Asymmetric Synthesis Of Amino Acids Research Articles

Asymmetric Metal‐Templated Approach to Amino Acids with a CF3‐Containing 3,2’‐Pyrrolidinyl Spirooxindole Core via a Michael/Mannich [3+2]‐Cycloaddition Reaction

AbstractWe report here a practical protocol for the asymmetric synthesis of amino acids (AAs) with a CF3‐containing 3,2’‐pyrrolidinyl spirooxindole skeleton with three defined carbon stereocenters via a sequential Michael/Mannich [3+2]‐cycloaddition reaction. The coupling of a robust and stereochemically stable chiral dehydroalanine Ni(II) complex with various N‐2,2,2‐trifluoroethylisatin ketimines in the presence of triethylamine afforded a library of single diastereomeric complexes with a 3,2’‐pyrrolidinyl spirooxindole moiety in 36–71% yields. In particular, the change of base to LiOH allowed to obtain predominantly the Michael addition product in 76% yield. Finally, the decomposition of the obtained Ni(II) complexes with 3 N HCl provided the target complex AA with a 3,2’‐pyrrolidinyl spirooxindole core and (2S,4R)‐2,4‐diamino‐5,5,5‐trifluoropentanoic acid – an (S)‐norvaline derivative, together with easy recovery of the chiral auxiliary ligand for the synthesis of the starting dehydroalanine complex.

Advances in Asymmetric Amino Acid Synthesis Enabled by Radical Chemistry

AbstractChiral amino acids (AAs), being the main “building” blocks of the living organisms, are also an important class of organic compounds which broadly applied in synthetic chemistry, biochemistry, catalysis and the designing of new drugs. According to the industrial‐commodity market, chiral non‐proteinogenic AAs containing various functional groups come to the fore. To date, radical cross‐coupling reactions are becoming an option as an attractive powerful tool for AA syntheses. Owing to mild reaction conditions and high functional‐group tolerance, radical chemistry represents an ideal strategy for the synthesis of challenging complex non‐proteinogenic AAs. Moreover, the radical cross‐coupling allows introducing AA residue into drug scaffolds and natural compounds. In the present review, we wish to summarize and discuss all the reported to date methods of the asymmetric synthesis of AAs using radical chemistry by presenting a comprehensive account of the literature in this field going back to 1990. We especially emphasize on a radical chemistry approach and, exclusively, on stereoselective synthesis of various α‐, β‐, γ‐AAs and derivatives employing a different type of radical initiators starting from AIBN and organostannes and ending with powerful photoredox catalysis. Furthermore, the mechanism of the reported reactions will be discussed.magnified image

Yves chauvin (1930-2015).

Yves Chauvin passed away at the age of 84 on January 27, 2015. We have lost a remarkable man and a prominent scientist who made momentous contributions to the field of homogeneous catalysis. He received the Nobel Prize in Chemistry in 2005 jointly with Robert H. Grubbs and Richard R. Schrock for his discoveries relating to the mechanism of olefin metathesis, a reaction that is now applied in numerous fields, as well as in industry. His fundamental scientific understanding of processes and mechanisms, and his visionary insights inspired everyone around him. Chauvin was born to French parents in Menin (Belgium), near the French border. He graduated from the École Supérieure de Chimie Industrielle de Lyon (now the École Supérieure de Chimie Physique Électronique de Lyon), in 1957. Various circumstances prevented him from pursuing a doctoral degree, which he always regretted. He started his industrial career in process development at Progil Lyon in 1958, but he left the company two years later, eager to explore new fields and ideas. He subsequently joined the Institut Français du Pétrole, now IFP Energies nouvelles, in 1960, and remained loyal to it until his retirement in 1995. He was fascinated and inspired by a number of breakthroughs at that time, for example the work by Karl Ziegler and Giulio Natta on olefin polymerization, Günther Wilke and Borislav Bogdanović on nickel-catalyzed olefin dimerization, and Geoffrey Wilkinson on rhodium-catalyzed hydrogenation. Chauvin decided to focus his early research on coordination/organometallic chemistry and homogeneous catalysis with transition-metal complexes. This discipline was embryonic in France and not yet used in the oil industry, which relied essentially on heterogeneous catalysts. Chauvin soon became France’s foremost expert in homogeneous catalysis. Chauvin looked back at 1964 as a decisive year. Three discoveries, namely the heterogeneously catalyzed disproportionation of olefins reported by Robert L. Banks from Phillips Petroleum, the homogeneous polymerization of cyclopentene published by Natta, and the new metal–carbon bond, in the carbenes, described by Ernst Otto Fischer, which seemingly had nothing in common, led to Chauvin’s major breakthrough on metathesis. The mechanism rationalized by Chauvin was later acclaimed by the entire scientific community. Apart from his work on metathesis, Chauvin investigated a large number of catalytic reactions such as polymerization and oligomerization reactions, carbonylation, hydrogenation, isomerization, and CC coupling. He took a particular interest in asymmetric amino acid synthesis. Chauvin strongly believed that fundamental research was vital to applied research and vice versa. He was able to contribute to improving industrial processes while using them for inspiration. Industrial applications were indeed his prime focus, and his research laboratory work resulted in the development of two key industrial processes in the field of homogenous transition-metal-catalyzed olefin oligomerization for refining or for petrochemistry. Chauvin was an unusually creative and successful researcher. He had no doubt that teamwork throughout the whole chain was the key to success. His research findings are the basis for more than 100 industrial processes that have been licensed worldwide. Driven by curiosity, passionate for science, always an avid reader of the literature, Chauvin had the ability to bridge the gap between fields that ignored each other. In the early 1990s, his last discovery involved applying ionic liquids, which were used as electrolytes to extend the “electrochemical windows” of batteries, as solvents for catalysis. His findings paved the way for applications in various areas and sparked keen interest from academia and industry. This was the perfect illustration of how pure science can be applied to benefit both the economy and the environment. In addition to his Nobel Prize, Chauvin, who was a member of the French Académie des Sciences, received several other distinctions including the Carl Engler medal of the Deutsche Wissenschaftliche Gesellschaft für Erdöl, Erdgas und Kohle (DGKM) in 1994. He was appointed “Grand Officier” of the Ordre National du Mérite (French National Order of Merit) in 2005 and was elevated to the highest class of “Grand-Croix” on January 21, 2015. Chauvin was also unpretentious, approachable, and keen to provide sensitive, individual guidance. He was fond of younger people, PhD students, and postdocs, and advised and encouraged them to develop their own ideas. Chauvin continued to work in research until the end of his life. He will be remembered for his impressive expertise, relentless inspiration, inquisitive mind, and passion for fundamental and applied science, as well as his loyalty and modesty. We will treasure the memories of the times we were fortunate to share with him.

ENANTIOMERIC EXCESSES INDUCED IN AMINO ACIDS BY ULTRAVIOLET CIRCULARLY POLARIZED LIGHT IRRADIATION OF EXTRATERRESTRIAL ICE ANALOGS: A POSSIBLE SOURCE OF ASYMMETRY FOR PREBIOTIC CHEMISTRY

The discovery of meteoritic amino acids with enantiomeric excesses of the L-form (ee L) has suggested that extraterrestrial organic materials may have contributed to prebiotic chemistry and directed the initial occurrence of the ee L that further led to homochirality of amino acids on Earth. A proposed mechanism for the origin of ee L in meteorites involves an asymmetric photochemistry of extraterrestrial ices by UV circularly polarized light (CPL). We have performed the asymmetric synthesis of amino acids on achiral extraterrestrial ice analogs by VUV CPL, investigating the chiral asymmetry transfer at two different evolutionary stages at which the analogs were irradiated (regular ices and/or organic residues) and at two different photon energies (6.6 and 10.2 eV). We identify 16 distinct amino acids and precisely measure the L-enantiomeric excesses using the enantioselective GC × GC-TOFMS technique in five of them: α-alanine, 2,3-diaminopropionic acid, 2-aminobutyric acid, valine, and norvaline, with values ranging from ee L = –0.20% ± 0.14% to ee L = –2.54% ± 0.28%. The sign of the induced ee L depends on the helicity and the energy of CPL, but not on the evolutionary stage of the samples, and is the same for all five considered amino acids. Our results support an astrophysical scenario in which the solar system was formed in a high-mass star-forming region where icy grains were irradiated during the protoplanetary phase by an external source of CPL of a given helicity and a dominant energy, inducing a stereo-specific photochemistry.

Strategies for Asymmetric Synthesis of Amino Acids with γ,δ-Unsaturation

The amino acid is a fundamental molecule of life. They serve as building blocks for polypeptides and proteins, which are essential parts of all living systems and are involved in almost every proce...

Asymmetric Synthesis of Amino Acids by Dehydrogenative Coupling

Asymmetric Synthesis of Amino Acids by Dehydrogenative Coupling

Rapid asymmetric synthesis of amino acids via NiII complexes based on new fluorine containing chiral auxiliaries

New fluorine-containing chiral auxiliaries (S)-N-(2-benzoylphenyl)-1-(2-fluorobenzyl)-, (S)-N-(2-benzoylphenyl)-1-(3-fluorobenzyl)-, and (S)-N-(2-benzoylphenyl)-1-(4-fluorobenzyl)-pyrrolidine-2-carboxamide and their NiII complexes of Schiff bases with glycine and alanine have been synthesized. The greater efficiency of the complexes in terms of faster reaction rates and stereoselectivities in the asymmetric synthesis of (S)-α-amino acids has also been demonstrated.

ChemInform Abstract: Asymmetric Synthesis of Amino Acids by Catalytic Reduction of Azlactones of Substituted Acylaminoacrylic Acids. Part 25. Study of Reductive Aminolysis of 2-Phenyl- and 2-Methyl-δ2-oxazolin-5- ones (I) with the Chiral Catalytic System

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Asymmetric Synthesis of Amino Acids by Catalytic Reduction of Azlactones of Acylaminoacrylic Acids. Part 24. Reductive Aminolysis of 2-Methyl-4-benzylidene-δ2-oxazolin-5-one (I) with a Catalytic System Based on (S)-Phenylalanine Deriv

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Efficient Asymmetric Synthesis of Amino Acids Through Hydrogenation of the Didehydroamino Acid Residue in Cyclic Imino-Ester Derivatives.

Abstract The trisubstituted olefinic bond of chiral cyclic α,β-didehydroamino acid derivatives was hydrogenated in the presence of Pd/C with >95% diastereoface discrimination to give, after hydrolysis, the corresponding S-amino acids. The reduction of the double bond with L-selectride® does not change the orientation of diastereoface discrimination and the diastereoselectivity is still high.

ChemInform Abstract: Chemo-Enzymatic Asymmetric Synthesis of Amino Acids. Enantioselective Hydrolyses of 2-Phenyloxazolin-5-ones.

ChemInform Abstract: Chemo-Enzymatic Asymmetric Synthesis of Amino Acids. Enantioselective Hydrolyses of 2-Phenyloxazolin-5-ones.

ChemInform Abstract: Asymmetric Syntheses of Unnatural Amino Acids and Hydroxyethylene Peptide Isosteres

Unnatural and naturally occurring nonproteinogenic α-amino acids have become important building blocks for the synthesis of biologically active peptides and peptidomimetic drug molecules. The asymmetric synthesis of α-amino acids has therefore become quite important as an indispensable research tool in academic, government, and industrial laboratories, and methodologies have been reviewed extensively. The established methods for the asymmetric synthesis of amino acids can be divided into roughly six categories (1). (1) The highly stereoselective hydrogenation of chiral, nonracemic dehydro amino acid derivatives or the asymmetric hydrogenation of prochiral dehydro amino acid derivatives. Chiral glycine equivalents serve as useful α-amino acid templates undergoing homologation via carbon-carbon bond formation at the α-position through nucleophilic carbanion alkylation (2) or electrophilic carbocation substitution (3). In addition both nucleophilic amination (4) and electrophilic amination (5) of optically active carbonyl derivatives has very recently been developed. (6) Enzymatic and whole-cell-based syntheses have recently become more attractive in terms of substrate versatility, cost, and scale. All of these methods have their relative strengths and weaknesses; the optimum method for each individual application must still be considered on a case-by-case basis with respect to functionality, quantity desired, cost, and time. The focus of this chapter will illustrate the utility of chiral, nonracemic glycinates which are commercially available and can be manipulated in a variety of ways to access structurally diverse classes of α-amino acids.

ChemInform Abstract: Asymmetric Synthesis of Amino Acids by Rhodium and Ruthenium Catalysis

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Asymmetric Synthesis of Amino Acids with a Tetrasubstituted Carbon Center via Memory of Chirality

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Asymmetric Amino Acid Synthesis by the Asymmetric Alkylation of Glycine Derivatives with Chiral Spiro‐Type and Simplified Phase‐Transfer Catalysts

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Electroenzymatic strategies for deracemization, stereoinversion and asymmetric synthesis of amino acids

A combination of a selective enzymatic oxidation with an unselective electrochemical reduction step was applied for deracemization, stereoinversion and asymmetric synthesis of l-leucine (starting from racemic leucine, d-leucine or 4-methyl-2-oxovaleric acid) in a batch reactor. d-Amino acid oxidase ( d-AAO) from Trigonopsis variabilis was used as enzyme. Reaction conditions for the electrochemical and enzymatic reactions were investigated separately and finally combined to an electroenzymatic synthesis, yielding 3.5 mmol L −1 d −1 of l-leucine ( ee 91%).

Synthesis and Crystal Structure of 4‐Amino‐3‐fluorophenylboronic Acid

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis and crystal structure of 4-amino-3-fluorophenylboronic acid

Amino-3-fluorophenyl boronic acid has been synthesized from 4-bromo-2-fluoroaniline by protecting the amine group and then carrying out a lithium-bromine exchange, followed by addition of trimethyl borate and then acidic hydrolysis. We obtained a 47% yield. We also measured the X-ray crystal structure. This derivative has a relatively low boronic acid pKa value of 7.8 when acetylated or attached to acrylamide hydrogels. It also contains a pendant amine which facilitates attachment to polymers, for example. We are using this compound to construct glucose sensing materials that operates at the physiological pH of bodily fluids. © 2003 Published by Elsevier Ltd. There is a continuing interest in the synthesis of new boronic acid derivatives. This interest stems from the importance of boronic acids in the synthesis of biologi- cally active compounds, and the use of boronic acids themselves as pharmaceutical agents. In the area of synthetic chemistry, boronic acids have been widely used in Suzuki cross-coupling reactions, 1 Petasis reac- tion, 2 asymmetric synthesis of amino acids, 3 Diels- Alder reactions, 4 protection of diols, 5 selective reduction of aldehydes, 6 carboxylic acid activation, 7,8 and as reagents and starting materials in organic synthesis. 9

Asymmetric synthesis of amino acids by Cr(II) complexes of natural amino acids

Stoichiometric reduction of the C,N double bond of oxime precursors of α-amino acids was performed in aqueous media by Cr(II) complexes of natural amino acids. The reduction of oximes of α-ketophenylacetic, α-keto-β-phenylpropionic and α-ketopropionic acids proceeded up to >90% conversion and 2–30% enantiomeric excess. 1:2 complexes of Cr(II) with l-alanine, l-valine, l-aspartic acid, l-histidine and l-phenylalanine were used as reducing agents. The reduction of α-(oximino)phenylacetic acid showed increasing e.e. (and decreasing conversion) with increasing temperature.

Halo-substituted (S)-N-(2-benzoylphenyl)-1-benzylpyrolidine-2-carboxamides as new chiral auxiliaries for the asymmetric synthesis of (S)-α-amino acids

The synthesis of new chiral auxiliaries (S)-N-(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)-pyrrolidine-2-carboxamide (1a), (S)-N-(2-benzoylphenyl)-1-(pentafluorobenzyl)pyrrolidine-2-carboxamide (1b), and (S)-N-(2-benzoylphenyl)-1-(4-isopropoxytetrafluorobenzyl)pyrrolidine-2-carboxamide (1c) and their application in the asymmetric synthesis of amino acids using NiII complexes of their Schiff"s bases with alanine and glycine are described. Compound 1a is particularly appropriate for highly stereoselective synthesis of α-methyl-α-amino acids with high enatiomeric purity (ee >95%).