- Robust synthesis of trifluoromethionine and its derivatives by reductive trifluoromethylation of amino acid disulfides by CF3I/Na/Liq.NH 3 system
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We disclose the reductive trifluoromethylation of chemically stable homocystine and cystine to provide corresponding trifluoromethyl ethers by the CF3I/Na/Liq.NH3 system. Both non-protected and protected homocystines can be nicely converted into trifluoromethylated methionines under the same condition. The method described offers a robust synthesis of pharmaceutically important trifluoromethionine, suitable for multigram synthesis. Pentafluoroethylation of homocystine was also achieved by the CF 3CF2I/Na/Liq.NH3 system.
- Yasui, Hiroyuki,Yamamoto, Takeshi,Tokunaga, Etsuko,Shibata, Norio
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- Facile Synthesis of Fluorinated Methionines
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L-Di- and tri-fluoromethylhomocysteines (6) and (7) were efficiently prepared from N-acetylhomocystein thiolactone (3) and the protected monofluoromethylhomocysteine (2) was synthesized from the protected methionine sulphoxide (1).
- Houston, Michael E.,Honek, John F.
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- Simple preparation of trifluoromethionine and derivatives thereof
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Disclosed is a process for the simple preparation of trifluoromethionine, its analogs trifluoromethylcysteine, fluoroalkylhomocysteines, and fluoroalkylcysteines, and derivatives of them. These compounds are drug-candidate compounds or raw materials of drug-candidate compounds. Specifically, trifluoromethionine, trifluoromethylcysteine, a fluoroalkylhomocysteine, or a fluoroalkylcysteine is simply and conveniently prepared directly without passing through homocysteine or cysteine by adding metallic sodium to an optically active or racemic homocystine or cystine in liquid ammonia and further adding a fluoroalkyl iodide thereto under Birch reduction conditions.
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Page/Page column 4
(2011/02/18)
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- Cytotoxic effect of amide derivatives of trifluoromethionine against the enteric protozoan parasite Entamoeba histolytica
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Amoebiasis, caused by infection with the enteric protist Entamoeba histolytica, is one of the major parasitic diseases. Although metronidazole and its derivatives are currently employed in therapy, the paucity of effective drugs and potential clinical resistance necessitate the development of a novel drug. Trifluoromethionine (TFM) is a promising lead compound for antiamoebic drugs. To potentiate the antiamoebic effect of TFM, we synthesised various amide derivatives of TFM and evaluated their cytotoxicity. The amide derivatives of TFM were observed to have a superior cytotoxic effect compared with TFM and metronidazole against E. histolytica in vitro. Although TFM showed cytotoxicity following degradation by methionine γ-lyase, the derivatives were degraded by the enzyme less efficiently compared with TFM. We further demonstrated that a representative derivative was hydrolysed by the amoebic cell lysate to first yield TFM, followed by degradation similar to TFM. Hydrolysis was partially inhibited by protease inhibitors. A single subcutaneous or oral administration of TFM and its amide derivatives also effectively prevented the formation of amoebic liver abscess in a rodent model. These data demonstrate the improved effectiveness of TFM derivatives against E. histolytica infection and elucidate the mechanisms underlining the mode of action of these compounds.
- Sato, Dan,Kobayashi, Seiki,Yasui, Hiroyuki,Shibata, Norio,Toru, Takeshi,Yamamoto, Masaichi,Tokoro, Gensuke,Ali, Vahab,Soga, Tomoyoshi,Takeuchi, Tsutomu,Suematsu, Makoto,Nozaki, Tomoyoshi
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experimental part
p. 56 - 61
(2012/01/04)
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