6945-32-0Relevant articles and documents
Asymmetric α-arylation of amino acids
Leonard, Daniel J.,Ward, John W.,Clayden, Jonathan
, p. 105 - 109 (2018/10/15)
Quaternary amino acids, in which the α-carbon that bears the amino and carboxyl groups also carries two carbon substituents, have an important role as modifiers of peptide conformation and bioactivity and as precursors of medicinally important compounds1,2. In contrast to enantioselective alkylation at this α-carbon, for which there are several methods3–8, general enantioselective introduction of an aryl substituent at the α-carbon is synthetically challenging9. Nonetheless, the resultant α-aryl amino acids and their derivatives are valuable precursors to bioactive molecules10,11. Here we describe the synthesis of quaternary α-aryl amino acids from enantiopure amino acid precursors by α-arylation without loss of stereochemical integrity. Our approach relies on the temporary formation of a second stereogenic centre in an N′-arylurea adduct12 of an imidazolidinone derivative6 of the precursor amino acid, and uses readily available enantiopure amino acids both as a precursor and as a source of asymmetry. It avoids the use of valuable transition metals, and enables arylation with electron-rich, electron-poor and heterocyclic substituents. Either enantiomer of the product can be formed from a single amino acid precursor. The method is practical and scalable, and provides the opportunity to produce α-arylated quaternary amino acids in multi-gram quantities.
UNNATURAL AMINO ACIDS
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Paragraph 00190; 00296, (2018/07/05)
The present invention relates to a process for the preparation compounds of Formula (I): Formula (I) wherein X, Z, Q, Ar, R1, R2, R3 and R4 are each as defined herein. The present invention also relates to processes for the preparation of the compounds of quaternary amino acids and hydantions, to compound of Formula(I), to intermediate compounds of Formula (II), to quaternary amino acid compounds of Formula (III) and to hydantoin compounds of Formula (IV).
New enzymatic methods for the synthesis of primary α-aminonitriles and unnatural α-amino acids by oxidative cyanation of primary amines with d-amino acid oxidase from porcine kidney
Kawahara, Nobuhiro,Yasukawa, Kazuyuki,Asano, Yasuhisa
supporting information, p. 418 - 424 (2017/08/14)
Oxidation of amino groups in amines or amino acids activates the sp3 Cα-H bond to form imines, making the alpha carbon atom a preferable target for nucleophilic reagents such as cyanide. Therefore, we focused on the oxidase reaction for the production of primary α-aminonitriles via imines. d-Amino acid oxidase from porcine kidney (pkDAO) and l-amino acid oxidase from Crotalus atrox catalyzed the synthesis of 2-amino-2-cyano-3-phenylpropanoic acid from phenylalanine and potassium cyanide (KCN). Mutant pkDAO (Y228L/R283G) catalyzed the synthesis of racemic-2-methyl-2-phenylglycinonitrile from (R)-α-methylbenzylamine and KCN. Based on these results, we developed a new cascade reaction for the synthesis of unnatural α-amino acids from primary amines using mutant pkDAO and nitrilase AY487533. This is the first report of the enzymatic synthesis of primary α-aminonitriles and unnatural α-amino acids. These methods will contribute widely to the synthesis of primary α-aminonitriles and unnatural α-amino acids in aqueous systems.
