XIX) | 56131 | 2-[(2S,5S,8S,11S,14S,17S)-17-[2-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-oxoethyl]-11-(aminomethyl)-8-benzyl-5-(1H-indol-3-ylmethyl)-14-isobutyl-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexaazacyclooctadecan-2-yl]acetic acid | C51H66N10O17 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIX)Condensation between the side-chain amino and carboxy groups of (XIX) to produce the bicyclic peptide (XX) was accomplished by treatment with either PyBOP or CIP reagents. The acetate ester groups of (XX) were finally removed by alcoholysis with methanolic NaOMe yielding the title compound.
| 【1】 Aimoto, S.; Akaji, K.; Synthesis of MEN11420, a glycosylated bicyclic peptide, by intramolecular double cyclization using a chloroimidazolinium coupling reagent. Tetrahedron 2001, 57, 9, 1749. |
| 【2】 Arcamone, F.; Maggi, C.A.; Quartara, L.; Giannotti, D. (Menarini Industrie Farma Riunite Srl); Bicyclic tachykinins antagonists, preparation thereof and their use in pharmaceutical compsn.. JP 1999501643; WO 9628467 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIX) | 56131 | 2-[(2S,5S,8S,11S,14S,17S)-17-[2-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-oxoethyl]-11-(aminomethyl)-8-benzyl-5-(1H-indol-3-ylmethyl)-14-isobutyl-3,6,9,12,15,18-hexaoxo-1,4,7,10,13,16-hexaazacyclooctadecan-2-yl]acetic acid | C51H66N10O17 | 详情 | 详情 | |
| (XX) | 56132 | (2R,3R,4R,5R,6R)-3-(acetylamino)-5-(acetyloxy)-6-[(acetyloxy)methyl]-2-({2-[(1S,4S,7S,10S,13S,16S)-4-benzyl-7-(1H-indol-3-ylmethyl)-16-isobutyl-3,6,9,12,15,18,21-heptaoxo-2,5,8,11,14,17,20-heptaazabicyclo[8.8.4]docos-13-yl]acetyl}amino)tetrahydro-2H-pyran-4-yl acetate | C51H64N10O16 | 详情 | 详情 |