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Review
. 2020 Jun 12;25(12):2739.
doi: 10.3390/molecules25122739.

Asymmetric Synthesis of Tailor-Made Amino Acids Using Chiral Ni(II) Complexes of Schiff Bases. An Update of the Recent Literature

Yupiao Zou  1 , Jianlin Han  1 , Ashot S Saghyan  2   3 , Anna F Mkrtchyan  2   3 , Hiroyuki Konno  4 , Hiroki Moriwaki  5 , Kunisuke Izawa  5 , Vadim A Soloshonok  6   7
Affiliations
Review

Asymmetric Synthesis of Tailor-Made Amino Acids Using Chiral Ni(II) Complexes of Schiff Bases. An Update of the Recent Literature

Yupiao Zou et al. Molecules. .

Abstract

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.

Keywords: Schiff bases; asymmetric synthesis; chiral tridentate ligands; square-planar Ni(II) complexes; tailor-made amino acids.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Asymmetric synthesis of tailor-made amino acid via Ni(II) complexes of Schiff bases.
Figure 1
Figure 1
Chiral tridentate ligands.
Scheme 2
Scheme 2
Large-scale synthesis of ligand 16 and complex 18.
Scheme 3
Scheme 3
Synthesis of Ni(II) complex 18 from 16.
Figure 2
Figure 2
Structure of Hamari ligand.
Scheme 4
Scheme 4
Methods for the synthesis of Hamari ligand 19 ((a) synthetic method from chiral binaphthol; (b) synthetic method via a one-step substitution alkylation reaction).
Scheme 5
Scheme 5
Preparation of glycinamide hydrochloride 24.
Scheme 6
Scheme 6
Dynamic kinetic/thermodynamic resolution of phenylalanine with concurrent deuteration using ligand (S)-16.
Scheme 7
Scheme 7
Preparation of complex (S)(S)-27.
Scheme 8
Scheme 8
Synthesis of (S)-2-amino-4,4,4-trifluorobutanoic acid.
Scheme 9
Scheme 9
Synthesis of N-Fmoc-(S)-6,6,6-trifluoronorleucine.
Scheme 10
Scheme 10
Synthesis of (R)(S)- and (R)(R)-35 via Hamari ligand.
Scheme 11
Scheme 11
Synthesis of (R)(S)- and (R)(R)-37 via Soloshonok ligand.
Scheme 12
Scheme 12
Synthesis of prepared the chiral amino acid (R)-39.
Scheme 13
Scheme 13
Synthesis of chiral α-substituted amino acids.
Scheme 14
Scheme 14
Synthesis of α,α-disubstituted amino acid.
Scheme 15
Scheme 15
Synthesis of chiral ligand 50 containing rimantadine group.
Scheme 16
Scheme 16
SOAT approach for the preparation of Ni complexes.
Scheme 17
Scheme 17
Disassembly of 51a.
Scheme 18
Scheme 18
Synthesis of Ni complexes with glycine derivatives by SOAT.
Scheme 19
Scheme 19
The disassembly procedure of 51a.
Scheme 20
Scheme 20
Synthesis of α,α-disubstituted amino acid derivative.
Scheme 21
Scheme 21
An improved synthesis route to α,α-disubstituted amino acid derivatives.
Scheme 22
Scheme 22
Synthesis of Fmoc amino acid 61.
Figure 3
Figure 3
Structure of three spin-labeled target amino acids (62–64).
Scheme 23
Scheme 23
Synthesis of the spin-labeled amino acid 62.
Scheme 24
Scheme 24
Synthesis of chiral spin-labeled amino acids 63 and 64.
Scheme 25
Scheme 25
Asymmetric 1,6-conjugate addition reaction of Ni(II) complex 2.
Scheme 26
Scheme 26
Asymmetric Michael addition of Ni(II) complex 2 with β-trifluoromethylated-α,β-unsaturated ketones.
Scheme 27
Scheme 27
Reduction of (2S,3S)-74a.
Scheme 28
Scheme 28
Synthesis of complexes 77a and 77b.
Scheme 29
Scheme 29
Asymmetric aza-Michael addition of indoles.
Scheme 30
Scheme 30
Michael-type addition reaction between achiral complex of dehydroalanine and ethyl bromodifluoroacetate.
Scheme 31
Scheme 31
Asymmetric synthesis of difluoroglutamic acid derivative (S)-86 via Michael-type addition reaction between chiral complex (S)-84 and ethyl bromodifluoroacetate.
Scheme 32
Scheme 32
Asymmetric synthesis of optical active 3-Me-glutamine derivatives 89 and 90 via Michael-type addition reaction between chiral complex (S)-18 and crotonate.
Scheme 33
Scheme 33
Suzuki reaction between (S)-91 and different boric acids.
Scheme 34
Scheme 34
Fe-catalyzed coupling reaction of Ni complex 78.
Scheme 35
Scheme 35
Electrochemical stereoselective oxyalkylation of the (S)-2.
Scheme 36
Scheme 36
Alkylation of chiral glycine equivalent (S)-18.
Scheme 37
Scheme 37
DKR of 2-amino-5,5,5-trifluoropentanoic acid (100).
Scheme 38
Scheme 38
Reaction of 101 with phenylalanine.
Scheme 39
Scheme 39
Synthetic approach to ligands (S)- and (R)-106–109.
Scheme 40
Scheme 40
Chemical resolution of β-phenyl-β-alanine 110 with new chiral ligands 106–109.
Scheme 41
Scheme 41
Asymmetric synthesis of chiral α-benzyl mercaptoglycine derivatives.
Scheme 42
Scheme 42
Electrochemical reaction of Ni complex and thiocyanates.
Scheme 43
Scheme 43
Synthesis of triazoles via click reaction of Ni complex (S)-115.
Scheme 44
Scheme 44
Disassembly of the Ni complex (S)-116 to give free amino acid (S)-117.
Scheme 45
Scheme 45
Synthesis of Ni(II) complex (S)-119 and its click reaction.
Scheme 46
Scheme 46
Structure of Ni complex 121a-h and their methylation derivatives.
Scheme 47
Scheme 47
Synthesis of ligand 123 and racemic glycine Schiff base Ni(II) complex 124.
Scheme 48
Scheme 48
Structures of complex 125–134.
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