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【结 构 式】 
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【分子编号】29436 【品名】(2S)-2-amino-5-[[(1R)-2-[(carboxymethyl)amino]-2-oxo-1-(sulfanylmethyl)ethyl]amino]-5-oxopentanoic acid 【CA登记号】70-18-8 |
【 分 子 式 】C10H17N3O6S 【 分 子 量 】307.3276 【元素组成】C 39.08% H 5.58% N 13.67% O 31.24% S 10.43% |
合成路线1
该中间体在本合成路线中的序号：(IV)Treatment of 4-chlorophenyl chloroformate (I) with N-(4-chlorophenyl) hydroxylamine (II) produced the N-hydroxycarbamate (III). This was condensed with glutathione (IV) to afford thiocarbamate (V). Finally, both carboxylate groups of (V) were esterified in ethanolic HCl to provide the target diethyl ester.
| 【1】 Sentz, D.L.; Kavarana, M.J.; O'Neill, H.B.; Wang, H.; Eiseman, J.L.; Sharkey, E.M.; Creighton, D.J.; Pharmacokinetics and antitumor properties in tumor-bearing mice of an enediol analogue inhibitor of glyoxalase I. Cancer Chemotherapy and Pharmacology 2000, 46, 2, 156. |
| 【2】 Kavarana, M.J.; Kovaleva, E.G.; Creighton, D.J.; Wollman, M.B.; Eiseman, J.L.; Mechanism-based competitive inhibitors of glyoxalase I: Intracellular delivery, in vitro antitumor activities, and stabilities in human serum and mouse serum. J Med Chem 1999, 42, 2, 221. |
| 【3】 Muthy, N.S.R.K.; et al.; S-(N-Aryl-N-hydroxycarbamoyl)glutathione derivatives are tight-binding inhibitors of Glyoxalase I and Slow Substrates for Glyoxalase II. J Med Chem 1994, 37, 14, 2161-2166. |
| 【4】 Creighton, D.J.; Hamilton, D.S. (University of Maryland); Glutathione N-hydroxycarbamoyl thioesters and method of inhibiting neoplastic growth. US 5616563; WO 9600061 . |
| 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) | 17779 | 1-chloro-4-[(chlorocarbonyl)oxy]benzene | 7693-45-0 | C7H4Cl2O2 | 详情 | 详情 |
| (II) | 29435 | 1-chloro-4-(hydroxyamino)benzeneN-(4-chlorophenyl)hydroxylamine | C6H6ClNO | 详情 | 详情 | |
| (III) | 29438 | 4-chlorophenyl 4-chlorophenyl(hydroxy)carbamate | C13H9Cl2NO3 | 详情 | 详情 | |
| (IV) | 29436 | (2S)-2-amino-5-[[(1R)-2-[(carboxymethyl)amino]-2-oxo-1-(sulfanylmethyl)ethyl]amino]-5-oxopentanoic acid | 70-18-8 | C10H17N3O6S | 详情 | 详情 |
| (V) | 29437 | (2S)-2-amino-5-([(1R)-2-[(carboxymethyl)amino]-1-[([[4-chloro(hydroxy)anilino]carbonyl]sulfanyl)methyl]-2-oxoethyl]amino)-5-oxopentanoic acid | C17H21ClN4O8S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(I)Darinaparsin can be obtained by reaction of glutathione (I) under nitrogen atmosphere with either dimethylchloroarsine (II) in the presence of pyridine in dimethoxyethane (1, 2) or water/ethanol (3), or with dimethylarsinic acid (III) in water (4). Scheme 1.
| 【1】 Zingaro, R.A., Freireich, E.L., Sotelo-Lerma, M., Kantarjian, H., Verstovsek, S., Dukale, H. (University of Texas System; Texas A&M University). S-Dimethylarsino-thiosuccinic acid S-dimethylarsino-2-thiobenzoic acid S-(dimethylarsino)glutathione as treatments for cancer. CA 2472633, EP 1474128, JP 2005527487, US 2004034095, US 6911471, WO 2003057012. |
| 【2】 Zingaro, R.A., Duzkale, H., Freireich, E.J., Kantarjian, H., Sotelo-Lerma, M., Verstovsek, S., Gao, M. (Texas A&M University; University of Texas System). Compounds and methods for treatment of cancer. EP 1771459, JP 2008506710, WO 2006020048. |
| 【3】 Gutsch, P., Renzelmann, B. (Ziopharm Oncology, Inc.). Compounds and methods for the treatment of cancer. CA 2617049, EP 1919564, JP 2009502971, US 2007183972, WO 2007027344. |
| 【4】 Cullen, W.R., McBride, B.C., Reglinski, J. The reaction of methylarsenicals with thiols: Some biological implications. J Inorg Biochem 1984, 21(3): 179-94. |
| 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) | 29436 | (2S)-2-amino-5-[[(1R)-2-[(carboxymethyl)amino]-2-oxo-1-(sulfanylmethyl)ethyl]amino]-5-oxopentanoic acid | 70-18-8 | C10H17N3O6S | 详情 | 详情 |
| (II) | 65826 | Chlorodimethylarsine; Chloro-Dimethyl-Arsane | 557-89-1 | C2H6AsCl | 详情 | 详情 |
| (III) | 65827 | Cacodylic acid; Dimethylarsinic acid | 75-60-5 | C2H7AsO2 | 详情 | 详情 |