【结 构 式】 |
【分子编号】65161 【品名】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 【CA登记号】 |
【 分 子 式 】C47H59N5O7 【 分 子 量 】806.01496 【元素组成】C 70.04% H 7.38% N 8.69% O 13.9% |
合成路线1
该中间体在本合成路线中的序号:(XVI)In a similar fashion, N-Boc-L-phenylalanine (XI) is coupled with L-valine benzyl ester (XIII) to furnish the protected dipeptide (XIV). Debenzylation of (XIV) with H2 and Pd/C leads to acid (XV), which is then condensed with tripeptide (XII) to yield, after deprotection with formic acid, the pentapeptide derivative (XVI).
【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 |
---|---|---|---|---|---|---|
(XI) | 12874 | (2R)-2-[(tert-Butoxycarbonyl)amino]-3-phenylpropionic acid; N-alpha-t-BOC-L-Phenylalanine | 13734-34-4 | C14H19NO4 | 详情 | 详情 |
(XII) | 65159 | benzyl (2S)-2-{[(2S,3R)-2-{[(2S)-2-amino-3-phenylpropanoyl]amino}-3-(benzyloxy)butanoyl]amino}-4-methylpentanoate | C33H41N3O5 | 详情 | 详情 | |
(XIII) | 41936 | benzyl (2S)-2-amino-3-methylbutanoate | C12H17NO2 | 详情 | 详情 | |
(XIV) | 65162 | benzyl (2S)-2-({(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoyl}amino)-3-methylbutanoate | C26H34N2O5 | 详情 | 详情 | |
(XV) | 65163 | (2S)-2-({(2S)-2-[(tert-butoxycarbonyl)amino]-3-phenylpropanoyl}amino)-3-methylbutanoic acid | C19H28N2O5 | 详情 | 详情 | |
(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 |
合成路线2
该中间体在本合成路线中的序号:(XVI)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 |