Organic Process Research & Development
DOI: 10.1021/acs.oprd.1c00092
James Sanderson
Shared posts
25 May 09:28
[ASAP] Scale-Up and Optimization of a Continuous Flow Carboxylation of N-Boc-4,4-difluoropiperidine Using s-BuLi in THF
by Jean-Paul Kestemont, James R. Frost, Jérôme Jacq, Patrick Pasau, Frédéric Perl, Julien Brown, and Matthieu Tissot
23 Apr 10:01
[ASAP] From Bench to Plant: An Opportunity for Transition Metal Paired Electrocatalysis
by Julien C. Vantourout
Organic Process Research & Development
DOI: 10.1021/acs.oprd.1c00046
26 Mar 10:25
[ASAP] Physiological Functions of Bacterial “Multidrug” Efflux Pumps
by Peter J. F. Henderson, Claire Maher, Liam D. H. Elbourne, Bart A. Eijkelkamp, Ian T. Paulsen, and Karl A. Hassan
Chemical Reviews
DOI: 10.1021/acs.chemrev.0c01226
chemosphere likes this
26 Mar 10:21
[ASAP] The Alpha Keto Amide Moiety as a Privileged Motif in Medicinal Chemistry: Current Insights and Emerging Opportunities
by Marco Robello, Elisabetta Barresi, Emma Baglini, Silvia Salerno, Sabrina Taliani, and Federico Da Settimo
Journal of Medicinal Chemistry
DOI: 10.1021/acs.jmedchem.0c01808
januswen likes this
11 Jan 07:18
[ASAP] Carbonyl Desaturation: Where Does Catalysis Stand?
by Samer Gnaim, Julien C. Vantourout, Fabien Serpier, Pierre-Georges Echeverria, and Phil. S. Baran
ACS Catalysis
DOI: 10.1021/acscatal.0c04712
11 Jan 06:43
[ASAP] Iron-Catalyzed Triazole-Enabled C–H Activation with Bicyclopropylidenes
by Jiayu Mo, Antonis M. Messinis, João C. A. Oliveira, Serhiy Demeshko, Franc Meyer, and Lutz Ackermann
ACS Catalysis
DOI: 10.1021/acscatal.0c04748
Eduardo Da Concepción likes this
02 Jan 10:15
[ASAP] Spirocyclic Scaffolds in Medicinal Chemistry
by Kerstin Hiesinger, Dmitry Dar’in, Ewgenij Proschak, and Mikhail Krasavin
Journal of Medicinal Chemistry
DOI: 10.1021/acs.jmedchem.0c01473
Nfourber likes this
24 Dec 12:03
Safe, Scalable, Inexpensive, and Mild Nickel‐Catalyzed Migita‐Like C−S Cross‐Couplings in Recyclable Water
by Tzu‐Yu Yu,
Haobo Pang,
Yilin Cao,
Fabrice Gallou,
Bruce H. Lipshutz
Aryl sulfides are easily made in water under mild conditions using a ligated base‐metal catalyst. A new Ni‐catalyzed C−S bond formation leading to functionalized products can now be obtained in good yields, with residual levels of metal contamination below FDA guidelines without additional processing.
Abstract
A new approach to C−S couplings is reported that relies on nickel catalysis under mild conditions, enabled by micellar catalysis in recyclable water as the reaction medium. The protocol tolerates a wide range of heteroaromatic halides and thiols, including alkyl and heteroaryl thiols, leading to a variety of thioethers in good isolated yields. The method is scalable, results in low residual metal in the products, and is applicable to syntheses of targets in the pharmaceutical area. The procedure also features an associated low E Factor, suggesting a far more attractive entry than is otherwise currently available, especially those based on unsustainable loadings of Pd catalysts.
24 Dec 11:25
[ASAP] Chlorinated Solvents: Their Advantages, Disadvantages, and Alternatives in Organic and Medicinal Chemistry
by Andrew Jordan, Patrick Stoy, and Helen F. Sneddon
Chemical Reviews
DOI: 10.1021/acs.chemrev.0c00709
James Wood, Rubén and 2 others like this
24 Dec 11:15
Enzymatic Kinetic Resolution by Addition of Oxygen
by Lucy A. Harwood,
Luet L. Wong,
Jeremy Robertson
Enzymatic oxidative kinetic resolutions (OKR), in which a new oxygen atom is inserted into the substrate, are highly effective for the synthesis of enantioenriched oxygen‐containing compounds. This Minireview discusses selected enzyme classes that can achieve OKR, biological advancements and protein development, and the use of these key enantioenriched intermediates in natural product synthesis.
Abstract
Kinetic resolution using biocatalysis has proven to be an excellent complementary technique to traditional asymmetric catalysis for the production of enantioenriched compounds. Resolution using oxidative enzymes produces valuable oxygenated structures for use in synthetic route development. This Minireview focuses on enzymes which catalyse the insertion of an oxygen atom into the substrate and, in so doing, can achieve oxidative kinetic resolution. The Baeyer–Villiger rearrangement, epoxidation, and hydroxylation are included, and biological advancements in enzyme development, and applications of these key enantioenriched intermediates in natural product synthesis are discussed.
11 Dec 07:09
Introducing tox‐Profiles of Chemical Reactions
by Ksenia S. Egorova,
Alexey S. Galushko,
Valentine P. Ananikov
In this Essay we propose tox‐Profiles of chemical reactions to eliminate misleading preconceptions about the biological activity of organic molecules and to stimulate further progress in the field. tox‐Profiles can be used to classify synthetic reactions, manage the biological activity of molecules, and guide the rational development of new methodologies.
Abstract
In this Essay, we present a critical analysis of two common practices in modern chemistry—that is, of using speculations about the “greenness” and “nontoxicity” of developed synthesis procedures and of a priori labelling various compounds derived from natural sources as being environmentally safe. We note that every organic molecule that contains functional groups should be biologically active. Thus, analysis of the particular greenness and the potential environmental impact of a given chemical process should account for the biological activity of all its components in a measureable (rather than empirical) way. We highlight the necessity of clarifying discussions on biological activity and toxicity and propose possible ways of introducing tox‐Profiles as a reliable overview of the overall toxicity of chemical reactions.
lichenliu1991 likes this
29 Nov 10:10
[ASAP] Fragment-to-Lead Medicinal Chemistry Publications in 2019
by Wolfgang Jahnke, Daniel A. Erlanson, Iwan J. P. de Esch, Christopher N. Johnson, Paul N. Mortenson, Yuji Ochi, and Tatsuya Urushima
Journal of Medicinal Chemistry
DOI: 10.1021/acs.jmedchem.0c01608
29 Nov 09:39
[ASAP] Improvement in the Palladium-Catalyzed Miyaura Borylation Reaction by Optimization of the Base: Scope and Mechanistic Study
by Santiago Barroso, Markus Joksch, Pim Puylaert, Sergey Tin, Stephen J. Bell, Luke Donnellan, Stewart Duguid, Colin Muir, Peichao Zhao, Vittorio Farina, Duc N. Tran, and Johannes G. de Vries
The Journal of Organic Chemistry
DOI: 10.1021/acs.joc.0c01758
29 Nov 09:39
Open Access
  This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.
Probing conformational hotspots for the recognition and intervention of protein complex by lysine reactivity profiling
Chem. Sci., 2021, Accepted Manuscript
DOI: 10.1039/D0SC05330A, Edge Article
DOI: 10.1039/D0SC05330A, Edge Article
Open Access  This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence.
Zheyi Liu, Wenxiang Zhang, Binwen Sun, Yaolu Ma, Min He, Yuanjiang Pan, Fangjun Wang
Probing the conformational and functional hotspot sites within aqueous native protein complexes is still a challenging task. Herein, a mass spectrometry (MS)-based two-step isotope labeling-lysine reactivity profiling (TILLRP) strategy is...
The content of this RSS Feed (c) The Royal Society of Chemistry
Probing the conformational and functional hotspot sites within aqueous native protein complexes is still a challenging task. Herein, a mass spectrometry (MS)-based two-step isotope labeling-lysine reactivity profiling (TILLRP) strategy is...
The content of this RSS Feed (c) The Royal Society of Chemistry
14 Nov 19:59
Design and Scalable Synthesis of N‐Alkylhydroxylamine Reagents for the Direct Iron‐Catalyzed Installation of Medicinally Relevant Amines**
by Eric Falk,
Szabolcs Makai,
Tristan Delcaillau,
Laura Gürtler,
Bill Morandi
The direct synthesis of unprotected secondary and tertiary alkylamines from alkenes is reported. Aminative difunctionalization was mediated by an iron catalyst to yield a family of ten hydroxylamine‐derived aminating reagents. Several medicinally relevant amine groups, such as methylamine, morpholine and piperazine, were installed through the aminochlorination, ‐hydroxylation, ‐azidation and carboamination of alkenes.
Abstract
Secondary and tertiary alkylamines are privileged substance classes that are often found in pharmaceuticals and other biologically active small molecules. Herein, we report their direct synthesis from alkenes through an aminative difunctionalization reaction enabled by iron catalysis. A family of ten novel hydroxylamine‐derived aminating reagents were designed for the installation of several medicinally relevant amine groups, such as methylamine, morpholine and piperazine, through the aminochlorination of alkenes. The method has excellent functional group tolerance and a broad scope of alkenes was converted to the corresponding products, including several drug‐like molecules. Besides aminochlorination, the installation of other functionalities through aminoazidation, aminohydroxylation and even intramolecular carboamination reactions, was demonstrated, further highlighting the broad potential of these new reagents for the discovery of novel amination reactions.
Seb likes this
14 Nov 19:51
[ASAP] Ruthenium-Catalyzed Ester Reductions Applied to Pharmaceutical Intermediates
by Youssef Shaalan, Lee Boulton, and Craig Jamieson
Organic Process Research & Development
DOI: 10.1021/acs.oprd.0c00410
06 Nov 07:14
[ASAP] Complex Crystal Structures of EGFR with Third-Generation Kinase Inhibitors and Simultaneously Bound Allosteric Ligands
by Janina Niggenaber, Leonie Heyden, Tobias Grabe, Matthias P. Müller, Jonas Lategahn, and Daniel Rauh
ACS Medicinal Chemistry Letters
DOI: 10.1021/acsmedchemlett.0c00472
04 Nov 07:18
[ASAP] Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2
by Mohammad M. Ghahremanpour, Julian Tirado-Rives, Maya Deshmukh, Joseph A. Ippolito, Chun-Hui Zhang, Israel Cabeza de Vaca, Maria-Elena Liosi, Karen S. Anderson, and William L. Jorgensen
ACS Medicinal Chemistry Letters
DOI: 10.1021/acsmedchemlett.0c00521
23 Oct 06:08
Minisci C−H Alkylation of Heteroarenes Enabled by Dual Photoredox/Bromide Catalysis in Micellar Solutions**
by Marilia S. Santos,
Martyna Cybularczyk‐Cecotka,
Burkhard König,
Maciej Giedyk
New and improved: The combination of microstructured aqueous solutions and photoredox catalysis allowed us to develop a new approach for Minisci reaction. The smooth C−H alkylation of the heterocycles was achieved employing non‐activated alkyl bromides and without the use of stoichiometric amounts of radical promoters. The biologically useful products were generated under neutral and basic conditions under commercially available blue LEDs.
Abstract
Aromatic heterocycles are omnipresent structural motifs in various natural products, pharmaceuticals and agrochemicals. This work describes a photocatalytic Minisci‐type C−H functionalization of heteroarenes with non‐activated alkyl bromides. The reaction avoids stoichiometric radical‐promoters, oxidants, or acids, and is conducted using blue LEDs as the light source. The reactive carbon‐centered alkyl radicals are generated by merging the photoredox approach with bromide anion co‐catalysis and spatial pre‐aggregation of reacting species in the micellar aqueous solutions. The obtained data highlight the critical importance of microstructuring and organization of the components in the reaction mixture.
19 Oct 06:09
[ASAP] Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19
by Robert L. Hoffman, Robert S. Kania, Mary A. Brothers, Jay F. Davies, Rose A. Ferre, Ketan S. Gajiwala, Mingying He, Robert J. Hogan, Kirk Kozminski, Lilian Y. Li, Jonathan W. Lockner, Jihong Lou, Michelle T. Marra, Lennert J. Mitchell, Jr., Brion W. Murray, James A. Nieman, Stephen Noell, Simon P. Planken, Thomas Rowe, Kevin Ryan, George J. Smith, III, James E. Solowiej, Claire M. Steppan, and Barbara Taggart
Journal of Medicinal Chemistry
DOI: 10.1021/acs.jmedchem.0c01063
15 Oct 06:07
[ASAP] Stereoselective Access to Azetidine-Based α-Amino Acids and Applications to Small Peptide Synthesis
by Felix Reiners, Emanuel Joseph, Benedikt Nißl, and Dorian Didier
Organic Letters
DOI: 10.1021/acs.orglett.0c03131
Bruna, Alessia Michelotti and 2 others like this
13 Oct 06:06
UV‐Induced 1,3,4‐Oxadiazole Formation from 5‐Substituted Tetrazoles and Carboxylic Acids in Flow
by Luke Green,
Keith Livingstone,
Sophie Bertrand,
Simon Peace,
Craig Jamieson
A photochemical, flow‐based Huisgen synthesis of 1,3,4‐oxadiazoles from 5‐substituted tetrazoles and carboxylic acids has been developed. This has enabled the expedient and facile synthesis of a broad palette of heterocyclic derivatives which are of direct relevance to a range of applications including pharmaceuticals and materials science (see scheme).
Abstract
A range of 1,3,4‐oxadiazoles have been synthesized using a UV‐B activated flow approach starting from carboxylic acids and 5‐substituted tetrazoles. The application of UV light represents an attractive alternative to the traditional thermolytic approach and has demonstrated comparable efficiency and versatility, with a diverse substrate scope, including the incorporation of highly substituted amino acids.
13 Oct 06:01
[ASAP] Fighting COVID-19 Using Molecular Dynamics Simulations
by Pablo R. Arantes, Aakash Saha, and Giulia Palermo
ACS Central Science
DOI: 10.1021/acscentsci.0c01236
11 Oct 11:51
[ASAP] Predicting the Human Hepatic Clearance of Acidic and Zwitterionic Drugs
by David A. Tess, Heather Eng, Amit S. Kalgutkar, John Litchfield, David J. Edmonds, David A. Griffith, and Manthena V. S. Varma
Journal of Medicinal Chemistry
DOI: 10.1021/acs.jmedchem.0c01033
08 Oct 06:18
Introducing tox‐Profiles of Chemical Reactions
by Ksenia S. Egorova,
Alexey S. Galushko,
Valentine P. Ananikov
In this Essay we propose tox‐Profiles of chemical reactions to eliminate misleading preconceptions about the biological activity of organic molecules and to stimulate further progress in the field. tox‐Profiles can be used to classify synthetic reactions, manage the biological activity of molecules, and guide the rational development of new methodologies.
Abstract
In this Essay, we present a critical analysis of two common practices in modern chemistry—that is, of using speculations about the “greenness” and “nontoxicity” of developed synthesis procedures and of a priori labelling various compounds derived from natural sources as being environmentally safe. We note that every organic molecule that contains functional groups should be biologically active. Thus, analysis of the particular greenness and the potential environmental impact of a given chemical process should account for the biological activity of all its components in a measureable (rather than empirical) way. We highlight the necessity of clarifying discussions on biological activity and toxicity and propose possible ways of introducing tox‐Profiles as a reliable overview of the overall toxicity of chemical reactions.
08 Oct 06:12
[ASAP] Thiourea-Mediated Halogenation of Alcohols
by Amar R. Mohite, Ravindra S. Phatake, Pooja Dubey, Mohamed Agbaria, Alexander I. Shames, N. Gabriel Lemcoff, and Ofer Reany
The Journal of Organic Chemistry
DOI: 10.1021/acs.joc.0c01431
08 Oct 06:04
Open Access
  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Is it time for biocatalysis in fragment-based drug discovery?
Chem. Sci., 2020, Advance Article
DOI: 10.1039/D0SC04103C, Perspective
DOI: 10.1039/D0SC04103C, Perspective
Open Access  This article is licensed under a Creative Commons Attribution 3.0 Unported Licence.
Jeremy I. Ramsden, Sebastian C. Cosgrove, Nicholas J. Turner
This perspective discusses how biocatalysis could play an important role in the future fragment-based drug discovery.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
This perspective discusses how biocatalysis could play an important role in the future fragment-based drug discovery.
To cite this article before page numbers are assigned, use the DOI form of citation above.
The content of this RSS Feed (c) The Royal Society of Chemistry
06 Oct 16:40
[ASAP] Activation of C–O and C–N Bonds Using Non-Precious-Metal Catalysis
by Timothy B. Boit, Ana S. Bulger, Jacob E. Dander, and Neil K. Garg
ACS Catalysis
DOI: 10.1021/acscatal.0c03334
QiuJ, Jean-François V-R and one other like this
06 Oct 16:12
[ASAP] Serine-Selective Bioconjugation
by Julien C. Vantourout, Srinivasa Rao Adusumalli, Kyle W. Knouse, Dillon T. Flood, Antonio Ramirez, Natalia M. Padial, Alena Istrate, Katarzyna Maziarz, Justine N. deGruyter, Rohan R. Merchant, Jennifer X. Qiao, Michael A. Schmidt, Michael J. Deery, Martin D. Eastgate, Philip E. Dawson, Gonçalo J. L. Bernardes, and Phil S. Baran
Journal of the American Chemical Society
DOI: 10.1021/jacs.0c05595
Phil, Sallustrau Antoine (Stro) and 3 others like this
06 Oct 15:34
[ASAP] Synthetic Elaboration of Native DNA by RASS (SENDR)
by Dillon T. Flood, Kyle W. Knouse, Julien C. Vantourout, Seiya Kitamura, Brittany B. Sanchez, Emily J. Sturgell, Jason S. Chen, Dennis W. Wolan, Phil S. Baran, and Philip E. Dawson
ACS Central Science
DOI: 10.1021/acscentsci.0c00680