Asymmetric synthesis of novel highly sterically constrained (2S,3S)-3-methyl-3-trifluoromethyl- and (2S,3S,4R)-3-trifluoromethyl-4-methylpyroglutamic acids

Soloshonok, Vadim A.; Cai, Chaozhong; Hruby, Victor J.; Meervelt, Luc Van

doi:10.1016/s0040-4020(99)00710-3

Cited by 102 publications

(53 citation statements)

References 48 publications

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“…In fact, fluorine editing or fluorine scan is currently a well‐established platform in new drug development allowing for high degree of rational control over physicochemical and biological properties . The second trend is biological application of tailor‐made amino acids (AAs) as structural scaffolds to mimic 3D structure of targeted receptors . The growing acceptance of peptides and modified peptides as drugs, indicates that the role of tailor‐made AAs in the drug design will continue to grow.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Methodsmentioning

confidence: 99%

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

et al. 2020

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“…We have recently demonstrated a one‐step crystal engineering strategy for the formation of several “unnatural”, tailor‐made α ‐amino acid–metal complexes containing racemic mixtures of the chiral ligands, piperazinyl succinic acid, N ‐benzyl aspartic acid, N ‐aminoethyl aspartic acid, and N ‐aminopropyl aspartic acid which are formed under mild hydrothermal conditions in situ by Michael addition of piperazine, benzylamine, ethylenediamine, and 1,3‐diaminopropane to fumaric acid, respectively . This type of Michael reaction, i.e ., the direct amination of α,β‐unsaturated dicarboxylic acid is rarely reported, although the direct amination of α,β‐unsaturated monocarboxylic acid can readily be effected, and several synthetic methods for amination of α,β‐unsaturated dicarboxylic acid derivatives, such as mono‐ or diester and monoamide, are well known …”

Section: Crystallographic Details Formentioning

confidence: 99%

1D Nickel Coordination Polymers with an Unnatural Amino Acid Prepared by in situ Double Michael Addition of Ethylenediamine to (E,E)‐Muconic Acid

Kang

Jung

et al. 2017

Bulletin Korean Chem Soc

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“…The reactions were conducted in a solution of DMF, at ambient temperature, using 15 mol% of organic base DBU. Owing to the high electrophilicity of the trifluoromethyl acrylates 81-83, the reaction rates were exceptionally fast, leading to the completion of the addition within a few minutes [124][125][126]. The observed stereochemical outcome was reasonably good, affording, after disassembly of the corresponding intermediate derivatives, the major diastereomeric products (2S,3S)-84, (2S,3S)-85 and (2S,3S,4R)-86 in isolated yields greater than 50%.…”

Section: Addition Reactionsmentioning

confidence: 99%

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

2009

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Naturally occurring compounds containing a C-F bond are extremely rare; only a handful of fluorine-containing carboxylic acids have been described so far. By contrast, man-made fluorine-containing derivatives of all major classes of biologically important compounds are extremely promising medicinal targets used in the elucidation of biochemical, metabolic transformations and the development of new pharmaceuticals. Among the fluorine-containing derivatives of natural products, fluorinated analogs of amino acids are of particular interest and medicinal potential. This article presents a concise review of various synthetic methods, developed by the Kiev's school of bioorganic chemistry, for the preparation of fluorine-containing analogs of α- and β-amino acids, α-hydroxy acids, amines, as well as their phosphorus and sulfur-derived compounds, in enantiomerically pure form. One of the major methodological goals of the study was practicality, which is understood by us as stereochemical generality, operational convenience and synthetic affordance for each reaction step and isolation of the target products. The synthetic methods developed by our group can be roughly divided in two general categories: fluorine-adaptation of known synthetic approaches and discovery of new reactions. The former approach is most prominently represented by asymmetric homologation of nucleophilic glycine equivalents using fluorinated substrates via alkyl halide alkylations, aldol and Michael addition reactions. A plethora of discovered unexpected reaction outcomes, in particular stereochemical, are emphasized in this review and the particular role of fluorine, in altering the 'normal' reaction result, is explained. The latter direction is notably represented by the novel 1,3-proton shift reaction, a biomimetic reductive amination of fluorinated carbonyl compounds to the corresponding amines and amino acids, as well as the development of α-fluoroalkyl epoxides as true fluorinated synthons for generalized asymmetric synthesis of various biologically relevant compounds. Despite the highly anticipated potential of fluorine-containing amino compounds, their medicinal chemistry still remains underexplored. The major obstacle, in our opinion, is that these selectively fluorinated compounds are generally unavailable to the medicinal chemists for comprehensive, systematic study. We hope this review of synthetic methods will highlight and bring attention to particular types of fluorinated amino acids and related compounds readily available on a laboratory scale using methods developed by our group.

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Asymmetric synthesis of novel highly sterically constrained (2S,3S)-3-methyl-3-trifluoromethyl- and (2S,3S,4R)-3-trifluoromethyl-4-methylpyroglutamic acids

Cited by 102 publications

References 48 publications

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

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

1D Nickel Coordination Polymers with an Unnatural Amino Acid Prepared by in situ Double Michael Addition of Ethylenediamine to (E,E)‐Muconic Acid

Practical Synthesis of Fluorine-Containing α- and β-Amino Acids: Recipes from Kiev, Ukraine

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