25608-40-6Relevant articles and documents
On the ingredients of the green amanita. XXVI. The building elements of gamma-amanitine
Wieland,Wehrt
, p. 120 - 125 (1966)
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NEW CHIRAL SYNTHON OF ELECTROPHILIC GLYCINE AND ITS REACTIONS WITH METALLOORGANIC, C-H, N-H, AND O-H COMPOUNDS FOR THE ASYMMETRIC SYNTHESIS OF α-SUBSTITUTED α-AMINOACIDS
Belokon', Yu. N.,Popkov, A. N.,Chernoglazova, N. I.,Bakhmutov, V. I.,Saporovskaya, M. B.,Belikov, V. M.
, p. 1744 - 1748 (1989)
A new chiral synthon of the electrophilic glycine - the Ni(II) complex of the Schiff base of L-N-benzylprolylorthoaminobenzophenone with α-bromoglycine - was synthesized.The reaction of this complex with nucleophiles led to the isolation of complexes of L- and D-2-amino-2-dimethylaminoacetic acid, L- and D-2-amino-2-phenoxyacetic acid, 3,3-di(carbethoxy)alanine, and norleucine.The decomposition of the 3,3-di(carbethoxy)alanine and norleucine complexes led to the synthesis of L-aspartic acid and L-norleucine with the enantiomeric purity of 80 and 68 percent correspondingly.
Stability of L-asparaginase: An enzyme used in leukemia treatment
Stecher,Morgantetti De Deus,Polikarpov,Abrahao-Neto
, p. 1 - 9 (1999)
L-asparaginase from Escherichia coli is an important enzyme widely used in leukemia treatment under the trade name Elspar. Up to now, however, the aspects of its stability and storage has not been studied in detail. The aim of this work is to analyze the factors that could interfere in the enzyme's stability. The enzymatic activity was found to be stable in wide pH range (4.5-11.5), showing a slight increase in activity and stability in alkaline pHs, which indicates a more stable conformation of the molecule. The enzyme proved to have a high activity restoration capacity when submitted to temperatures of 65°C, in pH 8.6 buffer and, surprisingly, in physiologic solution. This suggests a positive effect of sodium ions on such restoration capacity. Stability was high in different diluents used as parenteral solutions and in recipients used in medical practice without significant loss of activity for at least 7 days. These results lead us to conclude that the enzyme has a high stability after the lyophilized form has been reconstituted (at least 7 days), since the necessary precautions are taken in terms of sterile manipulation and if it is stored in a suitable parenteral vehicle under low temperature (about 8°C). Copyright (C) 1999 Elsevier Science B.V.
Engineering methylaspartate ammonia lyase for the asymmetric synthesis of unnatural amino acids
Raj, Hans,Szymanski, Wiktor,De Villiers, Jandre,Rozeboom, Henriette J.,Veetil, Vinod Puthan,Reis, Carlos R.,De Villiers, Marianne,Dekker, Frank J.,De Wildeman, Stefaan,Quax, Wim J.,Thunnissen, Andy-Mark W.H.,Feringa, Ben L.,Janssen, Dick B.,Poelarends, Gerrit J.
, p. 478 - 484 (2012)
The redesign of enzymes to produce catalysts for a predefined transformation remains a major challenge in protein engineering. Here, we describe the structure-based engineering of methylaspartate ammonia lyase (which in nature catalyses the conversion of 3-methylaspartate to ammonia and 2-methylfumarate) to accept a variety of substituted amines and fumarates and catalyse the asymmetric synthesis of aspartic acid derivatives. We obtained two single-active-site mutants, one exhibiting a wide nucleophile scope including structurally diverse linear and cyclic alkylamines and one with broad electrophile scope including fumarate derivatives with alkyl, aryl, alkoxy, aryloxy, alkylthio and arylthio substituents at the C2 position. Both mutants have an enlarged active site that accommodates the new substrates while retaining the high stereo- and regioselectivity of the wild-type enzyme. As an example, we demonstrate a highly enantio- and diastereoselective synthesis of threo-3-benzyloxyaspartate (an important inhibitor of neuronal excitatory glutamate transporters in the brain).
The concept of internal solubilization in peptide synthesis: ethylene glycol-based protecting groups
Kocsis, László,Bruckdorfer, Thomas,Orosz, Gy?rgy
, p. 7015 - 7017 (2008)
A novel, ethylene glycol-based protecting group is designed and synthesized for use in solid phase peptide synthesis. Ether and ester type protected amino acids are prepared. The acid stability of the new protecting group showed complete Fmoc/t-Bu compatibility. The new derivatives are tested in solid phase peptide synthesis, with a 'difficult' sequence to examine the disruption of peptide aggregation.
SYNTHESIS OF D,L-β-CARBOXYASPARTIC ACID FROM HYDANTOIN-5-MALONIC ACID DIETHYL ESTER
Henson, Edward B.,Gallop, Paul M.,Hauschka, Peter V.
, p. 2561 - 2562 (1981)
Hydantoin-5-malonic acid diethyl ester was synthesized by reduction of parabanic acid (oxalyl urea) to 5-hydroxy-hydantoin, conversion to 5-chlorohydantoin and condensation with malonic ester.Alkaline hydrolysis gave D,L-β-carboxyaspartic acid.
Biocatalytic enantioselective synthesis of N-substituted aspartic acids by aspartate ammonia lyase
Weiner, Barbara,Poelarends, Gerrit J.,Janssen, Dick B.,Feringa, Ben L.
, p. 10094 - 10100 (2008)
The gene encoding aspartate ammonia lyase (asp B) from Bacillus sp. YM55-1 has been cloned and over-expressed, and the recombinant enzyme containing a C-terminal HiS6 tag has been purified to homogeneity and subjected to kinetic characterization. Kinetic studies have shown that the HiS6 tag does not affect AspB activity. The enzyme processes L-aspartic acid, but not D-aspartic acid, with a km of ≈15 mM and a Kcat, of ≈ 40s-1. By using this recombinant enzyme in the reverse reaction, a set of four N-substituted aspartic acids were prepared by the Michael addition of hydroxylamine, hydrazine, methoxylamine, and methylamine to fumarate. Both hydroxylamine and hydrazine were found to be excellent substrates for AspB. The kcat values are comparable to those observed for the AspB-catalyzed addition of ammonia to fumarate (≈90 s-1), whereas the Km values are only slightly higher. The products of the enzyme-catalyzed addition of hydrazine, methoxylamine, and methylamine to fumarate were isolated and characterized by NMR spectroscopy and HPLC analysis, which revealed that AspB catalyzes all the additions with excellent enantioselectivity (>97% ee). Its broad nucleophile specificity and high catalytic activity make AspB an attractive enzyme for the enantioselective synthesis of N-substituted aspartic acids, which are interesting building blocks for peptide and pharmaceutical synthesis as well as for peptidomimetics.
An enzymatic method for the kinetic measurement of L-asparaginase activity and l-asparagine with an ammonia gas-sensing electrode
Tagami,Matsuda
, p. 153 - 155 (1990)
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Talley et al.
, p. 174 (1959)
Modification of cellulose acetates for preparing chiral sorbents
Shipovskaya,Gegel',Shchegolev
, p. 1326 - 1333 (2014)
Modification of cellulose acetates via sorption-desorption of vapors of mesogenic solvents in which the polymer forms a lyotropic liquid crystal phase and of mixtures of these solvents with water leads to the formation of a new chiral structure of the polymeric sample. This is manifested in a significant change in the value and even sign of the specific optical rotation of the polysaccharide system. The sorbents based on cellulose acetates that have been modified by such treatment exhibit specific affinity for definite optical antipodes. When a racemic mixture of L- and D-isomers of amino acids is passed through this sorbent, it acts as a chiral filter owing to "steric recognition" of one of the enantiomers, so that the filtrate contains an optically pure product (isomer). The revealed effects served as a basis for the development of a new procedure for preparation of optically pure stereoisomers of chiral products.
Recreating the natural evolutionary trend in key microdomains provides an effective strategy for engineering of a thermomicrobial N-demethylase
Gu, Zhenghua,Guo, Zitao,Shao, Jun,Shen, Chen,Shi, Yi,Tang, Mengwei,Xin, Yu,Zhang, Liang
, (2022/03/09)
N-demethylases have been reported to remove the methyl groups on primary or secondary amines, which could further affect the properties and functions of biomacromolecules or chemical compounds; however, the substrate scope and the robustness of N-demethylases have not been systematically investigated. Here we report the recreation of natural evolution in key microdomains of the Thermomicrobium roseum sarcosine oxidase (TrSOX), an N-demethylase with marked stability (melting temperature over 100 C) and enantioselectivity, for enhanced substrate scope and catalytic efficiency on -C-N-bonds. We obtained the structure of TrSOX by crystallization and X-ray diffraction (XRD) for the initial framework. The natural evolution in the nonconserved residues of key microdomains—including the catalytic loop, coenzyme pocket, substrate pocket, and entrance site—was then identified using ancestral sequence reconstruction (ASR), and the substitutions that accrued during natural evolution were recreated by site-directed mutagenesis. The single and double substitution variants catalyzed the N-demethylation of N-methyl-L-amino acids up to 1800- and 6000-fold faster than the wild type, respectively. Additionally, these single substitution variants catalyzed the terminal N-demethylation of non-amino-acid compounds and the oxidation of the main chain -C-N- bond to a -C=N- bond in the nitrogen-containing heterocycle. Notably, these variants retained the enantioselectivity and stability of the initial framework. We conclude that the variants of TrSOX are of great potential use in N-methyl enantiomer resolution, main-chain Schiff base synthesis, and alkaloid modification or degradation.
Noncovalently Functionalized Commodity Polymers as Tailor-Made Additives for Stereoselective Crystallization
Wan, Xinhua,Wang, Zhaoxu,Ye, Xichong,Zhang, Jie
supporting information, p. 20243 - 20248 (2021/08/09)
Stereoselective inhibition of the nucleation and crystal growth of one enantiomer aided by “tailor-made” polymeric additives is an efficient method to obtain enantiopure compounds. However, the conventional preparation of polymeric additives from chiral monomers are laborious and limited in structures, which impedes their rapid optimization and applicability. Herein, we report a “plug-and-play” strategy to facilitate synthesis by using commercially available achiral polymers as the platform to attach various chiral small molecules as the recognition side-chains through non-covalent interactions. A library of supramolecular polymers made up of two vinyl polymers and six small molecules were applied with seeds in the selective crystallization of seven racemates in different solvents. They showed good to excellent stereoselectivity in yielding crystals with high enantiomeric purities in conglomerates and racemic compound forming systems. This convenient, low-cost modular synthesis strategy of polymeric additives will allow for high-efficient, economical resolution of various racemates on different scales.
