【结 构 式】 |
【药物名称】Antineoplaston AS2-5 【化学名称】N2-Phenylacetyl-L-glutamine sodium salt 【CA登记号】104771-87-1, 28047-15-6 (free acid), 31427-44-8 (free acid) 【 分 子 式 】C13H15N2NaO4 【 分 子 量 】286.2653 |
【开发单位】Burzynski Research Institute (Originator), National Cancer Institute (Not Determined) 【药理作用】Oncolytic Drugs, Prostate Cancer Therapy |
合成路线1
Antineoplaston AS2-5 (AS2-5) can be obtained in the following way (1,2): N-Phenylacetyl-L-glutamine sodium is synthesized in two steps. In the first step, phenylacetic acid (I) is treated with N-hydroxysuccinimide (B) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (A) in acetonitrile to give intermediate (Ia). In the second step, (Ia) is reacted without purification with L-glutamine (II) in the presence of NaHCO3 in 1:1 acetonitrile-water mixture to afford N-phenylacetyl-L-glutamine (III) in 87% yield. Compound (III) is then converted to sodium salt in aqueous solution by treatment with aqueous sodium hydroxide solution (pH 7). In a large scale preparation reaction of phenylacetyl chloride with L-glutamine in aqueous solution containing NaHCO3 affords N-phenyiacetyl L-glutamine sodium.
【1】 Burzynski, S.R. (Burzynski Research Institute); Purified antineoplaston fractions and methods of treating neoplastic disease. US 4558057 . |
【2】 Berman, E.M.; Gregor, V.E.; Showalter, H.H.D. (Pfizer Inc.); Benzoselenino[4,3,2-cd]indazole compound, compositions comprising the compounds and processes for producing the compounds. AU 8544154; EP 0170412; ES 8704956 . |
【3】 Khalid, M.; Burzynski, S.R.; Antineoplaston AS2-5. Drugs Fut 1986, 11, 5, 364. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(B) | 10264 | 1-Hydroxydihydro-1H-pyrrole-2,5-dione; N-Hydroxysuccinimide; 1-Hydroxy-2,5-pyrrolidinedione | 6066-82-6 | C4H5NO3 | 详情 | 详情 |
(Ia) | 24927 | tert-butyl (2R,3aR,7aR,10aR)-8-(dimethoxymethyl)-5-(5-hexenyl)-10-oxo-2-vinyl-2,3,5,6,7,7a,10,10a-octahydropyrrolo[2,3-i]isoquinoline-1(4H)-carboxylate | C27H42N2O5 | 详情 | 详情 | |
(A) | 24945 | N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide | 25952-53-8 | C8H17N3 | 详情 | 详情 |
(I) | 16148 | Benzeneacetic acid; 2-Phenylacetic acid; Phenyl Acetic Acid | 103-82-2 | C8H8O2 | 详情 | 详情 |
(II) | 24948 | L-glutamine | 56-85-9 | C5H10N2O3 | 详情 | 详情 |
(III) | 24949 | (2S)-5-amino-5-oxo-2-[(2-phenylacetyl)amino]pentanoic acid | C13H16N2O4 | 详情 | 详情 |