|
【结 构 式】 
|
【分子编号】58834 【品名】methyl 2-{[(2S)-2-{[(2S)-2-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 】C26H29N5O5 【 分 子 量 】491.54696 【元素组成】C 63.53% H 5.95% N 14.25% O 16.27% |
合成路线1
该中间体在本合成路线中的序号：(X)The racemic 4-methoxytryptophan amide (I) is resolved using immobilized Penicillin G acylase, to afford the desired L-aminoacid (III), while leaving unaltered the enantiomeric D-amide (II). After protection of aminoacid (III) as the N-benzyloxycarbonyl derivative (IV), coupling with glycine methyl ester (V) gives dipeptide (VI). Hydrogenolysis of the benzyloxycarbonyl protecting group of (VI) yields amine (VII), which is then coupled with N-Cbz-L-tryptophan (VIII) to produce the protected tripeptide (IX). Hydrogenolysis of (IX) in the presence of Pd/C provides the tripeptide building block (X).
| 【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 |
|---|---|---|---|---|---|---|
| (I) | 58827 | 4-methoxy-N-(2-phenylacetyl)tryptophan | C20H20N2O4 | 详情 | 详情 | |
| (II) | 58828 | (2R)-3-(4-methoxy-1H-indol-3-yl)-2-[(2-phenylacetyl)amino]propanoic acid | C20H20N2O4 | 详情 | 详情 | |
| (III) | 58829 | (2S)-2-amino-3-(4-methoxy-1H-indol-3-yl)propanoic acid | C12H14N2O3 | 详情 | 详情 | |
| (IV) | 58830 | (2S)-2-{[(benzyloxy)carbonyl]amino}-3-(4-methoxy-1H-indol-3-yl)propanoic acid | C20H20N2O5 | 详情 | 详情 | |
| (V) | 17568 | methyl 2-aminoacetate | C3H7NO2 | 详情 | 详情 | |
| (VI) | 58831 | methyl 2-{[(2S)-2-{[(benzyloxy)carbonyl]amino}-3-(4-methoxy-1H-indol-3-yl)propanoyl]amino}acetate | C23H25N3O6 | 详情 | 详情 | |
| (VII) | 58832 | methyl 2-{[(2S)-2-amino-3-(4-methoxy-1H-indol-3-yl)propanoyl]amino}acetate | C15H19N3O4 | 详情 | 详情 | |
| (VIII) | 18652 | (2S)-2-[[(benzyloxy)carbonyl]amino]-3-(1H-indol-3-yl)propionic acid | 7432-21-5 | C19H18N2O4 | 详情 | 详情 |
| (IX) | 58833 | methyl (5S,8S)-5-(1H-indol-3-ylmethyl)-8-[(4-methoxy-1H-indol-3-yl)methyl]-3,6,9-trioxo-1-phenyl-2-oxa-4,7,10-triazadodecan-12-oate | C34H35N5O7 | 详情 | 详情 | |
| (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 |
合成路线2
该中间体在本合成路线中的序号：(X)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 |