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【结 构 式】 
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【分子编号】56121 【品名】(2S)-3-[(tert-butoxycarbonyl)amino]-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}propanoic acid 【CA登记号】 |
【 分 子 式 】C23H26N2O6 【 分 子 量 】426.46932 【元素组成】C 64.78% H 6.14% N 6.57% O 22.51% |
合成路线1
该中间体在本合成路线中的序号：(III)The protected diaminopropionic acid building block (III) was prepared as follows. Rearrangement of N-Fmoc-L-asparragine (I) upon treatment with bis(trifluoroacetoxy)phenyliodine afforded the Fmoc-diaminopropionic acid (II), which was subsequently protected at the 3-amino group with di-tert-butyl dicarbonate.
| 【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. |
| 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) | 56119 | 9-Fluorenylmethoxycarbonyl-L-asparagine; N-(9-Fluorenylmethoxycarbonyl)-L-asparagine; N-[(9H-Fluoren-9-ylmethoxy)carbonyl]-L-asparagine | 71989-16-7 | C19H18N2O5 | 详情 | 详情 |
| (II) | 56120 | Fmoc-L-diaminopropionic acid | C18H18N2O4 | 详情 | 详情 | |
| (III) | 56121 | (2S)-3-[(tert-butoxycarbonyl)amino]-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}propanoic acid | C23H26N2O6 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(III)The monocyclic peptide precursor (XVIII) was prepared by solid-phase peptide synthesis by two different sequences. In the first one, N-Fmoc-L-leucine (IV) was linked to chlorotrityl resin, and the resultant resin-bound Fmoc-leucine (V) was subsequently deprotected by treatment with piperidine in DMF. To the deprotected leucine-resin (VI) was attached the diaminopropionic acid derivative (III), using either dicyclohexylcarbodiimide or diisopropylcarbodiimide as the coupling reagents, to yield the dipeptide resin (VII), which was further deprotected to (VIII) by means of piperidine in DMF.
| 【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 |
|---|---|---|---|---|---|---|
| (IV),(V) | 19934 | (2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-4-methylpentanoic acid | C21H23NO4 | 详情 | 详情 | |
| (III) | 56121 | (2S)-3-[(tert-butoxycarbonyl)amino]-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}propanoic acid | C23H26N2O6 | 详情 | 详情 | |
| (VI) | 26057 | L-Leucine | 61-90-5 | C6H13NO2 | 详情 | 详情 |
| (VII) | 56122 | (2S)-2-[((2S)-3-[(tert-butoxycarbonyl)amino]-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}propanoyl)amino]-4-methylpentanoic acid | C29H37N3O7 | 详情 | 详情 | |
| (VIII) | 56123 | (2S)-2-({(2S)-2-amino-3-[(tert-butoxycarbonyl)amino]propanoyl}amino)-4-methylpentanoic acid | C14H27N3O5 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(III)Another route for the synthesis of intermediate (XVIII) has also been described: To resin (XXVI) was coupled N-Fmoc-L-leucine (IV) to afford resin (XXVII), after Fmoc deprotection with piperidine. Subsequent coupling with the protected diaminopropionic acid (III), followed by a new deprotection with piperidine, gave the resin-bound linear peptide (XXVIII). After trifluoroacetic acid-promoted cleavage from the resin, the resultant side-chain-protected peptide was cyclized to (XVIII)
| 【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. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (III) | 56121 | (2S)-3-[(tert-butoxycarbonyl)amino]-2-{[(9H-fluoren-9-ylmethoxy)carbonyl]amino}propanoic acid | C23H26N2O6 | 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 | |
| (XXVI) | 56136 | (2S)-2-{[(2S)-2-{[(2S)-2-{[(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}-4-(tert-butoxy)-4-oxobutanoyl]amino}-3-(1H-indol-3-yl)propanoyl]amino}-3-phenylpropanoic acid | C46H59N7O16 | 详情 | 详情 | |
| (XXVII) | 56137 | (2S,5S,8S,11S,14S)-11-[2-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-oxoethyl]-14-amino-2-benzyl-8-[2-(tert-butoxy)-2-oxoethyl]-5-(1H-indol-3-ylmethyl)-16-methyl-4,7,10,13-tetraoxo-3,6,9,12-tetraazaheptadecan-1-oic acid | C52H70N8O17 | 详情 | 详情 | |
| (XXVIII) | 56138 | (7S,10S,13S,16S,19S,22S)-13-[2-({(2R,3R,4R,5R,6R)-3-(acetylamino)-4,5-bis(acetyloxy)-6-[(acetyloxy)methyl]tetrahydro-2H-pyran-2-yl}amino)-2-oxoethyl]-7-amino-22-benzyl-16-[2-(tert-butoxy)-2-oxoethyl]-19-(1H-indol-3-ylmethyl)-10-isobutyl-2,2-dimethyl-4,8,11,14,17,20-hexaoxo-3-oxa-5,9,12,15,18,21-hexaazatricosan-23-oic acid | C60H84N10O20 | 详情 | 详情 |