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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Concise Access to (S)- and (R)-α-Tfm Serine and α-TfmAspartic Acid From Chiral Trifluoromethyloxazolidines (Fox)Julien Simon, Thuan Nguyen, Grégory Chaume, Evelyne Chelain,Nathalie Lensen, Julien Pytkowicz, and Thierry BrigaudLaboratoire SOSCO, Université de Cergy-Pontoise, 5, mail Gay Lussac,Cergy-Pontoise, F-95000, FranceIntroductionα-Trifluoromethylated amino acids (α-Tfm AAs) are current synthetic targets due to theunique physical and biological properties imparted by the fluorinated group. However, theirpreparation in enantiopure form remains a challenge [1-3]. Our group is involved in thedevelopment of efficient synthetic routes for the preparation of enantiopure α-Tfm AAsstarting from chiral CF 3 -oxazolidines (Fox) or imines [4-9] and their incorporation into apeptide chain [10]. We will report here the straightforward preparation of both enantiomersof α-Tfm-serine and α-Tfm-aspartic acid in enantiopure form starting from oxazolidinesderived respectively from ethyl trifluoropyruvate and ethyl 4,4,4-trifluoroacetoacetate(ETFAA). The key step of both synthesis involves a Strecker-type reaction.Results and DiscussionThe synthesis of both enantiomers of α-Tfm-serine started with the preparation of the chiralCF 3 -oxazolidine derived from ethyl trifluoropyruvate and (R)-phenylglycinol (Figure 1).We already reported that when using LiAlH 4 as reducing reagent, the ester reduction of theoxazolidine was accompanied with its ring opening [11]. Nevertheless, we hypothesizedthat the use of a less reactive reducing reagent should allow the chemoselective reductionof the ester group thank to the high degree of activation of the ester moiety by the CF 3group. Thus, using NaBH 4 , the ester group of the oxazolidine was selectively reduced. AFig. 1. Synthesis of (S)- and (R)-α-Tfm-Serine in enantiopure form.Strecker-type reaction was then successfully performed to afford the corresponding aminonitriles. After separation of the respective major (S,R) and minor (R,R) diastereomer bysilica gel chromatography, the clean removal of the chiral auxiliary and hydrolysis of thenitrile group occurred in a one step procedure using concentrated HCl to afford respectivelythe (R)- and the (S)-α-Tfm-serine in enantiopure form and in good overall yield. Absoluteconfiguration was attributed thanks to correlation with the optical rotation reported in theliterature [12].The straightforward access of both enantiomers of α-Tfm-aspartic acid involved thepreparation of the ethyl 4,4,4-trifluoroacetoacetate-based CF 3 -oxazolidine. Following aFig. 2. Strecker-type reaction from ethyl 4,4,4-trifluoroacetoacetate-based CF 3 -oxazolidine.74