(2S,4R)-4-Trifluoromethyl-pseudoproline-benzyl ester

The incorporation of trifluoromethyl group carrying building blocks into peptides results in increased chemical and thermal stability, increased resistance to degradation by proteases, and enhanced lipophilicity, i.e. better affinity to lipid membranes. Stabilization of particular conformations and auto-assembly can be induced. Also useful as label for 19F-NMR studies. ?-Trifluoromethyl substituted amino acids are, therefore, very attractive building blocks for the design of biologically active compounds. References: V. P. Kukhar, V. A. Soloshonok in Fluorine Containing Amino Acids: Synthesis and Properties, Wiley, New York, 1995. B. Koksch, N. Sewald, H.-J. Hofmann, K. Burger, H.-D. Jakubke, J. Pept. Sci. 1997; 3: 157-167. 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. f) F. Lazzaro, M. Crucianelli, F. De Angelis, M. Frigerio, L. Malpezzi, A. Volonteriob, M. Zanda, Tetrahedron: Asymmetry 2004; 15: 889-893. P. K. Mykhailiuk, S. Afonin, G. V. Palamarchuk, O. V. Shishkin, A. S. Ulrich, I. Komarov, Angew. Chem. Int. Ed. 2008; 47: 5765-5767. 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. 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. Convenient Synthesis of N-Terminal Tfm-Dipeptides from Unprotected Enantiopure ?-Tfm-Proline and ?-Tfm-Alanine; Grégory Chaume, Nathalie Lensen, Caroline Caupène, and Thierry Brigaud; Eur. J. Org. Chem. 2009; 5717-5724. Concise access to enantiopure (S)- and (R)-?-trifluoromethyl pyroglutamic acids from ethyl trifluoropyruvate-based chiral CF3-oxazolidines (Fox); Grégory Chaume, Marie-Céline Van Severen, Louis Ricard, Thierry Brigaud; J. Fluorine Chem. 2008; 129: 1104-1109. 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. Straightforward Synthesis of (S)- and (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. Iodocyclization of Chiral CF3-Allylmorpholinones: A Versatile Strategy for the Synthesis of Enantiopure ?-Tfm-Prolines and ?-Tfm-Dihydroxyprolines; Caroline Caupène, Grégory Chaume, Louis Ricard, and Thierry Brigaud; Org. Lett. 2009; 11 (1): 209-212. Julien Simon, Thi Thuan Nguyen, Evelyne Chelain, Nathalie Lensen, Julien Pytkowicz, Grégory Chaume, Thierry Brigaud in press Tetrahedron: Asymmetry 2011. doi:10.1016/j.tetasy.2011.01.007.