Synfacts, Journal Year: 2023, Volume and Issue: 19(11), P. 1075 - 1075
Published: Oct. 14, 2023
Key words manganese catalysis - N-heterocycles metabolites gram-scale synthesis C–H oxidation
Language: Английский
Synfacts, Journal Year: 2023, Volume and Issue: 19(11), P. 1075 - 1075
Published: Oct. 14, 2023
Key words manganese catalysis - N-heterocycles metabolites gram-scale synthesis C–H oxidation
Language: Английский
Nature Chemistry, Journal Year: 2025, Volume and Issue: 17(3), P. 365 - 372
Published: Feb. 24, 2025
Language: Английский
Citations
3Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(33), P. 22982 - 22992
Published: Aug. 12, 2024
Incorporation of C(sp
Language: Английский
Citations
9Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(13), P. 8904 - 8914
Published: March 20, 2024
The C(sp3)–H bond oxygenation of a variety cyclopropane containing hydrocarbons with hydrogen peroxide catalyzed by manganese complexes aminopyridine tetradentate ligands was carried out. Oxidations were performed in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) and 2,2,2-trifluoroethanol (TFE) using different catalysts carboxylic acid co-ligands, where steric electronic properties systematically modified. Functionalization selectively occurs at the most activated C–H bonds that are α- to cyclopropane, providing access carboxylate or 2,2,2-trifluoroethanolate transfer products, no competition, favorable cases, from generally dominant hydroxylation reaction. formation mixtures unrearranged rearranged esters (oxidation HFIP presence acid) ethers TFE) full control over diastereoselectivity observed, confirming involvement delocalized cationic intermediates these transformations. Despite such complex mechanistic scenario, fine-tuning catalyst sterics electronics leveraging on relative contribution pathways reaction mechanism, product chemoselectivity could be achieved. Taken together, results reported herein provide powerful catalytic tools rationally manipulate ligand oxidations hydrocarbons, delivering novel products good yields and, some outstanding selectivities, expanding available toolbox for development synthetically useful functionalization procedures.
Language: Английский
Citations
7Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(29)
Published: July 10, 2023
An emerging trend in small-molecule pharmaceuticals, generally composed of nitrogen heterocycles (
Language: Английский
Citations
15Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(40), P. 22086 - 22096
Published: Sept. 26, 2023
A detailed study on the C(sp3)–H bond oxygenation reactions with H2O2 catalyzed by [Mn(OTf)2(TIPSmcp)] complex at methylenic sites of cycloalkyl and 1-alkyl substrates bearing 19 different electron-withdrawing functional groups (EW FGs) was carried out. Oxidations in MeCN were compared to corresponding ones strong hydrogen donating (HBD) solvents 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) nonafluoro tert-butyl alcohol (NFTBA). Formation products deriving from most remote observed, yields, product ratios (PR) for over next sites, associated site-selectivities that significantly increased going HFIP NFTBA. Unprecedented obtained oxidation cyclohexyl, cycloheptyl, cyclooctyl, 1-pentyl, 1-hexyl, 1-heptyl substrates, approaching >99%, 90%, 93%, 88% (PR >99, 9.4, 14, 7.5) cyclohexyl-2-pyridinecarboxylate, cycloheptyl-2-pyridinecarboxylate, cyclooctyl-4-nitrobenzenesulfonamide, 1-pentyl-3,5-dinitrobenzoate, 1-hexyl-3,5-dinitrobenzoate, 1-heptyl-3,5-dinitrobenzoate, respectively. The results are rationalized basis a polarity enhancement effect via synergistic electronic deactivation proximal imparted EWG coupled solvent HB. Compared previous procedures, provides opportunity tune site-selectivity among multiple methylenes substrate classes, extending determined native EWGs two carbon atoms. This uncovers simple procedure predictable, high-yielding, highly site-selective occurs under mild conditions, large scope, providing an extremely powerful tool be implemented synthetically useful procedures.
Language: Английский
Citations
14Synlett, Journal Year: 2024, Volume and Issue: 35(08), P. 862 - 876
Published: Jan. 15, 2024
Abstract The field of C–H functionalization chemistry has experienced rapid growth in the past twenty years, with increasingly powerful applications organic synthesis. Recognizing potential this emerging to impact drug discovery, a dedicated effort was established our laboratories more than ten years ago, goal facilitating application chemistries active medicinal-chemistry programs. Our approach centered around strategy late-stage (LSF) wherein is employed systematic and targeted manner generate high-value analogues from advanced leads. To successfully realize approach, we developed broadly useful LSF platforms workflows that increased success rates accelerated access new derivatives. strategy, when properly applied, enabled synthesis molecules designed address specific issues. Several case studies are presented, along descriptions group’s workflows. 1 Introduction 2 Building an Chemistry Toolbox 2.1 Borylation 2.2 Minisci Platforms 2.3 Automated Direct-Metalation Platform 3 Workflow 4 Application Case Studies 4.1 BTK Inhibitor Program 4.2 GPR40 Agonist 5 Conclusions
Language: Английский
Citations
5Analytical Methods, Journal Year: 2024, Volume and Issue: 16(7), P. 1093 - 1101
Published: Jan. 1, 2024
Recent strides in nanotechnology have given rise to nanozymes, nanomaterials designed emulate enzymatic functions. Despite their promise, challenges such as batch-to-batch variability and limited atomic utilization persist. This study introduces Pt(Glu)2, a platinum glutamic acid complex, versatile small-molecule peroxidase mimic. Synthesized through straightforward method, Pt(Glu)2 exhibits robust catalytic activity stability. Steady-state kinetics reveal lower Km value compared that of natural enzymes, signifying strong substrate affinity. was explored for controllable chemical modification integration into cascade reactions with surpassing other nanomaterials. Its facile synthesis seamless enhance beyond the capabilities nanozymes. In biosensing applications, enabled simultaneous detection cholesterol alkaline phosphatase human serum high selectivity sensitivity. These findings illustrate potential small molecule mimetics catalysis biosensing, paving way broader applications.
Language: Английский
Citations
4ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown
Published: June 2, 2025
Language: Английский
Citations
0Analytical Chemistry, Journal Year: 2024, Volume and Issue: unknown
Published: Dec. 3, 2024
Electrochemistry offers an effective means of mimicking enzymatic metabolic pathways, particularly the oxidative pathways catalyzed by cytochrome P450 superfamily. The electrochemical generation and identification metabolites are time-sensitive, necessitating adjustable cell designs for accurate mechanistic interpretation. We present a thin-layer electrode (TLE) that addresses needs both analytical synthetic drug metabolites. TLE's ability to conduct experiments on minute-to-hour time scale allows detailed observation reaction mechanisms not easily identified traditional methods. utility TLE was benchmarked oxidation acetaminophen, acebutolol, 2-acetyl-4-butyramidophenol, known produce quinone imine metabolites, i.e., NAPQI, upon oxidation. When combined with microelectrode (μE), enables probing concentration profiles these drugs. micromole pipette-type structure facilitate comprehensive structural elucidation intermediates products using chromatographic spectroscopic techniques.
Language: Английский
Citations
2Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(5), P. 103943 - 103943
Published: March 5, 2024
The drug discovery and development process encompasses the interrogation of metabolites arising from biotransformation drugs. Here we look at why, when how small-molecule drugs are synthesised perspective a specialist contract research organisation, with particular attention paid to projects for which regulatory oversight is relevant during this journey. To illustrate important aspects, recent case studies, trends learnings our experience making identifying over past ten years, along selected examples literature. Teaser: impact in clinical development, obligations, diverse challenging problems were solved real-life examples.
Language: Английский
Citations
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