10.1002/adsc.202100296
The research focuses on the semi-rational engineering of toluene dioxygenase (TDO) from Pseudomonas putida F1 to enhance its capability for the oxyfunctionalization of bicyclic aromatic compounds. The study involved generating single and double mutant libraries targeting 27 different positions at the active site and entrance channel of TDO. A total of 176 variants were created and tested with substrates such as naphthalene, 1,2,3,4-tetrahydroquinoline, and 2-phenylpyridine. Key mutations at positions M220, A223, and F366 significantly influenced product formation, chemo-, regio-, and enantioselectivity. The engineered TDO variants demonstrated the ability to convert bulkier substrates with unprecedented conversions, leading to the production of valuable chiral synthons like (+)-(R)-1,2,3,4-tetrahydroquinoline-4-ol and (+)-(1S,2R)-3-(pyridin-2-yl)cyclohexa-3,5-diene-1,2-diol with high yields and enantiomeric excess. The experiments utilized site-directed mutagenesis, biotransformations in recombinant E. coli strains, and analyses including HPLC-DAD, HPLC-ESI-MS, chiral HPLC-DAD, and NMR spectroscopy for product identification, quantification, and characterization.
10.1007/s11172-007-0159-0
The study focuses on the development of a new synthetic approach to epoxyisoindolo[2,1-a]quinolines, a class of compounds with potential pharmaceutical interest due to their antihypoxic properties and ability to inhibit human topoisomerase. The synthesis involves cycloaddition reactions of 2-furyl-substituted tetrahydroquinolines with maleic anhydride and acryloyl chloride. Key chemicals used in the study include furfurylideneanilines, alkenes, Lewis acids (such as ZnCl2, ZnI2, SnCl4, TiCl4, AlCl3, or Et2O?BF3), protic acids (like trifluoroacetic, oxalic, or p-toluenesulfonic acid), and activated alkenes. These chemicals serve various roles in the synthesis process, such as catalysts in the Povarov reaction, which is essential for the formation of 2-furyl-substituted tetrahydroquinolines, a precursor in the synthesis of the target epoxyisoindolo[2,1-a]quinolines. The study also explores the influence of the catalyst and solvent nature, as well as the electronic effects of substituents in the aryl moiety of furfurylideneanilines, on the efficiency of the cycloaddition reactions.
10.1016/j.bmcl.2010.01.071
The research aims to identify orally active cholesteryl ester transfer protein (CETP) inhibitors through the exploration of tetrahydrochinoline derivatives. The study builds on previous work with compounds like BAY 19-4789 and BAY 38-1315, which were discontinued due to toxicological and pharmacokinetic issues. The researchers synthesized and tested a series of new compounds, focusing on replacing the 4-fluorophenyl substituent with cycloalkyl groups to improve potency and pharmacokinetic properties. The most promising compound, 11b, demonstrated high potency in vitro and favorable pharmacokinetic properties in vivo, leading to its selection as a clinical candidate. The study concludes that the new compound 11b has the potential to improve the lipoprotein profile by increasing HDL cholesterol and lowering serum triglycerides, making it a viable candidate for further clinical development.
10.1002/1522-2675(20011017)84:10<2895::AID-HLCA2895>3.0.CO;2-0
The research investigates the selective hydrogenation of quinoline to 1,2,3,4-tetrahydroquinoline using rhodium catalysts modified with the tripodal polyphosphine ligand MeC(CH?PPh?)?. The study aims to elucidate the catalytic mechanism and identify the electronic requirements of the metal catalyst for efficient hydrogenation, which is crucial for the hydrodenitrogenation of N-heterocycles in raw oil materials. Key chemicals include quinoline (Q), the rhodium catalyst precursors [Rh(DMAD)(triphos)PF?] (1) and [Rh(S(C?H?)CH=CH?-C?H?S)(triphos)] (2), and various intermediates and products such as [Rh(H)(triphos)]?, [Rh(Q-κN)?(triphos-xP)]? (6a-c), and [Rh(H)(Q-xN)(triphos-xP)]PF? (7). The study employs high-pressure NMR spectroscopy, kinetic studies, and isotope labeling to understand the reaction pathways. The findings show that the hydrogenation rate has an inverse concentration dependence on quinoline and that the presence of a Bronsted acid like triflic acid significantly enhances the catalytic activity. The proposed mechanism involves the coordination of quinoline to the rhodium center, oxidative addition of hydrogen, and subsequent bond-breaking steps. The study concludes that the selective hydrogenation of quinoline can be effectively achieved with the [Rh(H)(triphos)]? fragment, and the results provide insights into designing improved catalysts for hydrodenitrogenation processes.
10.1002/chem.200800210
The study explores the use of gold catalysis to synthesize various heterocycles, including chromans, dihydrobenzofurans, dihydroindoles, and tetrahydroquinolines. The researchers prepared furans containing ynamide or alkynyl ether moieties in the side chain and used gold-catalyzed transformations to achieve these syntheses at room temperature through fast reactions. The heteroatom directly attached to the intermediate arene oxides stabilized the intermediates, leading to highly selective reactions, even with mono-substituted furans. The study involved various chemicals, including lithiated furans for the introduction of side chains, oxiranes and enones for synthesis of alcohols, and dichlorovinyl ethers and toluenesulfonamides as starting points for ynamide syntheses. The gold-catalyzed reactions resulted in the formation of the desired heterocycles with good yields and selectivity, highlighting the efficiency and versatility of gold catalysis in organic synthesis.
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