【结 构 式】 |
【分子编号】26279 【品名】(2S)-2-amino-3-(1-methoxy-1H-indol-3-yl)propionic acid 【CA登记号】 |
【 分 子 式 】C12H14N2O3 【 分 子 量 】234.25484 【元素组成】C 61.53% H 6.02% N 11.96% O 20.49% |
合成路线1
该中间体在本合成路线中的序号:(XVIII)Condensation of phenylacetic acid (XI) with methoxyamine gave hydroxamate (XII). After N-chlorination of (XII) with tert-butyl hypochlorite, Ag(I)-catalyzed ring closure of the intermediate (XIII) produced N-(methoxy)oxindole (XIV). Amide reduction of (XIV) with LiAlH4 gave hemiaminal (XV), which was converted to the racemic tryptophan derivative (XVII) by reaction with alpha-acetamidoacrylic acid (XVI) in AcOH-Ac2O. Optical resolution of (XVII) by enantioselective enzymatic hydrolysis of the acetamide group using Acylase I from Aspergillus sp. afforded N1'-methoxy-L-tryptophan (XVIII), which was protected as the N-Boc derivative (XIX) and N-methylated by means of MeI and NaH yielding (XX). The resulting N-methyl amino acid (XX) was esterified upon treatment with (trimethylsilyl)diazomethane giving (XXI), and the N-Boc group was removed with HCl in EtOAc to provide the tryptophan derivative (XXII).
【1】 Boger, D.L.; et al.; Total synthesis of HUN-7293. J Am Chem Soc 1999, 121, 26, 6197. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
15455 | (aminooxy)methane; O-methylhydroxylamine | 67-62-9 | CH5NO | 详情 | 详情 | |
(XI) | 16148 | Benzeneacetic acid; 2-Phenylacetic acid; Phenyl Acetic Acid | 103-82-2 | C8H8O2 | 详情 | 详情 |
(XII) | 26273 | N-methoxy-2-phenylacetamide | C9H11NO2 | 详情 | 详情 | |
(XIII) | 26274 | N-chloro-N-methoxy-2-phenylacetamide | C9H10ClNO2 | 详情 | 详情 | |
(XIV) | 26275 | 1-methoxy-1,3-dihydro-2H-indol-2-one | C9H9NO2 | 详情 | 详情 | |
(XV) | 26276 | 1-methoxy-2-indolinol | C9H11NO2 | 详情 | 详情 | |
(XVI) | 26277 | 2-(acetamido)acrylic acid | 5429-56-1 | C5H7NO3 | 详情 | 详情 |
(XVII) | 26278 | N-acetyl-1-methoxytryptophan | C14H16N2O4 | 详情 | 详情 | |
(XVIII) | 26279 | (2S)-2-amino-3-(1-methoxy-1H-indol-3-yl)propionic acid | C12H14N2O3 | 详情 | 详情 | |
(XIX) | 26280 | (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1-methoxy-1H-indol-3-yl)propionic acid | C17H22N2O5 | 详情 | 详情 | |
(XX) | 26281 | (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-(1-methoxy-1H-indol-3-yl)propionic acid | C18H24N2O5 | 详情 | 详情 | |
(XXI) | 26282 | methyl (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-(1-methoxy-1H-indol-3-yl)propanoate | C19H26N2O5 | 详情 | 详情 | |
(XXII) | 26283 | methyl (2S)-3-(1-methoxy-1H-indol-3-yl)-2-(methylamino)propanoate | C14H18N2O3 | 详情 | 详情 |