1. Advanced asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid by alkylation/cyclization of newly designed axially chiral Ni(II) complex of glycine Schiff base
Aki Kawashima, et al. Amino Acids. 2016 Apr;48(4):973-986. doi: 10.1007/s00726-015-2138-3. Epub 2015 Dec 11.
Asymmetric synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is in extremely high demand due to the pharmaceutical importance of this tailor-made, sterically constrained α-amino acid. Here we report the development of an advanced procedure for preparation of the target amino acid via two-step SN2 and SN2' alkylation of novel axially chiral nucleophilic glycine equivalent. Excellent yields and diastereoselectivity coupled with reliable and easy scalability render this method of immediate use for practical synthesis of (1R,2S)-vinyl-ACCA.
2. Asymmetric Synthesis of Tailor-Made Amino Acids Using Chiral Ni(II) Complexes of Schiff Bases. An Update of the Recent Literature
Yupiao Zou, Jianlin Han, Ashot S Saghyan, Anna F Mkrtchyan, Hiroyuki Konno, Hiroki Moriwaki, Kunisuke Izawa, Vadim A Soloshonok Molecules. 2020 Jun 12;25(12):2739. doi: 10.3390/molecules25122739.
Tailor-made amino acids are indispensable structural components of modern medicinal chemistry and drug design. Consequently, stereo-controlled preparation of amino acids is the area of high research activity. Over last decade, application of Ni(II) complexes of Schiff bases derived from glycine and chiral tridentate ligands has emerged as a leading methodology for the synthesis of various structural types of amino acids. This review article summarizes examples of asymmetric synthesis of tailor-made α-amino acids via the corresponding Ni(II) complexes, reported in the literature over the last four years. A general overview of this methodology is provided, with the emphasis given to practicality, scalability, cost-structure and recyclability of the chiral tridentate ligands.
3. Asymmetric synthesis of (S)-3-methyleneglutamic acid and its N-Fmoc derivative via Michael addition-elimination reaction of chiral glycine Ni (II) complex with enol tosylates
Yuhei Shigeno, Jianlin Han, Vadim A Soloshonok, Hiroki Moriwaki, Wataru Fujiwara, Hiroyuki Konno 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™.
