【结 构 式】 |
【分子编号】48367 【品名】ethyl 2-[(1R)-1-aminoethyl]-1,3-thiazole-4-carboxylate 【CA登记号】 |
【 分 子 式 】C8H12N2O2S 【 分 子 量 】200.26156 【元素组成】C 47.98% H 6.04% N 13.99% O 15.98% S 16.01% |
合成路线1
该中间体在本合成路线中的序号:(XIII)N-Boc-D-alanine (VII) was converted into amide (VIII) via activation as the corresponding mixed anhydride with isobutyl chloroformate. Treatment of amide (VIII) with Lawesson’s reagent gave thioamide (IX). Coupling of (IX) with ethyl bromopyruvate (X) produced the intermediate hydroxythiazoline (XI), which was further dehydrated using trifluoroacetic anhydride to afford the fully protected thiazole amino acid (XII). Removal of the Boc protecting group of (XII) to give (XIII) was achieved by treatment with either trifluoroacetic acid or acetyl chloride in EtOH.
【1】 Xia, Z.; Smith, C.D.; Total synthesis of dendroamide A, a novel cyclic peptide that reverses multiple drug resistance. J Org Chem 2001, 66, 10, 3459. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(VII) | 15859 | Boc-D-Alanine; (2R)-2-[(tert-butoxycarbonyl)amino]propionic acid | 7764-95-6 | C8H15NO4 | 详情 | 详情 |
(VIII) | 46750 | tert-butyl (1R)-2-amino-1-methyl-2-oxoethylcarbamate | C8H16N2O3 | 详情 | 详情 | |
(IX) | 48364 | tert-butyl (1R)-2-amino-1-methyl-2-thioxoethylcarbamate | C8H16N2O2S | 详情 | 详情 | |
(X) | 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 |
(XI) | 48365 | ethyl 2-[(1R)-1-[(tert-butoxycarbonyl)amino]ethyl]-4-hydroxy-4,5-dihydro-1,3-thiazole-4-carboxylate | C13H22N2O5S | 详情 | 详情 | |
(XII) | 48366 | ethyl 2-[(1R)-1-[(tert-butoxycarbonyl)amino]ethyl]-1,3-thiazole-4-carboxylate | C13H20N2O4S | 详情 | 详情 | |
(XIII) | 48367 | ethyl 2-[(1R)-1-aminoethyl]-1,3-thiazole-4-carboxylate | C8H12N2O2S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(XIII)The thiazole amino acid (XIX) was prepared by a similar method as above, consisting of conversion of N-Boc-D-valine (XIV) to the corresponding amide (XV) followed by thionation to (XVI). Condensation of thioamide (XVI) with ethyl bromopyruvate (X) and subsequent acid dehydration gave thiazole (XVIII). Basic hydrolysis of the ethyl ester group of (XVIII) then gave acid (XIX). Coupling of the N-Boc-amino acid (XIX) with aminoester (XIII) produced the corresponding amide (XX). Further acid cleavage of the Boc protecting group gave (XXI).
【1】 Xia, Z.; Smith, C.D.; Total synthesis of dendroamide A, a novel cyclic peptide that reverses multiple drug resistance. J Org Chem 2001, 66, 10, 3459. |
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) | 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 |
(XIII) | 48367 | ethyl 2-[(1R)-1-aminoethyl]-1,3-thiazole-4-carboxylate | C8H12N2O2S | 详情 | 详情 | |
(XIV) | 48375 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-methylbutyric acid | C10H19NO4 | 详情 | 详情 | |
(XV) | 48368 | tert-butyl (1R)-1-(aminocarbonyl)-2-methylpropylcarbamate | C10H20N2O3 | 详情 | 详情 | |
(XVI) | 48369 | tert-butyl (1R)-1-(aminocarbothioyl)-2-methylpropylcarbamate | C10H20N2O2S | 详情 | 详情 | |
(XVII) | 48370 | ethyl 2-[(1R)-1-[(tert-butoxycarbonyl)amino]-2-methylpropyl]-4-hydroxy-4,5-dihydro-1,3-thiazole-4-carboxylate | C15H26N2O5S | 详情 | 详情 | |
(XVIII) | 48371 | ethyl 2-[(1R)-1-[(tert-butoxycarbonyl)amino]-2-methylpropyl]-1,3-thiazole-4-carboxylate | C15H24N2O4S | 详情 | 详情 | |
(XIX) | 48372 | 2-[(1R)-1-[(tert-butoxycarbonyl)amino]-2-methylpropyl]-1,3-thiazole-4-carboxylic acid | C13H20N2O4S | 详情 | 详情 | |
(XX) | 48373 | ethyl 2-((1R)-1-[[(2-[(1R)-1-[(tert-butoxycarbonyl)amino]-2-methylpropyl]-1,3-thiazol-4-yl)carbonyl]amino]ethyl)-1,3-thiazole-4-carboxylate | C21H30N4O5S2 | 详情 | 详情 | |
(XXI) | 48374 | ethyl 2-[(1R)-1-[([2-[(1R)-1-amino-2-methylpropyl]-1,3-thiazol-4-yl]carbonyl)amino]ethyl]-1,3-thiazole-4-carboxylate | C16H22N4O3S2 | 详情 | 详情 |