5380-36-9Relevant academic research and scientific papers
Substrate specificity determinants of the methanogen homoaconitase enzyme: Structure and function of the small subunit
Jeyakanthan, Jeyaraman,Drevland, Randy M.,Gayathri, Dasara Raju,Velmurugan, Devadasan,Shinkai, Akeo,Kuramitsu, Seiki,Yokoyama, Shigeyuki,Graham, David E.
, p. 2687 - 2696 (2010)
The aconitase family of hydro-lyase enzymes includes three classes of proteins that catalyze the isomerization of a-hydroxy acids to β-hydroxy acids. Besides aconitase, isopropylmalate isomerase (IPMI) proteins specifically catalyze the isomerization of α,β-dicarboxylates with hydrophobic y-chain groups, and homoaconitase (HACN) proteins catalyze the isomerization of tricarboxylates with variable chain length y-carboxylate groups. These enzymes' stereospecific hydro-lyase activities make them attractive catalysts to produce diastereomers from unsaturated precursors. However, sequence similarity and convergent evolution among these proteins lead to widespread misannotation and uncertainty about gene function. To find the substrate specificity determinants of homologous IPMI and HACN proteins from Methanocaldococcus jannaschii, the small-subunit HACN protein (MJ1271 ) was crystallized for X-ray diffraction. The structural model showed characteristic residues in a flexible loop region between α2 and α3 that distinguish HACN from IPMI and aconitase proteins. Site-directed mutagenesis of MJ1271 produced loop-region variant proteins that were reconstituted with wild-type MJ1003 large-subunit protein. The heteromers formed promiscuous hydro-lyases with reduced activity but broader substrate specificity. Both R26K and R26V variants formed relatively efficient IPMI enzymes, while the T27A variant had uniformly lower specificity constants for both IPMI and HACN substrates. The R26V T27Y variant resembles the MJ1277IPMI small subunit in its flexible loop sequence but demonstrated the broad substrate specificity of the R26V variant. These mutations may reverse the evolution of HACN activity from an ancestral IPMI gene, demonstrating the evolutionary potential for promiscuity in hydro-lyase enzymes. Understanding these specificity determinants enables the functional reannotation of paralogous HACN and IPMI genes in numerous genome sequences. These structural and kinetic results will help to engineer new stereospecific hydro-lyase enzymes for chemoenzymatic syntheses.
The sex pheromone of the wasp spider Argiope bruennichi
Chinta, Satya P.,Goller, Stephan,Lux, Julia,Funke, Sebastian,Uhl, Gabriele,Schulz, Stefan
supporting information; experimental part, p. 2033 - 2036 (2010/06/20)
(Figure Presented) Wasp spider looking for a mate: Female wasp spiders (see picture) use trimethyl methylcitrate as a volatile cue to attract males. The experiments were performed on a sunny meadow, showing for the first time that spider traps can be used to trap spiders in the field (photo: Helen Sandford).
N-HYDROXYAMIDE DERIVATIVES AND USE THEREOF
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Page/Page column 93-94, (2008/06/13)
The present invention is related to N-hydroxyamide derivatives of Formula (I) and use thereof, in particular for the treatment and/or prophylaxis of autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, cancer, respiratory diseases and fibrosis, including multiple sclerosis, arthritis, emphysema, chronic obstructive pulmonary disease, liver and pulmonary fibrosis.
Preparation of Both Enantiomers of Malic and Citramalic Acid and Other Hydroxysuccinic Acid Derivatives by Stereospecific Hydrations of cis or trans 2-Butene-1,4-dioic Acids with Resting Cells of Clostridium formicoaceticum
Eck, Richard,Simon, Helmut
, p. 13641 - 13654 (2007/10/02)
(R)-Malic, (S)-malic, (R)-citramalic, (S)-citramalic, (2R,3S)-2-hydroxy-3-methylsuccinic and (2R,3S)-2,3-dimethyl-2-hydroxysuccinic acid were prepared on scales up to 25 mmol by stereospecific addition of water to different 2-butene-1,4-dioic acid derivatives catalyzed by resting cells of Clostridium formicoaceticum (Scheme 1).The (3R)-monodeuterio (R)- and (S)-malic acid as well as (R)- and (S)-citramalic acid were prepared using freeze-dried cells in 2H2O-buffer.The stereochemical purity of the products was in most cases >/= 99percent.
Enantioselective Synthesis of (2R,3S)-3-Alkylmalic Acids, Competent Substrates for 3-Isopropylmalate Dehydrogenase
Kakinuma, Katsumi,Terasawa, Hiroaki,Li, Hui-Ying,Miyazaki, Kentaro,Oshima, Tairo
, p. 1916 - 1923 (2007/10/02)
A series of (2R,3S)-3-alkylmalic acids was enantioselectively synthesized, in conjunction with biochemical studies on the thermostable isopropylmalate dehydrogenase derived from Thermus thermophilus, by the chirality transcription approach, using a conceptually recyclable carbohydrate template.The dianion -Wittig rearrangement of alkylated allyloxyacetic acids prepared from alkylallyl tertiary-carbinols was effective in both reactivity and stereoselectivity to afford the desired diastereomers in a high yield.The derived γ,δ-unsaturated α-hydroxycarboxylic acids were oxidatively transformed into the desired (2R,3S)-3-alkylmalic acid derivatives.
On the Stereochemistry of E'- and E''-Reactions
Vogel, Ernst,Caravatti, Giorgio,Franck, Peter,Aristoff, Paul,Moody, Christopher,et al.
, p. 219 - 222 (2007/10/02)
The decarboxylative E'-dehydration of β,γ-unsaturated δ-hydroxy acids with DMF-dineopentylacetal shows SYN-faciality irrespective of whether the conformation of the hydroxy group relative to the double bond axis is anticlinal or synclinal.
Electrochemical Oxidation of (S)-Malic-Acid Derivatives: a Route to Enantiomerically Pure Alkylmalonaldehydic Esters
Renaud, Philippe,Muerzeler, Marianne,Seebach, Dieter
, p. 292 - 298 (2007/10/02)
The 3,3-dialkylmalic-acid diesters, prepared by the previously described diastereoselective alkylations through dilithium alkoxide enolates, are saponified to the monoesters containing a free α-hydroxycarboxylic-acid moiety.The monoesters are subjected to electrochemical oxidative decarboxylation in MeOH.If the intermediate monoacids are purified, the malonaldehydic esters (2-formyl-2-alkoxycarboxylates) obtained by this procedure are enantiomerically pure; they have the same structural features, i.e. two enantiotopic functionalized branches on the (persubstituted) stereogenic center, as the well known 3-hydroxy-2-methylpropanoic acid ('Roche acid') which was employed frequently as a starting material for the preparation of either enantiomer of various target molecules.
Synthesis of erythro-2-Hydroxy-3-methylbutane-1,4-dioic Acid
Bhat, K. S.,Dixit, K. N.,Rao, A. S.
, p. 509 - 512 (2007/10/02)
Reduction of ethyl 3-methyl-2-oxobutane-1,4-dioate (3) with sodium borohydride furnishes a 6:1 mixture of ethyl erythro-2-hydroxy-3-methylbutane-1,4-dioate (8) and ethyl threo-2-hydroxy-3-methylbutane-1,4-dioate (18).Hydrolysis of this mixture with aq. hydrochloric acid gives a mixture of acids from which pure erythro-2-hydroxy-3-methylbutane-1,4-dioic acid (4) has been isolated.The stereochemistry of 4 has been establishrd by PMR and by transforming it to the anhydride, erythro-dihydro-3-acetyloxy-4-methyl-2,5-furandione (26).
The Use of Microorganisms in Organic Synthesis. II. Microbiological Asymmetric Reduction of 2-Methyl-3-oxosuccinates
Akita, Hiroyuki,Furuichi, Akiya,Koshiji, Hiroko,Horikoshi, Koki,Oishi, Takeshi
, p. 4384 - 4390 (2007/10/02)
In order to synthesize four optically active methyl 2-methylmalates (10-13), microbiological asymmetric reduction of the corresponding dimethyl 2-methyl-3-oxosuccinate (9) was carried out.The β-keto diester 9 was found to be reduced by fermenting baker's yeast (Saccharomyces cerevisiae) and Candida albicans to afford a mixture of the (2R,3R)-isomer 10 and the (2S,3R)-isomer 11.Although the optical purity of 10 produced by Candida albicans was reasonably high (95percent e.e.), optical yields of other products were unexpectedly low.However, identification of the four possible isomers 14-17 was found to be easily carried out by means of nuclear magnetic resonance spectroscopy.Keywords - α-methyl-β-keto ester; methylmalate; asymmetric reduction; microbiological reduction; yeast; methyl 2-methylmalate
