Department of Biological Engineering, Graduate School of Science and Engineering, Yamagata University, Yamagata, Japan.
Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, College of Chemical Engineering, Nanjing Forestry University, Nanjing, China.
Chirality. 2021 Mar;33(3):115-123. doi: 10.1002/chir.23291. Epub 2020 Dec 26.
The use of chiral Ni (II)-complexes of glycine Schiff bases has recently emerged as a leading methodology for asymmetric synthesis of structurally diverse Tailor-Made Amino Acids™, playing a key role in the design of modern pharmaceuticals. Here, we report first example of enantioselective preparation of (S)-3-methyleneglutamic acid and its N-Fmoc derivative via a new type of Michael addition-elimination reaction between chiral nucleophilic glycine equivalent and enol tosylates. This reaction was found to proceed with excellent yield (91%) and diastereoselectivity (>99/1 de) allowing straightforward asymmetric synthesis of (S)-3-methyleneglutamic acid derivatives and analogues. The observed results bode well for general application of this Ni (II) complex approach for preparation and biological studies of this previously unknown type of Tailor-Made Amino Acids™.
手性 Ni(II)-甘氨酸席夫碱配合物在不对称合成结构多样的定制氨基酸™方面的应用最近成为一种主流方法，在手性药物设计中发挥着关键作用。在此，我们报告了首例通过手性亲核甘氨酸等价物与烯醇对甲苯磺酸盐之间的新型迈克尔加成-消除反应，对 (S)-3-亚甲基谷氨酸及其 N-Fmoc 衍生物进行对映选择性制备的例子。该反应以优异的收率（91%）和非对映选择性（>99/1 de）进行，允许通过直接不对称合成（S）-3-亚甲基谷氨酸衍生物和类似物。观察到的结果为该 Ni(II)配合物方法在这种以前未知类型的定制氨基酸™的制备和生物学研究中的广泛应用提供了良好的前景。
