Various racemic α‐trifluoromethyl α,α‐disubstituted α‐amino acids were synthesized by the reaction of methyl 3,3,3‐trifluoropyruvate imines with Grignard reagents. The optical resolution of racemates using (R)‐1,1’‐bi‐2‐naphthol {(R)‐BINOL} esters gave optically active α‐trifluoromethylated α,α‐disubstituted α‐amino acids, such as α‐trifluoromethylalanine (αCF₃Ala), α‐trifluoromethylleucine (αCF₃Leu), and α‐trifluoromethylphenylalanine (αCF₃Phe). The optically active (R)‐ or (S)‐αCF₃Ala was incorporated into the L–Leu‐based pentapeptides, and their preferred conformation in solution and in the crystal state was studied by Fourier transform infrared (FT‐IR) absorption, nuclear Overhauser effect spectroscopy (NOESY) NMR, and circular dichroism (CD) spectra, as well as X‐ray crystallographic analysis. Both L–Leu‐based peptides with (R)‐ or (S)‐αCF₃Ala formed right‐handed 3₁₀‐helical structures. Both peptide‐backbones at the N‐terminal residues 1–3 were very similar, but the φ and ψ torsion angles of residues 4 and 5 between peptides with (R)‐ or (S)‐ αCF₃Ala were different.

中文翻译：

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手性α-三氟甲基α，α-二取代的α-氨基酸的合成和具有（R）-或（S）-α-三氟甲基丙氨酸的L-Leu基肽的构象分析

通过3,3,3-三氟丙酮酸甲基亚胺与Grignard试剂的反应合成了各种外消旋α-三氟甲基α，α-二取代的α-氨基酸。使用（R）-1,1'-bi-2-萘酚{（R）-BINOL}酯进行消旋体的旋光拆分，得到旋光性α-三氟甲基化的α，α-二取代的α-氨基酸，例如α-三氟甲基丙氨酸（ αCF ₃丙氨酸），α-trifluoromethylleucine（αCF ₃亮氨酸），和α-trifluoromethylphenylalanine（αCF ₃苯丙氨酸）。旋光的（R）‐或（S）‐αCF ₃将Ala掺入基于L–Leu的五肽中，并通过傅里叶变换红外（FT-IR）吸收，核Overhauser效应光谱（NOESY）NMR和圆二色性（CD）研究了它们在溶液和晶体状态下的优选构象）光谱以及X射线晶体学分析。既基于L-LEU-肽（[R ）-或（小号）-αCF ₃丙氨酸形成右旋3层₁₀螺旋结构。两个肽主链在N-末端残基1-3是非常相似的，但是φ和ψ残基4和肽之间5的扭转角（[R ）-或（小号） - αCF ₃丙氨酸是不同的。