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.
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.
Dedicated to Professor Ferenc Fülöp on the occasion of his 70th birthday.Ni(II)-complexes, derived from glycine Schiff bases with chiral tridentate ligands, have been used as powerful tools for the synthesis of structurally diverse tailor-made amino acids. In this manuscript, asymmetric alkylation reaction between chiral nucleophilic glycine derived Ni-complex and 3-(chloromethyl)-1H-pyrrolo[2,3-b]pyridine has been developed under convenient conditions, which affords the corresponding alkylated Nicomplex in 74 % yield and excellent diastereoselectivity (only one isomer). This reaction features convenient conditions and completely controlled diastereoselectivity, which provides a highly valuable approach for asymmetric synthesis of 7-azatryptophan.Amino acids (AAs) belong to the most ubiquitous class of naturally occurring compounds, [1] which have been used as an important type of structural units in the design of modern drugs due to several advantageous features, such as high structural diversity, wide scope of functional groups, good solubility in aqueous media, and few safety concerns. [2] Currently, a number of small-molecule, peptidomimetics, and peptide containing residues of tailor-made AAs or their derivatives serve as key structural features in many blockbuster drugs. [3] Among these natural and non-natural AAs, 7-azatryptophan occupies an important position, which has been widely used as biological fluorescent probes, [4] antiplasmodial compounds, [5] and inhibitors of checkpoint kinase 1. [6,7] Although there have been several reports on the synthesis of aza-tryptophanes, [8] the synthesis of 7-aza-tryptophan still remained less developed, in particular in the asymmetric mode. One of the first asymmetric methods was based on alkylation reaction between (1R,4R)-camphor imine and tert-butylglycinate, which proceeded with poor chemical yield (Scheme 1a). [9] Chemoenzymatic synthesis represents an alternative strategy for the preparation of optical pure 7-aza-tryptophan using aspergillus genus acylase, [10] L-amino acid oxidase [11] or tryptophan synthase from Salmonella typhimurium [12] as biocatalyst[a] Y.
Using platform of a new type of chiral Ni(II) complex of glycine Schiff base we designed addition-cyclization reaction cascade to explore aspects of kinetic/thermodynamic formation of the corresponding (S)(2S,3S)/(S)(2S,3R) diastereomers. It was found that the final lactone products reflect the thermodynamic stereocontrol due to much greater rates of the reversible aldol addition vs. subsequent cyclization step. The observed 4/1 (S)(2S,3S)/(S)(2S,3R) diastereoselectivity in the reactions of new type of (S)-Ni(II) complexes constitute an improvement over the previously reported 1.7/1 ratio.
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