3884-92-2Relevant academic research and scientific papers
Nitrated Fatty Acids Modulate the Physical Properties of Model Membranes and the Structure of Transmembrane Proteins
Franz, Johannes,Bereau, Tristan,Pannwitt, Stefanie,Anbazhagan, Veerappan,Lehr, Alexander,Nubbemeyer, Udo,Dietz, Ulrich,Bonn, Mischa,Weidner, Tobias,Schneider, Dirk
, p. 9690 - 9697 (2017)
Nitrated fatty acids (NO2-FAs) act as anti-inflammatory signal mediators, albeit the molecular mechanisms behind NO2-FAs’ influence on diverse metabolic and signaling pathways in inflamed tissues are essentially elusive. Here, we combine fluorescence measurements with surface-specific sum frequency generation vibrational spectroscopy and coarse-grained computer simulations to demonstrate that NO2-FAs alter lipid organization by accumulation at the membrane–water interface. As the function of membrane proteins strongly depends on both, protein structure as well as membrane properties, we consecutively follow the structural dynamics of an integral membrane protein in presence of NO2-FAs. Based on our results, we suggest a molecular mechanism of the NO2-FA in vivo activity: Driven by the NO2-FA-induced lipid layer reorganization, the structure and function of membrane-associated (signaling) proteins is indirectly affected.
Synthesis of 1-Palmitoyl-2-((E)-9- and (E)-10-nitrooleoyl)- sn -glycero-3-phosphatidylcholines
Dietz, Ulrich,Frank, Andrea,Lehr, Alexander,Münch, Winfried,Nubbemeyer, Udo
supporting information, p. 3295 - 3304 (2019/08/28)
Extensive investigation of nitrated phospholipids in connection with various biologically important processes requires reliable access to suitable material. A selective chemical synthesis introducing a defined nitrofatty acid at the sn -2 position of a 2-lyso sn -glycero-3-phosphatidylcholine was developed. Given that the nitroalkene moiety of both reactant nitrofatty acid derivative and the product esters is characterised by particular sensitivity to nucleophile addition and, depending on the intermediate, subsequent olefin isomerisation and retro-Henry-type reaction, a reliable two-step ester formation was introduced. The activation of the nitrofatty acid succeeded after reaction with trichlorobenzoyl chloride, and the mixed anhydride could be isolated via extractive work-up. Subsequent reaction with 1-palmitoyl-2-lyso- sn -glycero-3-phosphatidylcholine enabled the sn -2 esterification to be achieved with high yield by using a minimum of reagents, avoiding the formation of side products and facilitating final isolation and purification.
Nickel-Catalyzed Selective Reduction of Carboxylic Acids to Aldehydes
Iosub, Andrei V.,Morav?ík, ?tefan,Wallentin, Carl-Johan,Bergman, Joakim
supporting information, p. 7804 - 7808 (2019/10/14)
The direct reduction of carboxylic acids to aldehydes is a fundamental transformation in organic synthesis. The combination of an air-stable Ni precatalyst, dimethyl dicarbonate as an activator, and silane reductant effects this reduction for a wide variety of substrates, including pharmaceutically relevant structures, in good yields and with no overreduction to alcohols. Moreover, this methodology is scalable, allows access to deuterated aldehydes, and is also compatible with one-pot utilization of the aldehyde products.
Asymmetric α-oxyamination of aldehydes by synergistic catalysis of imidazolethiones and metal salts
Liang, Xianrui,Li, Na,Chen, Xinlei,Su, Weike
, p. 44039 - 44042 (2014/12/11)
Novel and efficient imidazolethione catalysts combined with metal salts were successfully introduced to the asymmetric α-oxyamination of aldehydes. The desired products with high yields and good to excellent enantioselectivities were obtained via a one-pot oxidation-oxyamination reaction system.
Precise supramolecular control of selectivity in the Rh-catalyzed hydroformylation of terminal and internal alkenes
Dydio, Pawel,Detz, Remko J.,Reek, Joost N. H.
supporting information, p. 10817 - 10828 (2013/08/23)
In this study, we report a series of DIMPhos ligands L1-L3, bidentate phosphorus ligands equipped with an integral anion binding site (the DIM pocket). Coordination studies show that these ligands bind to a rhodium center in a bidentate fashion. Experiments under hydroformylation conditions confirm the formation of the mononuclear hydridobiscarbonyl rhodium complexes that are generally assumed to be active in hydroformylation. The metal complexes formed still strongly bind the anionic species in the binding site of the ligand, without affecting the metal coordination sphere. These bifunctional properties of DIMPhos are further demonstrated by the crystal structure of the rhodium complex with acetate anion bound in the binding site of the ligand. The catalytic studies demonstrate that substrate preorganization by binding in the DIM pocket of the ligand results in unprecedented selectivities in hydroformylation of terminal and internal alkenes functionalized with an anionic group. Remarkably, the selectivity controlling anionic group can be even 10 bonds away from the reactive double bond, demonstrating the potential of this supramolecular approach. Control experiments confirm the crucial role of the anion binding for the selectivity. DFT studies on the decisive intermediates reveal that the anion binding in the DIM pocket restricts the rotational freedom of the reactive double bound. As a consequence, the pathway to the undesired product is strongly hindered, whereas that for the desired product is lowered in energy. Detailed kinetic studies, together with the in situ spectroscopic measurements and isotope-labeling studies, support this mode of operation and reveal that these supramolecular systems follow enzymatic-type Michaelis-Menten kinetics, with competitive product inhibition.
Mitochondria-Targeted Inhibitors of Cytochrome C Peroxidase for Protection from Apoptosis
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Paragraph 0260-0262, (2013/08/15)
The present application is directed to novel imidazole-substituted fatty acids that have been functionalized with an alkyl triphenylphosphonium group, compositions comprising these compounds and their use as inhibitors of cytochrome c peroxidase, in particular for the treatment and prevention of apoptosis.
Remote supramolecular control of catalyst selectivity in the hydroformylation of alkenes
Dydio, Pawea,Dzik, Wojciech I.,Lutz, Martin,De-Bruin, Bas,Reek, Joost N. H.
supporting information; experimental part, p. 396 - 400 (2011/03/16)
In the pocket: The supramolecular interactions between a Rh phosphine catalyst equipped with an anion-binding pocket and alkenes that contain anionic functionalities (see picture) provide an excellent design concept to achieve remote control of the regioselectivity in hydroformylation reactions. The 4-pentenoate and 3-butenylphosphonate, which fit tightly between the Rh center and the pocket, were hydroformylated with unprecedented selectivity.
Kinetic analysis of terminal and unactivated C-H bond oxyfunctionalization in fatty acid methyl esters by monooxygenase-based whole-cell biocatalysis
Schrewe, Manfred,Magnusson, Anders O.,Willrodt, Christian,Buehler, Bruno,Schmid, Andreas
experimental part, p. 3485 - 3495 (2012/03/26)
The alkane monooxygenase AlkBGT from Pseudomonas putida GPo1 constitutes a versatile enzyme system for the ω-oxyfunctionalization of medium chain-length alkanes. In this study, recombinant Escherichia coli W3110 expressing alkBGT was investigated as whole-cell catalyst for the regioselective biooxidation of fatty acid methyl esters to terminal alcohols. The ω-functionalized products are of general economic interest, serving as building blocks for polymer synthesis. The whole-cell catalysts proved to functionalize fatty acid methyl esters with a medium length alkyl chain specifically at the ω-position. The highest specific hydroxylation activity of 104 U gCDW-1 was obtained with nonanoic acid methyl ester as substrate using resting cells of E. coli W3110 (pBT10). In an optimized set-up, maximal 9-hydroxynonanoic acid methyl ester yields of 95% were achieved. For this specific substrate, apparent whole-cell kinetic parameters were determined with a Vmax of 204±9 U gCDW -1, a substrate uptake constant (KS) of 142±17 μM, and a specificity constant Vmax/KS of 1.4 U g CDW-1 μM-1 for the formation of the terminal alcohol. The same E. coli strain carrying additional alk genes showed a different substrate selectivity. A comparison of biocatalysis with whole cells and enriched enzyme preparations showed that both substrate availability and enzyme specificity control the efficiency of the whole-cell bioconversion of the longer and more hydrophobic substrate dodecanoic acid methyl ester. The efficient coupling of redox cofactor oxidation and product formation, as determined in vitro, combined with the high in vivo activities make E. coli W3110 (pBT10) a promising biocatalyst for the preparative synthesis of terminally functionalized fatty acid methyl esters. Copyright
Regio- and stereospecific syntheses and nitric oxide donor properties of (E)-9- and (E)-10-nitrooctadec-9-enoic acids
Gorczynski, Michael J.,Huang, Jinming,King, S. Bruce
, p. 2305 - 2308 (2007/10/03)
Nitrated fatty acids act as endogenous peroxisome proliferator-activated receptor γ (PPARγ) ligands and nitric oxide (NO) donors. We describe the first specific preparation of the two regioisomers of nitrooleic acid, (E)-9-nitrooctadec-9-enoic acid (1) an
Highly selective intra- and intermolecular coupling reactions of diazo compounds to form cis-alkenes using a ruthenium porphyrin catalyst
Li, Gong-Yong,Che, Chi-Ming
, p. 1621 - 1623 (2007/10/03)
[Ru(2,6-Cl2TPP)(CO)] catalyzed intramolecular coupling reactions of bisdiazoacetates and intermolecular coupling reactions of monodiazoacetates to afford the coupling products in up to 76% and 93% yields, respectively. Only the cis isomers were obtained from the reactions. Employing such a ruthenium-catalyzed coupling reaction of a diazo compound as a key step allowed the synthesis of Patulolide B in 67% yield with a ratio of >40:1 against its trans isomer.
