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【结 构 式】 
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【分子编号】58837 【品名】methyl 2-{[(2S)-2-{[(2S)-2-{[(2-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,3-thiazol-4-yl)carbonyl]amino}-3-(1H-indol-3-yl)propanoyl]amino}-3-(4-methoxy-1H-indol-3-yl)propanoyl]amino}acetate 【CA登记号】 |
【 分 子 式 】C37H43N7O8S 【 分 子 量 】745.8568 【元素组成】C 59.58% H 5.81% N 13.15% O 17.16% S 4.3% |
合成路线1
该中间体在本合成路线中的序号：(XVIII)N-Boc-D-Alanine (XI) is converted to the corresponding amide (XII) by reaction with ammonia in the presence of EDC and HOBt. Subsequent treatment of (XII) with Belleau's reagent (2,4-bis(4-phenoxyphenyl)-1,3,2,4-dithiaphosphetane-2,4-disulfide) furnishes thioamide (XIII). S-Alkylation of thioamide (XIII) with ethyl bromopyruvate (XIV) gives intermediate (XV), which is cyclized to thiazole (XVI) upon treatment with trifluoroacetic anhydride and 2,6-lutidine. After saponification of the ester group of (XVI) with LiOH, the resultant acid (XVII) is coupled with tripeptide (X) to provide precursor (XVIII).
| 【1】 Ley, S.V.; et al.; Total synthesis of the cyclic heptapeptide argyrin B: A new potent inhibitor of T-cell independent antibody formation. Org Lett 2002, 4, 5, 711. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 58834 | methyl 2-{[(2S)-2-{[(2S)-2-amino-3-(1H-indol-3-yl)propanoyl]amino}-3-(4-methoxy-1H-indol-3-yl)propanoyl]amino}acetate | C26H29N5O5 | 详情 | 详情 | |
| (XI) | 15859 | Boc-D-Alanine; (2R)-2-[(tert-butoxycarbonyl)amino]propionic acid | 7764-95-6 | C8H15NO4 | 详情 | 详情 |
| (XII) | 46750 | tert-butyl (1R)-2-amino-1-methyl-2-oxoethylcarbamate | C8H16N2O3 | 详情 | 详情 | |
| (XIII) | 48364 | tert-butyl (1R)-2-amino-1-methyl-2-thioxoethylcarbamate | C8H16N2O2S | 详情 | 详情 | |
| (XIV) | 25183 | ethyl 3-bromo-2-oxopropanoate;ethyl 3-bromopyruvate;Bromopyruvic acid ethyl ester;ethyl 3-bromopyruvate;ethyl bromopyruvate | 70-23-5 | C5H7BrO3 | 详情 | 详情 |
| (XV) | 58835 | ethyl 3-({(2R)-2-[(tert-butoxycarbonyl)amino]propanimidoyl}sulfanyl)-2-oxopropanoate | C13H22N2O5S | 详情 | 详情 | |
| (XVI) | 48366 | ethyl 2-[(1R)-1-[(tert-butoxycarbonyl)amino]ethyl]-1,3-thiazole-4-carboxylate | C13H20N2O4S | 详情 | 详情 | |
| (XVII) | 58836 | 2-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,3-thiazole-4-carboxylic acid | C11H16N2O4S | 详情 | 详情 | |
| (XVIII) | 58837 | methyl 2-{[(2S)-2-{[(2S)-2-{[(2-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,3-thiazol-4-yl)carbonyl]amino}-3-(1H-indol-3-yl)propanoyl]amino}-3-(4-methoxy-1H-indol-3-yl)propanoyl]amino}acetate | C37H43N7O8S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVIII)Basic hydrolysis of the precursor tetrapeptide ester (XVIII) provides acid (XXVIII). This is then coupled to the tripeptide ester (XXVII), leading to the linear peptide precursor (XXIX). Sequential hydrolysis in (XXIX) of the ethyl ester group with LiOH and the N-Boc group with trifluoroacetic acid produces aminoacid (XXX).
| 【1】 Ley, S.V.; et al.; Total synthesis of the cyclic heptapeptide argyrin B: A new potent inhibitor of T-cell independent antibody formation. Org Lett 2002, 4, 5, 711. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XVIII) | 58837 | methyl 2-{[(2S)-2-{[(2S)-2-{[(2-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,3-thiazol-4-yl)carbonyl]amino}-3-(1H-indol-3-yl)propanoyl]amino}-3-(4-methoxy-1H-indol-3-yl)propanoyl]amino}acetate | C37H43N7O8S | 详情 | 详情 | |
| (XXVII) | 58844 | ethyl 2-[[(2R)-2-{[(2R)-2-aminobutanoyl]amino}-3-(phenylselanyl)propanoyl](methyl)amino]acetate | C18H27N3O4Se | 详情 | 详情 | |
| (XXVIII) | 58845 | 2-{[(2S)-2-{[(2S)-2-{[(2-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,3-thiazol-4-yl)carbonyl]amino}-3-(1H-indol-3-yl)propanoyl]amino}-3-(4-methoxy-1H-indol-3-yl)propanoyl]amino}acetic acid | C36H41N7O8S | 详情 | 详情 | |
| (XXIX) | 58846 | ethyl (3S,6S,12R,15R)-1-(2-{(1R)-1-[(tert-butoxycarbonyl)amino]ethyl}-1,3-thiazol-4-yl)-12-ethyl-3-(1H-indol-3-ylmethyl)-6-[(4-methoxy-1H-indol-3-yl)methyl]-17-methyl-1,4,7,10,13,16-hexaoxo-15-[(phenylselanyl)methyl]-2,5,8,11,14,17-hexaazanonadecan-19-oate | C54H66N10O11SSe | 详情 | 详情 | |
| (XXX) | 58847 | (3S,6S,12R,15R)-1-{2-[(1R)-1-aminoethyl]-1,3-thiazol-4-yl}-12-ethyl-3-(1H-indol-3-ylmethyl)-6-[(4-methoxy-1H-indol-3-yl)methyl]-17-methyl-1,4,7,10,13,16-hexaoxo-15-[(phenylselanyl)methyl]-2,5,8,11,14,17-hexaazanonadecan-19-oic acid | C47H54N10O9SSe | 详情 | 详情 |