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【结 构 式】 
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【分子编号】65164 【品名】(2S,5S,8S,11S,14S,20S,23S,24S)-23-amino-8,14-dibenzyl-5-[(1R)-1-hydroxyethyl]-2,20-diisobutyl-11-isopropyl-24-methyl-4,7,10,13,16,19,22-heptaoxo-3,6,9,12,15,18,21-heptaazahexacosan-1-oic acid 【CA登记号】 |
【 分 子 式 】C47H72N8O10 【 分 子 量 】909.1366 【元素组成】C 62.09% H 7.98% N 12.33% O 17.6% |
合成路线1
该中间体在本合成路线中的序号：(XXIII)Coupling of N-Boc-L-leucine (XVII) with glycine benzyl ester (XVIII), followed by acidic N-Boc group cleavage, affords the dipeptide benzyl ester (XIX), which is submitted to coupling with N-Boc-L-isoleucine (XX) and further benzyl ester hydrogenolysis to give rise to the N-Boc tripeptide (XXI). Then, assembly between (XXI) and pentapeptide (XVI) is accomplished by means of EDC/HOBt, providing the protected peptide (XXII). Hydrogenolysis of the benzyl groups of (XXII), followed by Boc group cleavage with trifluoroacetic acid, leads to the fully deprotected octapeptide (XXIII).
| 【1】 Rawale, S.; Hrihorczuk, L.M.; Wei, W.-Z.; Zemlicka, J.; Synthesis and biological activity of the prodrug of class I major histocompatibility peptide GILGFVFTL activated by Beta-glucuronidase. J Med Chem 2002, 45, 4, 937. |
| 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) | 65161 | benzyl (2S,5S,8S,11S,14S)-14-amino-8-benzyl-5-[(1R)-1-(benzyloxy)ethyl]-2-isobutyl-11-isopropyl-4,7,10,13-tetraoxo-15-phenyl-3,6,9,12-tetraazapentadecan-1-oate | C47H59N5O7 | 详情 | 详情 | |
| (XVII) | 23663 | (2S)-2-[(tert-butoxycarbonyl)amino]-4-methylpentanoic acid；N-Boc-L-leucine | C11H21NO4 | 详情 | 详情 | |
| (XVIII) | 13601 | benzyl 2-aminoacetate; Glycine benzyl ester hydrochloride | 1738-68-7 | C9H11NO2 | 详情 | 详情 |
| (XIX) | 65167 | benzyl 2-{[(2S)-2-amino-4-methylpentanoyl]amino}acetate | C15H22N2O3 | 详情 | 详情 | |
| (XX) | 30009 | (2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-methylpentanoic acid | 13139-16-7 | C11H21NO4 | 详情 | 详情 |
| (XXI) | 65166 | (6S,9S)-9-isobutyl-2,2-dimethyl-6-[(1S)-1-methylpropyl]-4,7,10-trioxo-3-oxa-5,8,11-triazatridecan-13-oic acid | C19H35N3O6 | 详情 | 详情 | |
| (XXII) | 65165 | benzyl (6S,9S,15S,18S,21S,24S,27S)-15,21-dibenzyl-24-[(1R)-1-(benzyloxy)ethyl]-9,27-diisobutyl-18-isopropyl-2,2-dimethyl-6-[(1S)-1-methylpropyl]-4,7,10,13,16,19,22,25-octaoxo-3-oxa-5,8,11,14,17,20,23,26-octaazaoctacosan-28-oate | C66H92N8O12 | 详情 | 详情 | |
| (XXIII) | 65164 | (2S,5S,8S,11S,14S,20S,23S,24S)-23-amino-8,14-dibenzyl-5-[(1R)-1-hydroxyethyl]-2,20-diisobutyl-11-isopropyl-24-methyl-4,7,10,13,16,19,22-heptaoxo-3,6,9,12,15,18,21-heptaazahexacosan-1-oic acid | C47H72N8O10 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIII)Condensation of pentafluorophenyl ester (VI) with octapeptide (XXIII) gives rise to the nonapeptide conjugate (XXIV). The methyl ester group of (XXIV) is finally hydrolyzed by means of barium hydroxide in MeOH to produce the target compound.
| 【1】 Rawale, S.; Hrihorczuk, L.M.; Wei, W.-Z.; Zemlicka, J.; Synthesis and biological activity of the prodrug of class I major histocompatibility peptide GILGFVFTL activated by Beta-glucuronidase. J Med Chem 2002, 45, 4, 937. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 65157 | methyl (2S,3S,4S,5R,6S)-3,4,5-trihydroxy-6-(2-nitro-4-{[({[2-oxo-2-(2,3,4,5,6-pentafluorophenoxy)ethyl]amino}carbonyl)oxy]methyl}phenoxy)tetrahydro-2H-pyran-2-carboxylate | C23H19F5N2O13 | 详情 | 详情 | |
| (XXIII) | 65164 | (2S,5S,8S,11S,14S,20S,23S,24S)-23-amino-8,14-dibenzyl-5-[(1R)-1-hydroxyethyl]-2,20-diisobutyl-11-isopropyl-24-methyl-4,7,10,13,16,19,22-heptaoxo-3,6,9,12,15,18,21-heptaazahexacosan-1-oic acid | C47H72N8O10 | 详情 | 详情 | |
| (XXIV) | 65168 | (8S,11S,17S,20S,23S,26S,29S)-17,23-dibenzyl-26-[(1R)-1-hydroxyethyl]-11,29-diisobutyl-20-isopropyl-8-[(1S)-1-methylpropyl]-1-(3-nitro-4-{[(2S,3R,4S,5S,6S)-3,4,5-trihydroxy-6-(methoxycarbonyl)tetrahydro-2H-pyran-2-yl]oxy}phenyl)-3,6,9,12,15,18,21,24, | C64H90N10O22 | 详情 | 详情 |