Accessing Drug Metabolites via Transition-Metal Catalyzed C−H Oxidation: The Liver as Synthetic Inspiration

The medicinal chemist's toolbox for late stage functionalization of drug-like molecules

(2016) Tim Cernak et al.   CHEMICAL SOCIETY REVIEWS

Biotransformation and bioactivation reactions – 2015 literature highlights

(2016) Thomas A. Baillie et al.   DRUG METABOLISM REVIEWS

Definitive Metabolite Identification Coupled with Automated Ligand Identification System (ALIS) Technology: A Novel Approach to Uncover Structure–Activity Relationships and Guide Drug Design in a Factor IXa Inhibitor Program

(2016) Ting Zhang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Mechanism of the CuII-catalyzed benzylic oxygenation of (aryl)(heteroaryl)methanes with oxygen

(2016) Hans Sterckx et al.   Chemical Science

Manganese Catalyzed C–H Halogenation

(2015) Wei Liu et al.   ACCOUNTS OF CHEMICAL RESEARCH

Directortho-Hydroxylation of 2-Phenylpyridines using Palladium(II) Chloride and Hydrogen Peroxide

(2015) Tomoaki Yamaguchi et al.   ADVANCED SYNTHESIS & CATALYSIS

Iron-Catalyzed CαH Oxidation of Tertiary, Aliphatic Amines to Amides under Mild Conditions

(2015) Christopher J. Legacy et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Directed evolution of cytochrome P450 enzymes for biocatalysis: exploiting the catalytic versatility of enzymes with relaxed substrate specificity

(2015) James B.Y.H. Behrendorff et al.   BIOCHEMICAL JOURNAL

One-pot synthesis of human metabolites of SAR548304 by fungal peroxygenases

(2015) Jan Kiebist et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Drug Oxidation by Cytochrome P450BM3: Metabolite Synthesis and Discovering New P450 Reaction Types

(2015) Xinkun Ren et al.   CHEMISTRY-A EUROPEAN JOURNAL

Cu(II)-Mediated C(sp2)–H Hydroxylation

(2015) Shang-Zheng Sun et al.   JOURNAL OF ORGANIC CHEMISTRY

Iridium-Catalyzed Borylation of Primary Benzylic C–H Bonds without a Directing Group: Scope, Mechanism, and Origins of Selectivity

(2015) Matthew A. Larsen et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Iridium-Catalyzed Silylation of Aryl C–H Bonds

(2015) Chen Cheng et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Mechanism of the Palladium-Catalyzed Arene C–H Acetoxylation: A Comparison of Catalysts and Ligand Effects

(2015) Amanda K. Cook et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Platinum-Catalyzed, Terminal-Selective C(sp3)–H Oxidation of Aliphatic Amines

(2015) Melissa Lee et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Remote Oxidation of Aliphatic C–H Bonds in Nitrogen-Containing Molecules

(2015) Jennifer M. Howell et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Silylation of C–H bonds in aromatic heterocycles by an Earth-abundant metal catalyst

(2015) Anton A. Toutov et al.   NATURE

Comparative Study of the Limitations and Challenges in Atom-Transfer C–H Oxidations

(2015) Ashley M. Adams et al.   ORGANIC LETTERS

Access to drug metabolites via C–H functionalization: copper-catalyzed aerobic oxidation of N , N -dimethylalkylamines in complex pharmaceuticals

(2015) Julien Genovino et al.   TETRAHEDRON LETTERS

Surface-modified electrodes in the mimicry of oxidative drug metabolism

(2015) Tao Yuan et al.   TRAC-TRENDS IN ANALYTICAL CHEMISTRY

Electrosynthesis methods and approaches for the preparative production of metabolites from parent drugs

(2015) Turan Gul et al.   TRAC-TRENDS IN ANALYTICAL CHEMISTRY

Electrochemical generation of drug metabolites with applications in drug discovery and development

(2015) Ulrik Jurva et al.   TRAC-TRENDS IN ANALYTICAL CHEMISTRY

Improving Physical Properties via CH Oxidation: Chemical and Enzymatic Approaches

(2014) Quentin Michaudel et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Silver-Catalyzed Oxidative Activation of Benzylic CH Bonds for the Synthesis of Difluoromethylated Arenes

(2014) Peng Xu et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Room-Temperatureortho-Alkoxylation and -Halogenation ofN-Tosylbenzamides by Using Palladium(II)-Catalyzed CH Activation

(2014) Florent Péron et al.   CHEMISTRY-A EUROPEAN JOURNAL

A Simple Litmus Test for Aldehyde Oxidase Metabolism of Heteroarenes

(2014) Fionn O’Hara et al.   JOURNAL OF MEDICINAL CHEMISTRY

Iridium-Catalyzed Regioselective Silylation of Secondary Alkyl C–H Bonds for the Synthesis of 1,3-Diols

(2014) Bijie Li et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Iridium-Catalyzed C–H Borylation of Heteroarenes: Scope, Regioselectivity, Application to Late-Stage Functionalization, and Mechanism

(2014) Matthew A. Larsen et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Oxidant-Free Conversion of Cyclic Amines to Lactams and H2 Using Water As the Oxygen Atom Source

(2014) Julia R. Khusnutdinova et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Late Stage Benzylic C–H Fluorination with [18F]Fluoride for PET Imaging

(2014) Xiongyi Huang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Status of Reactive Non-Heme Metal–Oxygen Intermediates in Chemical and Enzymatic Reactions

(2014) Kallol Ray et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Rhodium-Catalyzed Intermolecular C-H Silylation of Arenes with High Steric Regiocontrol

(2014) C. Cheng et al.   SCIENCE

Dehydroabietylamine derivatives as multifunctional agents for the treatment of Alzheimer's disease

(2014) Yingying Cao et al.   MedChemComm

Generation of statin drug metabolites through electrochemical and enzymatic oxidations

(2013) Smriti Khera et al.   ANALYTICAL AND BIOANALYTICAL CHEMISTRY

Manganese-Catalyzed Oxidative Benzylic C-H Fluorination by Fluoride Ions

(2013) Wei Liu et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Cover Picture: Recoding the Genetic Code with Selenocysteine (Angew. Chem. Int. Ed. 1/2014)

(2013) Markus J. Bröcker et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Emerging technologies for metabolite generation and structural diversification

(2013) Kevin P. Cusack et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Sustainable Practices in Medicinal Chemistry: Current State and Future Directions

(2013) Marian C. Bryan et al.   JOURNAL OF MEDICINAL CHEMISTRY

Complementation of Biotransformations with Chemical C–H Oxidation: Copper-Catalyzed Oxidation of Tertiary Amines in Complex Pharmaceuticals

(2013) Julien Genovino et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Cu-Catalyzed Mild C(sp2)–H Functionalization Assisted by Carboxylic Acids en Route to Hydroxylated Arenes

(2013) Joan Gallardo-Donaire et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Catalyst-Controlled Aliphatic C–H Oxidations with a Predictive Model for Site-Selectivity

(2013) Paul E. Gormisky et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Metal-free oxidation of aromatic carbon–hydrogen bonds through a reverse-rebound mechanism

(2013) Changxia Yuan et al.   NATURE

Oxidative aliphatic C-H fluorination with manganese catalysts and fluoride ion

(2013) Wei Liu et al.   Nature Protocols

A convenient chemical-microbial method for developing fluorinated pharmaceuticals

(2013) Tara V. Bright et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Preparative Microfluidic Electrosynthesis of Drug Metabolites

(2013) Romain Stalder et al.   ACS Medicinal Chemistry Letters

Pd-Catalyzed CH Oxygenation with TFA/TFAA: Expedient Access to Oxygen-Containing Heterocycles and Late-Stage Drug Modification

(2012) Gang Shan et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Synthesis of Aryl(di)azinyl Ketones through Copper- and Iron-catalyzed Oxidation of the Methylene Group of Aryl(di)azinylmethanes

(2012) Johan De Houwer et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Cytochrome P450 (CYP) enzymes and the development of CYP biosensors

(2012) Elizabeth Schneider et al.   BIOSENSORS & BIOELECTRONICS

Aerobic oxidative N-dealkylation of tertiary amines in aqueous solution catalyzed by rhodium porphyrins

(2012) Zhen Ling et al.   CHEMICAL COMMUNICATIONS

Use of Small-Molecule Crystal Structures To Address Solubility in a Novel Series of G Protein Coupled Receptor 119 Agonists: Optimization of a Lead and in Vivo Evaluation

(2012) James S. Scott et al.   JOURNAL OF MEDICINAL CHEMISTRY

Directed Metal (Oxo) Aliphatic C–H Hydroxylations: Overriding Substrate Bias

(2012) Marinus A. Bigi et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Controlled Oxidation of Remote sp3 C–H Bonds in Artemisinin via P450 Catalysts with Fine-Tuned Regio- and Stereoselectivity

(2012) Kaidong Zhang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Opioid Metabolism

(2012) Howard S. Smith   MAYO CLINIC PROCEEDINGS

Catalytic functionalization of unactivated primary C–H bonds directed by an alcohol

(2012) Eric M. Simmons et al.   NATURE

Iridium-Catalyzed, Substrate-Directed C–H Borylation Reactions of Benzylic Amines

(2012) Andrew J. Roering et al.   ORGANIC LETTERS

Direct and Selective Benzylic Oxidation of Alkylarenes via C–H Abstraction Using Alkali Metal Bromides

(2012) Katsuhiko Moriyama et al.   ORGANIC LETTERS

Oxidative Aliphatic C-H Fluorination with Fluoride Ion Catalyzed by a Manganese Porphyrin

(2012) W. Liu et al.   SCIENCE

Adding Aliphatic C-H Bond Oxidations to Synthesis

(2012) M. C. White   SCIENCE

Simple and Facile Benzylic C-H Oxidation Using (Diacetoxyiodo)benzene and Catalytic Sodium Azide

(2012) Vikas N. Telvekar et al.   SYNTHETIC COMMUNICATIONS

Catalytic C–H oxidation by a triazamacrocyclic ruthenium complex

(2012) Eric McNeill et al.   Chemical Science

Escape from Flatland 2: complexity and promiscuity

(2012) Frank Lovering   MedChemComm

Metabolism-guided drug design

(2012) Antonia F. Stepan et al.   MedChemComm

Tuning P450 Enzymes as Oxidation Catalysts

(2012) Rudi Fasan   ACS Catalysis

Developments in the Aerobic Oxidation of Amines

(2012) Martin T. Schümperli et al.   ACS Catalysis

LC–MS-based metabolomics in profiling of drug metabolism and bioactivation

(2012) Feng Li et al.   Acta Pharmaceutica Sinica B

Electrochemical Oxidation by Square-Wave Potential Pulses in the Imitation of Oxidative Drug Metabolism

(2011) Eslam Nouri-Nigjeh et al.   ANALYTICAL CHEMISTRY

Remarkably High Reactivity of Pd(OAc)2/Pyridine Catalysts: Nondirected CH Oxygenation of Arenes

(2011) Marion H. Emmert et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

If CH Bonds Could Talk: Selective CH Bond Oxidation

(2011) Timothy Newhouse et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Preparation of human drug metabolites using fungal peroxygenases

(2011) Marzena Poraj-Kobielska et al.   BIOCHEMICAL PHARMACOLOGY

Lead diversification. Application to existing drug molecules: Mifepristone 1 and antalarmin 8

(2011) M. Abid Masood et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Lead Diversification 2: Application to P38, gMTP and lead compounds

(2011) M. Abid Masood et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Structural Alert/Reactive Metabolite Concept as Applied in Medicinal Chemistry to Mitigate the Risk of Idiosyncratic Drug Toxicity: A Perspective Based on the Critical Examination of Trends in the Top 200 Drugs Marketed in the United States

(2011) Antonia F. Stepan et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Synthesis of Catechols from Phenols via Pd-Catalyzed Silanol-Directed C–H Oxygenation

(2011) Chunhui Huang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Catalysis for fluorination and trifluoromethylation

(2011) Takeru Furuya et al.   NATURE

Diverting non-haem iron catalysed aliphatic C–H hydroxylations towards desaturations

(2011) Marinus A. Bigi et al.   Nature Chemistry

Development of biomimetic catalytic oxidation methods and non-salt methods using transition metal-based acid and base ambiphilic catalysts

(2011) Shun-Ichi MURAHASHI   PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES

Lidocaine Oxidation by Electrogenerated Reactive Oxygen Species in the Light of Oxidative Drug Metabolism

(2010) Eslam Nouri-Nigjeh et al.   ANALYTICAL CHEMISTRY

Recombinant human cytochrome P450 monooxygenases for drug metabolite synthesis

(2010) Kirsten Schroer et al.   BIOTECHNOLOGY AND BIOENGINEERING

Combinatorial Alanine Substitution Enables Rapid Optimization of Cytochrome P450BM3 for Selective Hydroxylation of Large Substrates

(2010) Jared C. Lewis et al.   CHEMBIOCHEM

Identification of Quinone Imine Containing Glutathione Conjugates of Diclofenac in Rat Bile

(2010) Daniel J. Waldon et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Enzymatic functionalization of carbon–hydrogen bonds

(2010) Jared C. Lewis et al.   CHEMICAL SOCIETY REVIEWS

Transition-Metal-Catalyzed Synthesis of Hydroxylated Arenes

(2010) Diego A. Alonso et al.   CHEMISTRY-A EUROPEAN JOURNAL

Validation of Isolated Metabolites from Drug Metabolism Studies as Analytical Standards by Quantitative NMR

(2010) G. S. Walker et al.   DRUG METABOLISM AND DISPOSITION

Ruthenium-Catalyzed Hydroxylation of Unactivated Tertiary C−H Bonds

(2010) Eric McNeill et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Iridium-Catalyzed AreneOrtho-Silylation by Formal Hydroxyl-Directed C−H Activation

(2010) Eric M. Simmons et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Manganese Porphyrins Catalyze Selective C−H Bond Halogenations

(2010) Wei Liu et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Combined Effects on Selectivity in Fe-Catalyzed Methylene Oxidation

(2010) M. S. Chen et al.   SCIENCE

Synthesis of potential drug metabolites by a modified Udenfriend reaction

(2010) Roger Slavik et al.   TETRAHEDRON LETTERS

Reactive Intermediates in Oxygenation Reactions with Mononuclear Nonheme Iron Catalysts

(2009) Jihae Yoon et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Metalloporphyrin-based oxidation systems: from biomimetic reactions to application in organic synthesis

(2009) Chi-Ming Che et al.   CHEMICAL COMMUNICATIONS

Metabolites in Safety Testing (MIST): Considerations of Mechanisms of Toxicity with Dose, Abundance, and Duration of Treatment

(2009) Dennis A. Smith et al.   CHEMICAL RESEARCH IN TOXICOLOGY

The impact of aromatic ring count on compound developability – are too many aromatic rings a liability in drug design?

(2009) Timothy J. Ritchie et al.   DRUG DISCOVERY TODAY

Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success

(2009) Frank Lovering et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Highly Reactive P450 Model Compound I

(2009) Seth R. Bell et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Toluene and Ethylbenzene Aliphatic C−H Bond Oxidations Initiated by a Dicopper(II)-μ-1,2-Peroxo Complex

(2009) Heather R. Lucas et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Pd(II)-Catalyzed Hydroxylation of Arenes with 1 atm of O2or Air

(2009) Yang-Hui Zhang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Metabolic Soft Spot Identification and Compound Optimization in Early Discovery Phases Using MetaSite and LC-MS/MS Validation

(2008) Markus Trunzer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Chemo-enzymatic fluorination of unactivated organic compounds

(2008) Andrea Rentmeister et al.   Nature Chemical Biology

New Recoverable Organoselenium Catalyst for Hydroperoxide Oxidation of Organic Substrates

(2008) Halina Wójtowicz et al.   SYNTHETIC COMMUNICATIONS