2623-91-8Relevant articles and documents
Catalytic Asymmetric Hydrogenation of Dehydroamino Acid Esters with Biscarbamate Protection and Its Application to the Synthesis of xCT Inhibitors
Yasuno, Yoko,Mizutani, Iho,Sueuchi, Yuki,Wakabayashi, Yuuka,Yasuo, Nozomi,Shimamoto, Keiko,Shinada, Tetsuro
, p. 5145 - 5148 (2019)
Catalytic asymmetric hydrogenation of dehydroamino acid esters with biscarbamate protection was examined for the first time to prepare optically active amino acids. The new method was successfully applied to the synthesis of new cystine–glutamate exchanger inhibitors.
Novel intermolecular carbon radical addition to a nitrone: asymmetric synthesis of alpha-amino acids.
Ueda, Masafumi,Miyabe, Hideto,Teramachi, Masako,Miyata, Okiko,Naito, Takeaki
, p. 426 - 427 (2003)
A nitrone was used as a synthetically useful radical acceptor in carbon-carbon bond-forming radical reactions; the intermolecular addition of alkyl radicals to chiral glyoxylic nitrone was studied; a high degree of stereocontrol in radical addition to glyoxylic nitrone was achieved to provide a new method for asymmetric synthesis of alpha-amino acids.
Simultaneous Preparation of (S)-2-Aminobutane and d -Alanine or d -Homoalanine via Biocatalytic Transamination at High Substrate Concentration
Li, Jianjiong,Wang, Yingang,Wu, Qiaqing,Yao, Peiyuan,Yu, Shanshan,Zhu, Dunming
supporting information, (2022/03/01)
(S)-2-Aminobutane, d-alanine, and d-homoalanine are important intermediates for the production of various active pharmaceutical ingredients and food additives. The preparation of these small chiral amine or amino acids with high water solubility still demands searching for efficient methods. In this work, we identified an ω-transaminase (ω-TA) from Sinirhodobacter hungdaonensis (ShdTA) that catalyzed the kinetic resolution of racemic 2-aminobutane at a concentration of 800 mM using pyruvate as the amino acceptor, leading to the simultaneous isolation of enantiopure (S)-2-aminobutane and d-alanine in 46% and 90% yield, respectively. In addition, (S)-2-aminobutane (98% ee) and d-homoalanine (99% ee) were isolated in 45% and 93% yield, respectively, in the kinetic resolution of racemic 2-aminobutane at a concentration of 400 mM coupled with deamination of l-threonine by threonine deaminase. We thus developed a biocatalytic process for the practical synthesis of these valuable small chiral amine and d-amino acids.
Highly Stable Zr(IV)-Based Metal-Organic Frameworks for Chiral Separation in Reversed-Phase Liquid Chromatography
Jiang, Hong,Yang, Kuiwei,Zhao, Xiangxiang,Zhang, Wenqiang,Liu, Yan,Jiang, Jianwen,Cui, Yong
supporting information, p. 390 - 398 (2021/01/13)
Separation of racemic mixtures is of great importance and interest in chemistry and pharmacology. Porous materials including metal-organic frameworks (MOFs) have been widely explored as chiral stationary phases (CSPs) in chiral resolution. However, it remains a challenge to develop new CSPs for reversed-phase high-performance liquid chromatography (RP-HPLC), which is the most popular chromatographic mode and accounts for over 90% of all separations. Here we demonstrated for the first time that highly stable Zr-based MOFs can be efficient CSPs for RP-HPLC. By elaborately designing and synthesizing three tetracarboxylate ligands of enantiopure 1,1′-biphenyl-20-crown-6, we prepared three chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2]. They share the same flu topological structure but channels of different sizes and display excellent tolerance to water, acid, and base. Chiral crown ether moieties are periodically aligned within the framework channels, allowing for stereoselective recognition of guest molecules via supramolecular interactions. Under acidic aqueous eluent conditions, the Zr-MOF-packed HPLC columns provide high resolution, selectivity, and durability for the separation of a variety of model racemates, including unprotected and protected amino acids and N-containing drugs, which are comparable to or even superior to several commercial chiral columns for HPLC separation. DFT calculations suggest that the Zr-MOF provides a confined microenvironment for chiral crown ethers that dictates the separation selectivity.
Zelkovamycins B-E, Cyclic Octapeptides Containing Rare Amino Acid Residues from an Endophytic Kitasatospora sp
Cen, Shan,Connolly, Jack A.,Gan, Maoluo,Goss, Rebecca J. M.,Hao, Xiaomeng,Liu, Yufeng,Wang, Yujia,Yu, Jiaqing,Yu, Liyan,Zhang, Yuqin
, p. 9346 - 9350 (2020/12/21)
Four unusual cyclopeptides, zelkovamycins B-E (1-4), were isolated from an endophytic Kitasatospora sp. Zelkovamycin B was featured by an unprecedented 3-methyl-5-hydroxypyrrolidine-2,4-dione ring system linked to the cyclopeptide skeleton. Their structures and full configurations were established by spectroscopic analysis, Marfey's method, and NMR calculations. A plausible biosynthetic pathway for zelkovamycins was proposed based on gene cluster analysis. Zelkovamycin E displayed potent inhibitory activity against H1N1 influenza A virus.
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.
Enantioselective Synthesis of d- and l-α-Amino Acids by Enzymatic Transamination Using Glutamine as Smart Amine Donor
Heuson, Egon,Charmantray, Franck,Petit, Jean-Louis,de Berardinis, Véronique,Gefflaut, Thierry
supporting information, p. 778 - 785 (2019/01/04)
Enzymatic transamination is a useful method for the green and highly enantioselective synthesis of chiral amines and non-canonical amino acids which are of major importance as intermediates in medicinal chemistry. However, transamination reactions are usually reversible and synthetic applications of transaminases often require the implementation of an equilibrium shift strategy. Herein, we report a highly effective approach using glutamine as smart amine donor. This amino acid is converted upon transamination into 2-oxoglutaramate which undergoes a fast cyclisation displacing the transamination equilibrium. We have developed a new activity assay in order to identify transaminases from biodiversity able to convert various α-keto acids into valuable amino acids of l- or d-series in the presence of glutamine as amine donor. Discovered transaminases were then used to prepare in high yield and with high enantioselectivity three amino acids of pharmaceutical importance, homophenylalanine, homoalanine and tert-leucine by simply using a nearly stoichiometric amount of glutamine as amine donor. (Figure presented.).
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.].
Structure-guided engineering of: Meso -diaminopimelate dehydrogenase for enantioselective reductive amination of sterically bulky 2-keto acids
Cheng, Xinkuan,Chen, Xi,Feng, Jinhui,Wu, Qiaqing,Zhu, Dunming
, p. 4994 - 5002 (2018/10/17)
meso-Diaminopimelate dehydrogenase (DAPDH) and mutant enzymes are an excellent choice of biocatalysts for the conversion of 2-keto acids to the corresponding d-amino acids. However, their application in the enantioselective reductive amination of bulky 2-keto acids, such as phenylglyoxylic acid, 2-oxo-4-phenylbutyric acid, and indole-3-pyruvic acid, is still challenging. In this study, the structure-guided site-saturation mutagenesis of a Symbiobacterium thermophilum DAPDH (StDAPDH) gave rise to a double-site mutant W121L/H227I, which showed dramatically improved enzyme activities towards various 2-keto acids including these sterically bulky substrates. Several d-amino acids were prepared in optically pure form. The molecular docking of substrates into the active sites of wild-type and mutant W121L/H227I enzymes revealed that the substrate binding cavity of the mutant enzyme was reshaped to accommodate these bulky substrates, thus leading to higher enzyme activity. These results lay a foundation for further shaping the substrate binding pocket and manipulating the interactions between the substrate and binding sites to access highly active d-amino acid dehydrogenases for the preparation of synthetically challenging d-amino acids.
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.
