【结 构 式】 |
【分子编号】28898 【品名】(2S)-4-amino-4-oxo-2-[(2-phenylacetyl)amino]butyric acid 【CA登记号】 |
【 分 子 式 】C12H14N2O4 【 分 子 量 】250.25424 【元素组成】C 57.59% H 5.64% N 11.19% O 25.57% |
合成路线1
该中间体在本合成路线中的序号:(VI)Antineopleston A10 (A10) can be obtained by two different ways: 1) A10 has been synthesized in two steps: Condensation of phenylacetic acid (I) with L-glutamine (V) to give phenylacetyl-L-glutamine (VI), followed by intramolecular cyclization of the latter. In the first step (I) is activated by reacting with various reagents such as HOSu (N-hydroxysuccinimide) (II) in the presence of DCC, DCC (N,N-dicyclohexylcarbodiimide) or 2-mercaptothiazoline (III) in the presence of DCC to afford the intermediates (IVa), (IVb) and (IVc), respectively. Without isolation, the intermediate (IVa), (IVb) or (IVc) is treated with a solution of L-glutamine in CH3CN:H2O (2:1) containing NaHCO3 to give (VI) in 60, 87 and 82% yields, respectively. In the second step (VI) is converted to the activated intermediate (IXa) or (IXb) by treatment with CDI (1,1'-carbonydiimidazole) (VII) or HOSu (VIII) in the presence of DCC. Finally, intramolecular cyclization of (IXa) or (IXb) is effected by treating the latter at 80 C to yield A10 in 85 or 82% yield, respectively. 2) Reaction of phenylacetyl chloride with L-glutamine in aqueous solution containing NaHCO3 affords phenylacetyl-L-glutamine (VI), which is heated at 160 C to give A10.
【1】 Verhoef, J.; Schmitz, F.-J.; Fluit, A.C.; Milatovic, D.; 13th Intl Cong Chemother (Aug. 28-Sept. 2, Vienna) 1983, 50, 2, PS 12.4-11-4. |
【2】 Burzynski, S.R. (Burzynski Research Institute); Purified antineoplaston factions and methods of treating neoplastic disease. EP 0069232; JP 5032548; JP 5058886; JP 58010521; US 4470970 . |
【3】 Burzynski, S.R.; Hai, T.T.; Antineoplaston A10. Drugs Fut 1985, 10, 2, 103. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
10101 | Benzyloxycarbonyl chloride; Benzyl chloroformate; 1-[[(Chlorocarbonyl)oxy]methyl]benzene | 501-53-1 | C8H7ClO2 | 详情 | 详情 | |
(IVa) | 24947 | 1-[(2-phenylacetyl)oxy]-2,5-pyrrolidinedione | C12H11NO4 | 详情 | 详情 | |
(IVb) | 28896 | phenylacetic anhydride | C16H14O3 | 详情 | 详情 | |
(IVc) | 28897 | 2-phenyl-1-(2-thioxo-1,3-thiazolidin-3-yl)-1-ethanone | C11H11NOS2 | 详情 | 详情 | |
(IXa) | 28899 | (3S)-4-(1H-imidazol-1-yl)-4-oxo-3-[(2-phenylacetyl)amino]butanamide | C15H16N4O3 | 详情 | 详情 | |
(IXb) | 28900 | (3S)-4-[(2,5-dioxo-1-pyrrolidinyl)oxy]-4-oxo-3-[(2-phenylacetyl)amino]butanamide | C16H17N3O6 | 详情 | 详情 | |
(I) | 16148 | Benzeneacetic acid; 2-Phenylacetic acid; Phenyl Acetic Acid | 103-82-2 | C8H8O2 | 详情 | 详情 |
(II) | 10264 | 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione | 6066-82-6 | C4H5NO3 | 详情 | 详情 |
(III) | 28895 | 4,5-dihydro-1,3-thiazol-2-ylhydrosulfide | 96-53-7 | C3H5NS2 | 详情 | 详情 |
(V) | 24948 | L-glutamine | 56-85-9 | C5H10N2O3 | 详情 | 详情 |
(VI) | 28898 | (2S)-4-amino-4-oxo-2-[(2-phenylacetyl)amino]butyric acid | C12H14N2O4 | 详情 | 详情 | |
(VII) | 11353 | 1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole) | 530-62-1 | C7H6N4O | 详情 | 详情 |
(VIII) | 10264 | 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione | 6066-82-6 | C4H5NO3 | 详情 | 详情 |