Synthesis of Chiral α‐Trifluoromethyl α,α‐Disubstituted α‐Amino Acids and Conformational Analysis of L‐Leu‐Based Peptides with ( R )‐ or ( S )‐α‐Trifluoromethylalanine
Synthesis of Chiral α‐Trifluoromethyl α,α‐Disubstituted α‐Amino Acids and Conformational Analysis of L‐Leu‐Based Peptides with ( R )‐ or ( S )‐α‐Trifluoromethylalanine
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手性 α-三氟甲基 α,α-二取代 α-氨基酸的合成以及 (R)-或 (S)-α-三氟甲基丙氨酸的 L-Leu 基肽的构象分析
DOI：
10.1002/slct.202002888
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发表时间：
2020
期刊：
影响因子：
2.1
通讯作者：
Tanaka Masakazu
中科院分区：
文献类型：
--
作者：
Ueda Atsushi;Ikeda Misuzu;Kasae Takuya;Doi Mitsunobu;Demizu Yosuke;Oba Makoto;Tanaka Masakazu
通过3，3，3-三氟丙酮酸甲酯亚胺与格氏试剂反应，合成了多种外消旋α-三氟甲基α，α-二取代α-氨基酸。用（R）-1，1 '-联-2-萘酚{（R）-BINOL}酯拆分外消旋体，得到光学活性的α-三氟甲基化α，α-二取代α-氨基酸，如α-三氟甲基丙氨酸（α CF 3Ala）、α-三氟甲基亮氨酸（α CF 3Leu）和α-三氟甲基苯丙氨酸（α CF 3 Phe）。将光学活性的（R）-或（S）-α CF 3Ala掺入到基于L-Leu-的五肽中，并通过傅里叶变换红外（FT-IR）吸收、核奥弗豪瑟效应光谱（NOESY）NMR和圆二色性（CD）光谱以及X射线晶体学分析来研究它们在溶液和晶体状态下的优选构象。具有（R）-或（S）-α CF 3Ala的两种基于L-Leu的肽形成右旋310螺旋结构。N-末端残基1-3处的两个肽骨架非常相似，但具有（R）-或（S）-α CF 3Ala的肽之间的残基4和5的φ和φ扭转角不同。
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 theφandψtorsion angles of residues 4 and 5 between peptides with (R)‐ or (S)‐ αCF3Ala were different.