1012-05-1Relevant articles and documents
Rational engineering ofAcinetobacter tandoiiglutamate dehydrogenase for asymmetric synthesis ofl-homoalanine through biocatalytic cascades
Diao, Shiqing,Jiang, Shuiqin,Liu, Yan,Sun, Yangyang,Wang, Hualei,Wang, Liuzhu,Wei, Dongzhi
, p. 4208 - 4215 (2021)
l-Homoalanine, a useful building block for the synthesis of several chiral drugs, is generally synthesized through biocascades using natural amino acids as cheap starting reactants. However, the addition of expensive external cofactors and the low efficiency of leucine dehydrogenases towards the intermediate 2-ketobutyric acid are two major challenges in industrial applications. Herein, a dual cofactor-dependent glutamate dehydrogenase fromAcinetobacter tandoii(AtGluDH) was identified to help make full use of the intracellular pool of cofactors when using whole-cell catalysis. Through reconstruction of the hydrophobic network between the enzyme and the terminal methyl group of the substrate 2-ketobutyric acid, the strict substrate specificity ofAtGluDH towards α-ketoglutarate was successfully changed, and the activity obtained by the most effective mutant (K76L/T180C) was 17.2 times higher than that of the wild-type protein. A three-enzyme co-expression system was successfully constructed in order to help release the mass transfer restriction. Using 1 Ml-threonine, which is close to the solubility limit, we obtained a 99.9% yield ofl-homoalanine in only 3.5 h without adding external coenzymes to the cascade, giving 99.9% ee and a 29.2 g L?1h?1space-time yield. Additionally, the activities of the engineeredAtGluDH towards some other hydrophobic amino acids were also improved to 1.1-11.2 fold. Therefore, the engineering design of some dual cofactor-dependent GluDHs could not only eliminate the low catalytic activity of unnatural substrates but also enhance the cofactor utilization efficiency of these enzymes in industrial applications.
Enzymatic resolution of N-acetyl-homophenylalanine with mammalian kidney acetone powders
Regla, Ignacio,Luna, Hector,Perez, Herminia I.,Demare, Patricia,Bustos-Jaimes, Ismael,Zaldivar, Victor,Calcagno, Mario L.
, p. 1285 - 1288 (2004)
Kidney acetone powders (KAP) from beef, dog, hog, rat, and sheep have been evaluated for resolving N-acetyl-DL-homophenylalanine. We also propose a simple protocol for the preparation of both enantiomers of homophenylalanine by enzymatic resolution using mammalian KAP. The beef kidney afforded the best results, rendering the highest isolated yields, 37.5% and 41% and enantiomeric excesses of 94% and 99% for both D-N-Ac-homophenylalanine and L-homophenylalanine, respectively.
One-pot, two-step synthesis of unnatural α-amino acids involving the exhaustive aerobic oxidation of 1,2-diols
Inada, Haruki,Furukawa, Keisuke,Shibuya, Masatoshi,Yamamoto, Yoshihiko
, p. 15105 - 15108 (2019)
Herein, we report the nor-AZADO-catalyzed exhaustive aerobic oxidations of 1,2-diols to α-keto acids. Combining oxidation with transamination using dl-2-phenylglycine led to the synthesis of free α-amino acids (AAs) in one pot. This method enables the rapid and flexible preparation of a variety of valuable unnatural AAs, such as fluorescent AAs, photoactivatable AAs, and other functional AAs for bioorthogonal reactions.
Synthesis of Unprotected 2-Arylglycines by Transamination of Arylglyoxylic Acids with 2-(2-Chlorophenyl)glycine
Inada, Haruki,Shibuya, Masatoshi,Yamamoto, Yoshihiko
, p. 11047 - 11059 (2020/10/12)
The transamination of α-keto acids with 2-phenylglycine is an effective methodology for directly synthesizing unprotected α-amino acids. However, the synthesis of 2-arylglycines by transamination is problematic because the corresponding products, 2-arylglycines, transaminate the starting arylglyoxylic acids. Herein, we demonstrate the use of commercially available l-2-(2-chlorophenyl)glycine as the nitrogen source in the transamination of arylglyoxylic acids, producing the corresponding 2-arylglycines without interference from the undesired self-transamination process.
Direct Synthesis of Free α-Amino Acids by Telescoping Three-Step Process from 1,2-Diols
Inada, Haruki,Shibuya, Masatoshi,Yamamoto, Yoshihiko
supporting information, p. 709 - 713 (2019/01/25)
A practical telescoping three-step process for the syntheses of α-amino acids from the corresponding 1,2-diols has been developed. This process enables the direct synthesis of free α-amino acids without any protection/deprotection step. This method was also effective for the preparation of a 15N-labeled α-amino acid. 1,2-Diols bearing α,β-unsaturated ester moieties afforded bicyclic α-amino acids through intramolecular [3 + 2] cycloadditions. A preliminary study suggests that the resultant α-amino acids are resolvable by aminoacylases with almost complete selectivity.
Copper-Catalyzed Addition of Alkylboranes to Iminoacetates: Access to α-Alkyl Branched α-Amino Acids
Xiao, Xinsheng,Zhang, Wei,Lu, Xiaoxia,Deng, Yuanfu,Jiang, Huangfeng,Zeng, Wei
, p. 2497 - 2509 (2016/08/16)
A copper(I)-catalyzed addition of alkylborane reagents to α-iminoacetates has been developed to assemble both acyclic and cyclic α-branched α-amino carboxylic acid derivatives in good yields. A wide variety of unactivated alkenes are well tolerated in this transformation. (Figure presented.).
Total synthesis of amiclenomycin, an inhibitor of biotin biosynthesis.
Mann, Stephane,Carillon, Sophie,Breyne, Olivier,Marquet, Andree
, p. 439 - 450 (2007/10/03)
We describe the first synthesis of amiclenomycin, a natural product that has been found to inhibit biotin biosynthesis and, as a consequence, to exhibit antibiotic properties. Structure 1, with a trans relationship between the ring substituents. had previously been proposed for amiclenomycin on the basis of its 1H NMR spectrum. We have prepared the trans and cis isomers 1 and 2 by unequivocal routes and we conclude that the natural product is in fact the cis isomer 2. The properly substituted cyclohexadienyl rings were constructed first. A cycloaddition reaction between 1,2-di(phenylsulfonyl)ethylene and the N-allyloxycarbonyl diene 13, followed by reductive elimination of the phenylsulfinyl groups, gave the cis isomer 15. To obtain the trans isomer, the O-trimethylsilyl diene was used to give the cis hydroxylated Diels-Alder adduct 33, which was transformed into the corresponding trans amino derivative by means of a Mitsunobu reaction. The L-alpha-amino acid functionality was introduced by means of a Strecker reaction on the aldehydes 16 and 42, followed by enzymatic hydrolysis with immobilised pronase.
Synthesis of [1-13C] and [1-15N] labelled DL-homophenylalanine via a key Neber rearrangement
Oldfield, Mark F.,Botting, Nigel P.
, p. 29 - 36 (2007/10/03)
A synthetic route involving a key Neber rearrangement is described for the preparation of both [1-13C] and [1-15N] DL-homophenylalanine (2- amino-4-phenylbutanoic acid), using suitably labelled sodium cyanide as the source of the isotopic label. These compounds have been prepared for use in studies on the biosynthesis of phenylethyl glucosinolate in Brassica napus. 3-Phenylpropanaldoxime, the initial biosynthetic product formed from homophenylalanine, was also prepared in 15N labelled form.
Studies on Angiotensin Converting Enzyme Inhibitors. 4. Synthesis and Angiotensin Converting Enzyme Inhibitory Activities of 3-Acyl-1-alkyl-2-oxoimidazolidine-4-carboxylic Acid Derivatives
Hayashi, Kimiaki,Nunami, Ken-ichi,Kato, Jyoji,Yoneda, Naoto,Kubo, Masami,et al.
, p. 289 - 297 (2007/10/02)
(4S)-1-Alkyl-3-acyl>-2-oxoimidazolidine-4-carboxylic acid derivatives (3) were prepared by two methods.Their angiotensin converting enzyme (ACE) inhibitory activities and antihypertensive effects were evaluated, and the structure-activity relationships were discussed.The dicarboxylic acids 3a-n possessing S,S,S configuration showed potent in vitro ACE inhibitory activities with IC 50 values of 1.1x10-8-1.5x10-9 M.The most potent compound in this series, monoester 3p, had an ID 50 value of 0.24 mg/kg, po for inhibition of angiotensin I induced pressor response in normotensive rats and produced a dose-dependent decrease in systolic blood pressure of spontaneously hypertensive rats (SHRs) at doses of 1-10 mg/kg, po.
