Résultat de la recherche
Synthesis and Reactions of 2-[1-Methyl-1-(pyrrolidin-2-yl)ethyl]-1H-pyrrole and Some Derivatives with Aldehydes: Chiral Structures Combining a Secondary-Amine Group with an 1H-Pyrrole Moiety as Excellent H-Bond Donor
The synthesis of compd. I (R = H) and its derivs. I (R = CF3, CO2Me) combining a pyrrolidine ring with an 1H-pyrrole unit is described. Their attempted usability as organocatalysts was not successful. Reacting these simple pyrrolidine derivs. with (E)-cinnamaldehyde led to tricyclic products. The final, major products were the pyrroloindolizidine tricycles, e.g. II, obtained via the iminium ion reacting intramolecularly with the nucleophilic ?-position of the 1H-pyrrole moiety. [on SciFinder(R)]
Artificial Transfer Hydrogenases Based on the Biotin−(Strept)avidin Technology:  Fine Tuning the Selectivity by Saturation Mutagenesis of the Host Protein
Incorporation of biotinylated racemic three-legged d6-piano stool complexes in streptavidin yields enantioselective transfer hydrogenation artificial metalloenzymes for the reduction of ketones. Having identified the most promising organometallic catalyst precursors in the presence of wild-type streptavidin, fine-tuning of the selectivity is achieved by saturation mutagenesis at position S112. This choice for the genetic optimization site is suggested by docking studies which reveal that this position lies closest to the biotinylated metal upon incorporation into streptavidin. For aromatic ketones, the reaction proceeds smoothly to afford the corresponding enantioenriched alcohols in up to 97% ee (R) or 70% (S). On the basis of these results, we suggest that the enantioselection is mostly dictated by CH/π interactions between the substrate and the η6-bound arene. However, these enantiodiscriminating interactions can be outweighed in the presence of cationic residues at position S112 to afford the opposite enantiomers of the product.
Catalytic Epoxidation of Alkenes by the Manganese Complex of a Reduced Porphyrinogen Macrocycle
The present paper details the first application of a fully reduced meso-octamethylporphyrinogen macrocycle as an effective ligand for simple operative manganese-catalyzed alkene epoxidn. The efficiency of the novel catalyst was detd. in the presence of various oxidants, apical ligands and acidic/basic additives. Higher reactivity was found in favor of electron-rich alkenes, whereas an electron-deficient conjugated alkene appeared to be a poor substrate in the screening. Sulfur additives were active as apical ligands, whereas nitrogen-contg. additives influenced the reactivity only moderately. Cis-Stilbene and 3?-acetoxy-5-cholestene were epoxidized in a stereoselective manner. The x-ray structures of the new manganese complexes were detd. and showed a rigid planar coordination geometry of the satd. macrocyclic ligand to the metal center. [on SciFinder(R)]
Chemogenetic protein engineering: optimization of artificial metalloenzymes for oxidation and reduction reactions
La capacité d’optimiser ou de créer de nouveaux catalyseurs pour des transformations énantioselectives a un impact majeur dans les applications de la chimie actuelle. Les métalloenzymes artificielles se situent à l’interface entre la catalyse organométallique et celle enzymatique et ont un immense potentiel d’optimisation, qui combine des méthodes chimiques et génétiques pour créer la diversité. En termes d’activité, répertoire de réactions et de substrats ou conditions opératoires, elles exploitent la versatilité de la chimie organométallique. Par contre, l’énantiosélectivité est déterminée par la protéine, qui assure une seconde sphère de coordination très bien définie, réminiscente des biocatalyseurs. L’incorporation des complexes biotinylés catalytiquement actifs dans la streptavidine permet la création des métalloenzymes artificielles pour le transfert hydrogénant des cètones prochirales. Les tendances générales de l’activité et de la sélectivité des catalyseurs sont assurées par le choix de la partie organométallique suite à un premier criblage. L’étude de la structure d’une telle enzyme artificielle est à la base d’une « évolution rationnelle », dans laquelle des étapes successives de mutagenèse de saturation à des positions attentivement choisies sont combinées avec un criblage de l’énantiosélectivité. Cette méthode permet l’identification des catalyseurs hautement sélectifs pour la réduction de substrats difficiles, comme par exemple les dialkyl cètones. Le réseau des liaisons hydrogène dans le site actif de la streptavidine est très bien défini et permet également l’insertion de composés non-biotinylés, tels des ions métalliques catalytiquement actifs. L’environnement asymétrique assuré par la protéine peut être exploité dans des réactions de sulfoxydation énantiosélective catalysée par du vanadium. Ces réactions montrent que l’incorporation spécifique d’un métal peut transformer une protéine sans activité enzymatique en un biocatalyseur utilisé en synthèse organique., The ability to optimize or to find new catalysts for enantioselective transformations has a major impact in today’s chemistry. Artificial metalloenzymes lie at the interface between organometallic and enzymatic catalysis and have an immense optimization potential, which combines chemical and genetic methods to screen diversity space. In terms of activity, reaction repertoire, substrate range and operating conditions, they take advantage of the versatility of the organometallic chemistry. In contrast, the enantioselectivity is determined by the biomolecular scaffold, which provides a well defined second coordination sphere to the organometallic moiety, reminiscent of enzymes. Incorporation of catalytically active biotinylated complexes within streptavidin affords artificial metalloenzymes for the transfer hydrogenation of prochiral ketones. The activity and selectivity trends of the catalysts are ensured by the choice of the chemical fragment in a first screening round. Insight into the structure of an artificial enzyme forms the basis of a designed evolution step, which relies on successive rounds of saturation mutagenesis at carefully selected positions and screening for enantioselectivity. This procedure allows the identification of highly selective scaffolds for the reduction of challenging substrates, such as dialkyl ketones. The well-tailored hydrogen bond network of streptavidin’s binding cavity can also accommodate non-biotinylated frameworks, such as catalytically active metal ions. The enantiodiscriminating environment provided by the host protein can be exploited to perform highly enantioselective vanadium-catalyzed oxidations of several prochiral sulfides, demonstrating that specific metal binding can transform a non-enzymatic protein into an enantioselective biocatalyst with synthetic utility.