73323-68-9Relevant articles and documents
Highly Regio- and Enantioselective Hydroformylation of Vinyl Esters Using Bidentate Phosphine,P-Chiral Phosphorodiamidite Ligands
Schmitz, Christian,Holthusen, Katharina,Leitner, Walter,Franciò, Giancarlo
, p. 1584 - 1589 (2016/03/15)
Hybrid bidentate phosphine-phosphorodiamidite ligands based on a chiral Betti base backbone and diphenylphosphinoaniline derivatives have been prepared (BettiPhos). The ligands possess a stereogenic P atom at the phosphorodiamidite moiety, whose configuration can be largely controlled by the synthetic route and the choice of base and solvent. The new ligands were applied in the rhodium-catalyzed asymmetric hydroformylation (AHF) of vinyl esters and vinyl amides. Very high enantioselectivities of up to 97% ee accompanied by excellent regioselectivities (up to b/l > 1000) were obtained using the BettiPhos ligand (SC,SC,RP,SC)-4b bearing an additional chiral group at the aniline nitrogen. The catalyst resting state [RhH(CO)2{(SC,SC,RP,SC)-4b}] was investigated by high pressure-NMR studies, revealing an equatorial-apical coordination of the bidentate ligand where the two phosphorus donors rapidly exchange their positions through an intermediate with the ligand bound via the phosphine group only.
Mechanistic and structural analyses of the roles of active site residues in yeast polyamine oxidase Fms1: Characterization of the N195A and D94N enzymes
Adachi, Mariya S.,Taylor, Alexander B.,Hart, P. John,Fitzpatrick, Paul F.
, p. 8690 - 8697 (2013/01/15)
Flavoprotein Fms1 from Saccharomyces cerevisiae catalyzes the oxidation of spermine in the biosynthetic pathway for pantothenic acid. The same reaction is catalyzed by the mammalian polyamine and spermine oxidases. The active site of Fms1 contains three amino acid residues positioned to interact with the polyamine substrate, His67, Asn195, and Asp94. These three residues form a hydrogen-bonding triad with Asn195 being the central residue. Previous studies of the effects of mutating His67 are consistent with that residue being important both for interacting with the substrate and for maintaining the hydrogen bonds in the triad [Adachi, M. S., Taylor, A. B., Hart, P. J., and Fitzpatrick, P. F. (2012) Biochemistry 51, 4888-4897]. The N195A and D94N enzymes have now been characterized to evaluate their roles in catalysis. Both mutations primarily affect the reductive half-reaction. With N 1-acetylspermine as the substrate, the rate constant for flavin reduction decreases ～450-fold for both mutations; the effects with spermine as the substrate are smaller, 20-40-fold. The kcat/Kamine- and kcat-pH profiles with N1-acetylspermine are only slightly changed from the profiles for the wild-type enzyme, consistent with the pKa values arising from the amine substrate or product and not from active site residues. The structure of the N195A enzyme was determined at a resolution of 2.0 ?. The structure shows a molecule of tetraethylene glycol in the active site and establishes that the mutation has no effect on the protein structure. Overall, the results are consistent with the role of Asn195 and Asp94 being to properly position the polyamine substrate for oxidation.
A lysine conserved in the monoamine oxidase family is involved in oxidation of the reduced flavin in mouse polyamine oxidase
Henderson Pozzi, Michelle,Fitzpatrick, Paul F.
experimental part, p. 83 - 88 (2011/10/09)
Lysine 315 of mouse polyamine amine oxidase corresponds to a lysine residue that is conserved in the flavoprotein amine oxidases of the monoamine oxidase structural family. In several structures, this lysine residue forms a hydrogen bond to a water molecule that is hydrogen-bonded to the flavin N(5). Mutation of Lys315 in polyamine oxidase to methionine was previously shown to have no effect on the kinetics of the reductive half-reaction of the enzyme (M. Henderson Pozzi, V. Gawandi, P.F. Fitzpatrick, Biochemistry 48 (2009) 1508-1516). In contrast, the mutation does affect steps in the oxidative half-reaction. The kcat value is unaffected by the mutation; this kinetic parameter likely reflects product release. At pH 10, the kcat/Km value for oxygen is 25-fold lower in the mutant enzyme. The kcat/KO2 value is pH-dependent for the wild-type enzyme, decreasing below a pKa of 7.0, while this kinetic parameter for the mutant enzyme is pH-independent. This is consistent with the neutral form of Lys315 being required for more rapid flavin oxidation. The solvent isotope effect on the kcat/KO2 value increases from 1.4 in the wild-type enzyme to 1.9 in the mutant protein, and the solvent inventory changes from linear to bowed. The effects of the mutation can be explained by the lysine orienting the bridging water so that it can accept the proton from the flavin N(5) during flavin oxidation. In the mutant enzyme the lysine amine would be replaced by a water chain.
Identification of a new endogenous metabolite and the characterization of its protein interactions through an immobilization approach
Kalisiak, Jarostaw,Trauger, Sunia A.,Kalisiak, Ewa,Morita, Hirotoshi,Fokin, Valery V.,et al.
experimental part, p. 378 - 386 (2009/06/28)
The emerging field of global mass-based metabolomics provides a platformfor discovering unknown metabolites and their specific biochemical path ways. We report the identification of a new endogenous metabolite, N4-(N- acetylaminopropyl)spermidine and the use of a novel proteomics based method for the investigation of its protein interaction using metabolite immobilization on agarose beads. The metabolite was isolated from the organism Pyrococcus furiosus, and structurally characterized through an iterative process of synthesizing candidate molecules and comparative analysis using accurate mass LC-MS/MS. An approach developed for the selective preparation of N 1-acetylthermospermine, one ofthe possible structures of the unknown metabolite, provides a convenien t route to new polyamine derivatives through methylation on the N8 and N4 of the thermospermine scaffold. The biochemical role of the novel metabolite as well as that of two other polyamines: spermidine and agmatine is investigated through metabolite immobilization and incubation with native proteins. The identification of eleven proteins that uniquely bind with N4-(N-acetylaminopropyl)spermidine, provides information on the role of this novel metabolite in the native organism. Identified proteins included hypothetical ones such as PF0607 and PF1199, and those involved in translation, DNA synthesis and the urea cycle like translation initiation factor IF-2, 50S ribosomal proteinL14e, DNA-directed RNA polymerase, and ornithine carbamoyltransferase. The immobilization approach demonstrated here has the potential for appl ication to other newly discovered endogenous metabolites found through untargeted metabolomics, as a preliminary screen for generating a list ofproteins that could be further investigated for specific activity.
Asymmetric Hydroformylation and Hydrocarboxylation of Enamides. Synthesis of Alanine and Proline
Becker, Y.,Eisenstadt, A.,Stille, J. K.
, p. 2145 - 2151 (2007/10/02)
Carbonyltris(triphenylphosphine)hydridorhodium (1) catalyzed the hydroformylation of N-vinylimides in the presence of optically active 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane (DIOP) or 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(5H-dibenzophospholyl)butane (DIPHOL) to afford optically active α-amido aldehydes.Linear disubstituted N-vinylimides or -amides reacted very sluggishly, while the cyclic N-acyl-2-pyrroline (19) was very reactive.In the unsubstituted N-vinylimides moderate (20-40percent ee) asymmetric induction was observed.The optically active α-amido aldehydes were readily converted to the corresponding α-amino acids.Asymmetric hydrocarboxylation of the same substrates in the presence of bis(triphenylphosphine)palladium chloride (2) produced α-amido esters in low optical purity.
