1. 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.
2. Asymmetric synthesis of (S)-α-(octyl)glycine via alkylation of Ni(II) complex of chiral glycine Schiff base
Bo Fu, Ryosuke Takeda, Yupiao Zou, Hiroyuki Konno, Hiroki Moriwaki, Hidenori Abe, Jianlin Han, Kunisuke Izawa, Vadim A Soloshonok Chirality. 2020 Dec;32(12):1354-1360. doi: 10.1002/chir.23281.
Over last decade, the use of Ni(II) complexes, derived from of glycine Schiff bases with chiral tridentate ligands, has emerge as a leading methodology for preparation of structurally diverse Tailor-Made Amino Acids, the key structural units in modern medicinal chemistry, and drug design. Here, we report asymmetric synthesis of derivatives of (S)-α-(octyl)glycine ((S)-2-aminodecanoic acid) and its N-Fmoc derivative via alkylation of chiral nucleophilic glycine equivalent with n-octyl bromide. Under the optimized conditions, the alkylation proceeds with excellent yield (98.1%) and diastereoselectivity (98.8% de). The observed stereochemical outcome and convenient reaction conditions bode well for application of this method for large-scale asymmetric synthesis of (S)-2-aminodecanoic acid and its derivatives.
3. Asymmetric Synthesis of 4,4-(Difluoro)glutamic Acid via Chiral Ni(II)-Complexes of Dehydroalanine Schiff Bases. Effect of the Chiral Ligands Structure on the Stereochemical Outcome
Yoshinori Tokairin, Yuhei Shigeno, Jianlin Han, Gerd-Volker Röschenthaler, Hiroyuki Konno, Hiroki Moriwaki, Vadim A Soloshonok ChemistryOpen. 2020 Jan 29;9(1):93-96. doi: 10.1002/open.201900343. eCollection 2020 Jan.
Four differently substituted chiral Ni(II)-complexes of dehydroalanine Schiff base were prepared and reacted with BrCF2COOEt/Cu under the standard reaction conditions. The observed diastereoselectivity was found to depend on the degree and pattern of chlorine substitution for hydrogen in the structure of the dehydroalanine complexes. The unsubstituted complex gave the ratio of diastereomers (S)(2S)/(S)(2R) of 66/34. On the other hand, introduction of chlorine atoms in the strategic positions on the chiral ligands allowed to achieve a practically attractive diastereoselectivity of (~98.5/1.5). Diastereomerically pure major product was disassembled to prepare 9-fluorenylmethyloxycarbonyl (Fmoc) derivative of (S)-4,4-difluoroglutamic acid.
