600-18-0Relevant articles and documents
Zn(II)-, Al(III)-, and Cu(II)-Catalyzed Decarboxylation of 2-Oxalopropionic Acid
Kubala, Gregory,Martell, Arthur E.
, p. 6602 - 6609 (1982)
Distributions of species formed by the coordination of 2-oxalopropionic acid by Zn(II), Al(III), and Cu(II) ions are presented, and kinetics of decarboxylation are discussed in terms of the species present in solution.Studies of initial rates of metal ion catalyzed decarboxylation of 2-oxalopropionic acid (H2L) show dependence on the degree of formation of the metal chelate (ML).Rate constants (kML) for the decarboxylation of ZnL, CuL, and AlL+ were found to be 18.2 x 10-3 s-1, 21.0 x 10-3 s-1, and 9.51 x 10-3 s-1, respectively.The equilibrium constants for ML(keto) ML(enol) were evaluated for the Zn(II) and Al(III) systems and rate constants (kKML) for the decarboxylation of the active keto forms of the Zn(II) and Al(III) chelates were found to be 31 x 10-3 s-1 and 79 x 10-3 s-1, respectively.The decarboxylation rate constant for the 2:1 Al(III) chelate, AlL2-, was determined to be 33.5 x 10-3 s-1.The keto-enol equilibrium constant -(enol)>/-(keto)> was evaluated, and the decarboxylation rate constant of AlL2-(keto) was calculated as 43 x 10-3 s-1.
Nuclear Magnetic Resonance Investigation of the Spontaneous Decarboxylation of 2-Oxalopropionic Acid. 2. Species in Solution
Kubala, Gregory,Martell, A. E.
, p. 7609 - 7615 (1981)
The kinetics of the spontaneous decarboxylation of 2-oxalopropionic acid (OPA) to the enolate intermediate of α-ketobutyric acid (AKBA) with subsequent ketonization, and β-deuteration via enolization, have been studied by NMR in aqueous solution at 31 deg C.The rate constants for the decarboxylation of the fully protonated, monoprotonated, and fully deprotonated species of OPA were found to be 1.67 * 10-5 s-1, 13.5 * 10-5 s-1, and 7.75 * 10-5 s-1, respectively.The rate constant for the ketonization of the intermediate was found to be 3.25 * 10-4 s-1 while the rate constant for the enolization of OPA was found to be 2.70 * 10-4 s-1.The ketonization and enolization processes exhibited specific acid catalysis and the second-order rate constants were found to be 1.60 * 10-1 M-1 s-1 and 1.20 * 10-1 M-1 s-1, respectively.The first pKa of OPA, involving the carboxyl adjacent to the keto function, was found to be 1.75, while the second pKa for the remaining carboxyl group was determined to be 4.18.In D2O the pK's were calculated as 2.38 and 4.50, respectively.Under the reaction conditions employed the hydrate species exists in appreciable concentrations at low pH while the concentration of the enol species was not significant.
Engineering methionine γ-lyase from Citrobacter freundii for anticancer activity
Raboni, Samanta,Revtovich, Svetlana,Demitri, Nicola,Giabbai, Barbara,Storici, Paola,Cocconcelli, Chiara,Faggiano, Serena,Rosini, Elena,Pollegioni, Loredano,Galati, Serena,Buschini, Annamaria,Morozova, Elena,Kulikova, Vitalia,Nikulin, Alexey,Gabellieri, Edi,Cioni, Patrizia,Demidkina, Tatyana,Mozzarelli, Andrea
, p. 1260 - 1270 (2018)
Methionine deprivation of cancer cells, which are deficient in methionine biosynthesis, has been envisioned as a therapeutic strategy to reduce cancer cell viability. Methionine γ-lyase (MGL), an enzyme that degrades methionine, has been exploited to selectively remove the amino acid from cancer cell environment. In order to increase MGL catalytic activity, we performed sequence and structure conservation analysis of MGLs from various microorganisms. Whereas most of the residues in the active site and at the dimer interface were found to be conserved, residues located in the C-terminal flexible loop, forming a wall of the active site entry channel, were found to be variable. Therefore, we carried out site-saturation mutagenesis at four independent positions of the C-terminal flexible loop, P357, V358, P360 and A366 of MGL from Citrobacter freundii, generating libraries that were screened for activity. Among the active variants, V358Y exhibits a 1.9-fold increase in the catalytic rate and a 3-fold increase in KM, resulting in a catalytic efficiency similar to wild type MGL. V358Y cytotoxic activity was assessed towards a panel of cancer and nonmalignant cell lines and found to exhibit IC50 lower than the wild type. The comparison of the 3D-structure of V358Y MGL with other MGL available structures indicates that the C-terminal loop is either in an open or closed conformation that does not depend on the amino acid at position 358. Nevertheless, mutations at this position allosterically affects catalysis.
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 (2021/06/30)
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.
Unusual stereoselectivity of methionine-γ-lyase from Citrobacterfreundii toward diastereomeric (S)-methionine S-oxide
Faleev, Nikolai G.,Tsvetikova, Marina A.,Ilyin, Mikhail M.,Yufryakov, Vyacheslav S.,Kolotyrkina, Natal'ya G.,Kulikova, Viktoria V.,Demidkina, Tatiana V.,Kochetkov, Konstantin A.
, p. 236 - 238 (2021/05/04)
Using a diastereomeric mixture of (S)-methionine S-oxide as an example, kinetic preference of methionine-γ-lyase toward a stereogenic center at the γ-sulfur atom of the (2S, RS) diastereomer was discovered for the first time.
Photoinduced homolytic decarboxylative acylation/cyclization of unactivated alkenes with α-keto acid under external oxidant and photocatalyst free conditions: access to quinazolinone derivatives
Sun, Bin,Shi, Rongcheng,Zhang, Kesheng,Tang, Xiaoli,Shi, Xiayue,Xu, Jiayun,Yang, Jin,Jin, Can
supporting information, p. 6050 - 6053 (2021/06/21)
A novel and green strategy for the synthesis of acylated quinazolinone derivativesviaphoto-induced decarboxylative cascade radical acylation/cyclization of quinazolinone bearing unactivated alkenes has been developed. The protocol provides a novel route to access acyl radicals from α-keto acids through a self-catalyzed energy transfer process. Most importantly, the reaction proceeded smoothly without any external photocatalyst, additive or oxidant, and could be easily scaled-up in flow conditions with sunlight irradiation.
Biocatalytic Cascade Reaction for the Asymmetric Synthesis of L- and D-Homoalanine
Silva, Marcus V. de M.,Costa, Ingrid C. R.,de Souza, Rodrigo O. M. A.,Bornscheuer, Uwe T.
, p. 407 - 411 (2018/11/01)
Unnatural amino acids attract growing attention for pharmaceutical applications as they are useful building blocks for the synthesis of a number of chiral drugs. Here, we describe a two-step enzymatic method for the asymmetric synthesis of homoalanine from L-methionine, a cheap and readily available natural amino acid. First, the enzyme L-methionine γ-lyase (METase), from Fusobacterium nucleatum, catalyzed the γ-elimination of L-methionine to 2-oxobutyrate. Second, an amino acid aminotransferase catalyzed the asymmetric conversion of 2-oxobutyrate to either L- or D-homoalanine. The L-branched chain amino acid aminotransferase from Escherichia coli (eBCAT), using L-glutamate as amino donor, produced L-homoalanine (32.5 % conv., 28 % y, 99 % ee) and the D-amino acid aminotransferase from Bacillus sp. (DATA) used D-alanine as amino donor to produce D-homoalanine (87.5 % conv., 69 % y, 90 % ee). Thus, this concept allows for the first time the synthesis of both enantiomers of this important unnatural amino acid.
Electrochemical synthesis of enaminones: Via a decarboxylative coupling reaction
Kong, Xianqiang,Liu, Yulong,Lin, Long,Chen, Qianjin,Xu, Bo
supporting information, p. 3796 - 3801 (2019/07/31)
An environmentally benign and efficient electrochemical synthesis of enaminones via a decarboxylative coupling reaction of α-keto acids using n-Bu4NI as a redox catalyst and electrolyte under constant current electrolysis in an undivided cell is reported. A broad vinyl azide substrate scope and high functional group tolerance are observed. A gram-scale reaction further demonstrates the practicability of the protocol. The results of cyclic voltammetry and control experiments indicate that I2 is likely the active species to initiate the oxidative decarboxylation via an acyl hypoiodite intermediate.
One-Pot Preparation of d-Amino Acids Through Biocatalytic Deracemization Using Alanine Dehydrogenase and Ω-Transaminase
Han, Sang-Woo,Shin, Jong-Shik
, p. 3678 - 3684 (2018/10/20)
d-Amino acids are pharmaceutically important building blocks, leading to a great deal of research efforts to develop cost-effective synthetic methods. Preparation of d-amino acids by deracemization has been conceptually attractive owing to facile synthesis of racemic amino acids by Strecker synthesis. Here, we demonstrated biocatalytic deracemization of aliphatic amino acids into d-enantiomers by running cascade reactions; (1) stereoinversion of l-amino acid to a d-form by amino acid dehydrogenase and ω-transaminase and (2) regeneration of NAD+ by NADH oxidase. Under the cascade reaction conditions containing 100?mM isopropylamine and 1?mM NAD+, complete deracemization of 100?mM dl-alanine was achieved after 24?h with 95% reaction yield of d-alanine (> 99% eeD, 52% isolation yield). Graphical Abstract: [Figure not available: see fulltext.].
Highly atom economic synthesis of D-2-aminobutyric acid through an in vitro tri-enzymatic catalytic system
Chen, Xi,Cui, Yunfeng,Cheng, Xinkuan,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
, p. 534 - 540 (2018/08/17)
D-2-Aminobutyric acid is an unnatural amino acid serving as an important intermediate in pharmaceutical production. Developing a synthetic method that uses cheaper starting materials and produces less by-product is a pressing demand. A tri-enzymatic catalytic system, which is composed of L-threonine ammonia lyase (L-TAL), D-amino acid dehydrogenase (D-AADH), and formate dehydrogenase (FDH), has thus been developed for the synthesis of D-2-aminobutyric acid with high optical purity. In this cascade reaction, the readily available L-threonine serves as the starting material, carbon dioxide and water are the by-products. D-2-Aminobutyric acid was obtained with >90% yield and >99% enantioselective excess, even without adding external ammonia, demonstrating that the ammonia from the first reaction can serve as the amino donor for the reductive amination step. This multi-enzymatic system provides an attractive method with high atomic economy for the synthesis of D-α-amino acids from the corresponding L-α-amino acids, which are readily produced by fermentation.
