Catalytic Asymmetric Synthesis of α-Amino Acids

Nájera, Carmén; Sansano, José M.

doi:10.1021/cr050580o

Cited by 743 publications

(293 citation statements)

References 518 publications

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“…The novel imines 2h-j, which possess highly-activated ester moieties such as phenyl, trifluoroethyl, or hexafluoroisopropyl esters could be prepared by our strategy (entries 8-10). Furthermore, attempted reactions led to almost quantitative formation of desired imino imides 2k and l with high purity (entries 11,12). Surprisingly, even thioester 2m, susceptible to an oxidant, could be prepared without any problems (entry 13).…”

Section: Resultsmentioning

confidence: 99%

“…[7][8][9][10][11] These contexts evoke much interest of synthetic chemists in asymmetric synthesis of the structural unit. 12,13) Enabling easy access to diverse α-amino acids only by changing nucleophiles employed, Mannich-type reaction of α-imino ester has been widely utilized for the asymmetric synthesis. [14][15][16][17][18][19][20] Generally, condensation of glyoxalates and primary amines affords α-imino esters as the requisite substrate for Mannich-type reaction (Chart 1a); however, the glyoxalates are unstable, and suffer easy hydrolysis or polymerization at room temperature.…”

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confidence: 99%

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A Convenient Method for Preparation of α-Imino Carboxylic Acid Derivatives and Application to the Asymmetric Synthesis of Unnatural α-Amino Acid Derivative

Inokuma

Jichu

Nishida

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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We describe herein a manganese(IV) oxide-mediated oxidation of N-p-methoxyphenyl (PMP)-protected glycine derivatives for the synthesis of α-imino carboxylic acid derivatives. Using this methodology, utilization of unstable glyoxic acid derivatives was avoided. Furthermore, using this methodology we synthesized novel α-imino carboxylic acid derivatives such as α-imino phenyl ester, perfluoroalkyl etsers, imides, and thioester. The asymmetric Mannich reaction of those novel imine derivatives with 1,3-dicarbonyl compound is also described, and the novel α-imino imide gave improved chemical yield and stereoselectivity compared with those obtained by the use of the conventional α-imino ester-type substrate.Key words α-imino carboxylic acid derivative; heterogeneous oxidant; asymmetric organocatalysis; thiourea; unnatural α-amino acid Unnatural α-amino acids are often seen in varieties of biologically active compounds, 1-4) including pharmaceutics, and have been used as indispensable chiral building blocks for the synthesis of such active compounds.5,6) Additionally, increasing utilities of unnatural amino acids as a key structural element have also been shown in fields of chemical biology and asymmetric transformation.7-11) These contexts evoke much interest of synthetic chemists in asymmetric synthesis of the structural unit.12,13) Enabling easy access to diverse α-amino acids only by changing nucleophiles employed, Mannich-type reaction of α-imino ester has been widely utilized for the asymmetric synthesis.14-20) Generally, condensation of glyoxalates and primary amines affords α-imino esters as the requisite substrate for Mannich-type reaction (Chart 1a); however, the glyoxalates are unstable, and suffer easy hydrolysis or polymerization at room temperature. Additionally, high susceptibility of the resulting α-imino ester to silica gel has forced us to directly use the imino esters for the Mannich reaction without purification, thereby leading to difficulty in maintaining the reaction outcome. In this context, cross-dehydrogenative coupling (CDC) has been investigated for the synthesis of α-functionalized amino acids 21-23) (Chart 1b). The CDC protocol features oxidative preparation of α-imino ester from glycinates with the use of the oxidants such as 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), CuOAc, Ru(bpy) 3 Cl 2 / light (or N-oxyl radical), or Cu(I)/molecular oxygen, followed by in situ Mannich reaction. Although the CDC protocol is free from the use of unstable glyoxalates, the in situ Mannich reaction has to be performed in the presence of the employed oxidant due to difficulty in achieving complete separation of the imino ester and oxidant, by which the use of the CDC remains within application to the coupling of oxidant-tolerant functional units. Here, we envisioned that the heterogeneous oxidation system enabling facile removal of insoluble oxidants by filtration allowed the imino ester to be readily obtained and subsequently subjected to Mannich reaction under oxidant-free conditions (Chart 1c).

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Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

A Convenient Method for Preparation of α-Imino Carboxylic Acid Derivatives and Application to the Asymmetric Synthesis of Unnatural α-Amino Acid Derivative

Inokuma

Jichu

Nishida

et al. 2017

CHEMICAL & PHARMACEUTICAL BULLETIN

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“…The catalytic asymmetric Strecker reaction [3][4][5][6][7][8][9] has proved to be a simple and efficient method for the synthesis of optically pure α-amino acid derivatives. 10 Its development has been extremely fast since the first report of such a reaction appeared in 1996. 11 Therefore, the development of catalytic enantioselective Strecker reactions has been the focus of increasing attention in the field of asymmetric synthesis.…”

Section: Methodsmentioning

confidence: 99%

Recent advances on asymmetric Strecker reactions

Cai¹,

Xie²

2014

Arkivoc

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The Strecker reaction is one of the most attractive methods for the synthesis of α-amino acids and other bioactive compounds including natural products. The asymmetric Strecker reaction represents a simple and efficient method for the synthesis of optically pure α-amino acid derivatives, nucleic acids, various nitrogen and sulfur containing heterocycles and pharmaceuticals. Over the past several decades, considerable effort has been devoted towards the development of asymmetric Strecker reactions. This review provides an overview of recent asymmetric Strecker reactions, from diastereoselective reactions and catalytic enantioselective reactions including chiral catalytic metal systems and chiral organocatalytic systems.

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“…[1][2][3] In this context, azlactones (also known as oxazolones) are promising substrates, since they basically consist of protected amino acids organized as five-membered rings bearing both electrophilic and pronucleophilic sites in their structure. 4,5 Due to this versatility, these heterocycles have been extensively employed in a wide scope of transformations, 6 in particular the preparation of quaternary amino acid derivatives.…”

Section: Introductionmentioning

confidence: 99%

Brønsted Acid-Catalyzed Dipeptides Functionalization through Azlactones

Santos¹,

Castro²,

Almeida³

et al. 2017

J. Braz. Chem. Soc.

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Azlactones are useful building blocks in the synthesis of functional amino acid derivatives, heterocycles and bioactive molecules. In this work, a protocol for the organocatalytic functionalization of dipeptides has been presented. 2-Alkyl-substituted azlactone intermediates in the presence of different amines and alcohols were combined in a ring opening reaction approach. The products were synthesized in moderate to excellent isolated yields, providing new insights in peptide transformations involving carbodiimide activation.

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Catalytic Asymmetric Synthesis of α-Amino Acids

Cited by 743 publications

References 518 publications

A Convenient Method for Preparation of α-Imino Carboxylic Acid Derivatives and Application to the Asymmetric Synthesis of Unnatural α-Amino Acid Derivative

A Convenient Method for Preparation of α-Imino Carboxylic Acid Derivatives and Application to the Asymmetric Synthesis of Unnatural α-Amino Acid Derivative

Recent advances on asymmetric Strecker reactions

Brønsted Acid-Catalyzed Dipeptides Functionalization through Azlactones

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