Concise synthesis of enantiopure (S)- and (R)-α-trifluoromethyl aspartic acid and α-trifluoromethyl serine from chiral trifluoromethyl oxazolidines (Fox) via a Strecker-type reaction

Recent advances on asymmetric Strecker reactions

“…In 2011, Brigaud and coworkers 32 reported a concise synthesis of enantiopure (S)-and (R)-α-Tfm-aspartic acid (Scheme 4) and α-Tfm-serine (Scheme 5). The key step in the reaction involved a Strecker-type reaction on chiral CF 3 -oxazolidines (Fox) derived from ethyl 4,4,4-trifluoroacetoacetate (ETFAA) or ethyl trifluoropyruvate.…”

Enantiopure α-Trifluoromethylated Aziridine-2-carboxylic Acid (α-TfmAzy): Synthesis and Peptide Coupling

“…The latter can be synthesized in few steps from the (R)-phenylglycinol derived trifluoromethyloxazolidine 3 via a Strecker-type reaction. 19 An alternative pathway consists in performing the cyclization step on the mesylated oxazolidine 4 before or after the introduction of the cyano group through a Strecker-type reaction (Figure 1, path B). Figure 1.…”

“…Strategic pathways for α-TfmAzy synthesis α-trifluoromethyl serines (R)-2 and (S)-2 were synthesized from the ethyl trifluoropyruvate derived oxazolidine 3 through our previously reported procedure (Scheme 2). 19 Since it was anticipated that the protection of the nitrogen atom by a carbamoyl or a tosyl group are not suitable to avoid the Tfmaziridine ring opening in acidic conditions, 29 α-Tfm-serines were protected using a benzyl moiety. The treatment of (R)-2 and (S)-2 with benzyl bromide and potassium carbonate provided the dibenzylated α-Tfm-serines (R)-5 and (S)-5 in 58% and 57% yield respectively (Scheme 1).…”

“…16,17 For several years we have been involved in the development of synthetic methods for the preparation of α-trifluoromethyl amino acids (α-TfmAAs) in enantiomerically pure form. [18][19][20][21][22] Considering the interest of aziridine-2-carboxylate (Azy), as protease inhibitor and the great value of this unnatural amino acid as conformational inducer and late-stage functionalization site, we aimed to develop an efficient and straightforward synthesis of enantiopure α-trifluoromethylated aziridine 2-carboxylic acid (α-TfmAzy) 1. Up today, only few syntheses of αtrifluoromethylated aziridine 2-carboxylic acid derivatives have been reported in the literature (Scheme 1).…”

Synthesis of protected enantiopure (R) and (S)-α-trifluoromethylalanine containing dipeptide building blocks ready to use for solid phase peptide synthesis

“…After separation via chromatography on silica gel and identification of their configuration, these tripeptides were engaged in the SPPS of the antimicrobial peptide. Since several years, we are involved in the synthesis of enantiopure α-Tfm-AAs (Huguenot and Brigaud 2006;Caupene et al 2009;Simon et al 2011;Chaume et al 2009) in order to investigate the physicochemical and biological consequences of their incorporation into peptides. In this context we showed that the incorporation of a α-Tfm-proline at the N-terminal position of a MIF-1 analogue increased its biological activity Bocheva et al 2013).…”