(R)-Trifluoromethylalanine

a-Trifluoromethyl substituted amino acids are very attractive compounds for the design of biologically active compounds [1]. The incorporation of trifluoromethyl groups carrying building blocks into peptides can result in increase chemical and thermal stability, increased resistance to degradation by proteases [2], and enhanced lipophilicity, i.e. better affinity to lipid membranes. Stabilization of particular conformations and auto-assembly [3] can be induced. Also useful as label for 19F-NMR studies [4]. References: [1] V. P. Kukhar, V. A. Soloshonok in Fluorine Containing Amino Acids: Synthesis and Properties, Wiley, New York, 1995. [2] B. Koksch, N. Sewald, H.-J. Hofmann, K. Burger, H.-D. Jakubke, J. Pept. Sci. 1997; 3: 157-167. [3] a) C. Jaeckel, B. Koksch, Eur. J. Org. Chem. 2005; 4483-4503; b) N. C. Yoder, K. Kumar, Chem. Soc. Rev. 2002; 31: 335-341; c) H. Meng, K. Kumar, J. Am. Chem. Soc. 2007; 129: 15615-15622; d) M. Molteni, C. Pesenti, M. Sani, A. Volonterio, M.Zanda, J. Fluorine Chem. 2004; 125: 1335-1743; e) M. Zanda, New J. Chem. 2004; 28: 1401-1411. [4] a) P. K. Mykhailiuk, S. Afonin, G. V. Palamarchuk, O. V. Shishkin, A. S. Ulrich, I. Komarov, Angew. Chem. Int. Ed. 2008; 47: 5765-5767; b) S. L. Grage, U. H. N. Duerr, S. Afonin, P. K. Mikhailiuk, I. V. Komarov, A. S. Ulrich, J. Magn. Reson. 2008; 191: 16-23; c) P. K. Mikhailiuk, S. Afonin, A. N. Chernega, E. B. Rusanov, M. O. Platonov, G. G. Dubinina, M. Berditsch, A. S. Ulrich, I. V. Komarov, Angew. Chem. Int. Ed. 2006; 45: 5659-5661. Additional References: [5] Convenient Synthesis of N-Terminal Tfm-Dipeptides from Unprotected Enantiopure a-Tfm-Proline and a-Tfm-Alanine; Grégory Chaume, Nathalie Lensen, Caroline Caupène, and Thierry Brigaud; Eur. J. Org. Chem. 2009; 5717-5724. [6] Concise access to enantiopure (S)- and (R)-a-trifluoromethyl pyroglutamic acids from ethyl trifluoropyruvate-based chiral CF3-oxazolidines (Fox); Grégory Chaume, Marie-Céline Van Severen, Louis Ricard, Thierry Brigaud; Journal of Fluorine Chemistry 2008; 129: 1104-1109. [7] Synthesis of 2-Trifluoromethyl-1,3-oxazolidines as Hydrolytically Stable Pseudoprolines; Grégory Chaume, Olivier Barbeau, Philippe Lesot, and Thierry Brigaud; J. Org. Chem. 2010; 75: 4135-4145. [8] Straightforward Synthesis of (S)- and (R)-r-Trifluoromethyl Proline from Chiral Oxazolidines Derived from Ethyl Trifluoropyruvate; Grégory Chaume, Marie-Céline Van Severen, Sinisa Marinkovic, and Thierry Brigaud; Org. Lett., 2006; 8(26): 6123-6126. [9] Iodocyclization of Chiral CF3-Allylmorpholinones: A Versatile Strategy for the Synthesis of Enantiopure a-Tfm-Prolines and a-Tfm-Dihydroxyprolines; Caroline Caupène, Grégory Chaume, Louis Ricard, and Thierry Brigaud; Org. Lett. 2009; 11 (1): 209-212.