Article
Chemistry, Organic
Shuheng Xu, Linwei Zeng, Sunliang Cui
Summary: The Diels-Alder (DA) reaction and hetero-Diels-Alder (HDA) reaction are powerful methods for constructing carbocycles and heterocycles. This study presents an integrated building block that combines both DA and HDA reactions, utilizing triazenyl dienes to undergo the DA reaction and the newly released alkene moiety and triazene to engage in the HDA reaction.
Article
Chemistry, Multidisciplinary
Khaled Youssef, Magali Allain, Thomas Cauchy, Frederic Gohier
Summary: 2-Bromo, 3-bromothiophene, 2,5-dibromothiophene, 3,4-dibromothiophene, and perbrominated thiophene were oxidized under different conditions to form thiophene S,S-dioxide. Depending on the substitution, sulfone was obtained when the hindered thiophene was used. However, monosubstituted thiophenes could not be transformed into sulfone due to the reactivity of the sulfoxide intermediate, which led to dimerization. The structures were confirmed through the obtaining of crystals. The oxidation of 3,4-dibromothiophene could either result in the formation of cycloadduct or the isolation of sulfone, which could further evolve into benzothiophene sulfone.
NEW JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Organic
Jonathan P. Knowles, Hannah G. Steeds, Maria Schwarz, Francesca Latter, Kevin Booker-Milburn
Summary: This method transforms simple starting materials into complex tetracyclic products with potential medicinal chemistry applications through a sophisticated chemical catalysis process.
Article
Chemistry, Organic
Yan Jiang, Hao-Jie Ma, Xue-Long Wang, Yi Yang
Summary: A Yb(OTf)(3)-catalyzed formal (4 + 3) cycloaddition reaction was successfully achieved using donor-acceptor cyclopropanes and 3-benzylideneindoline-2-thiones as reactants. Functionalized 5,10-dihydro-2H-thiepino[2,3-b]indole derivatives were synthesized with good yields and moderate to good diastereoselectivity. This reaction represents the first (4 + 3) cycloaddition of 3-benzylideneindoline-2-thiones.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Lik Chun Wu, Guillaume De Bo
Summary: Mechanosensitive molecules are activated upon elongation of anchored polymer arms in polymer mechanochemistry. The reactivity of mechanophores is influenced by structural factors, including stereoelectronic effects in force-accelerated Diels-Alder reactions. The presence of an electron-donating heteroatom on the diene and the position of the anchor group affect activation force and reactivity.
Article
Chemistry, Organic
Yan Jiang, Hao-Jie Ma, Xue-Long Wang, Yi Yang
Summary: A new compound was synthesized successfully in this study by using Yb-(OTf)(3) catalyst to react donor-acceptor cyclopropanes with sulfur-containing 4π components. The reaction showed high yields and moderate to good diastereoselectivity.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Polymer Science
Paul van den Tempel, Emiel O. van der Boon, Jozef G. M. Winkelman, Antonina V. Krasnikova, Daniele Parisi, Peter J. Deuss, Francesco Picchioni, Ranjita K. Bose
Summary: The furan-maleimide Diels-Alder chemistry is a useful tool for designing thermo-reversible click networks. In this study, a new reaction in furan-maleimide click networks, called the Double-Diels-Alder reaction (DDA), was reported. This reaction forms extra linkages between Diels-Alder adducts and non-reacted furan groups, resulting in stronger materials but reducing thermal recycling efficiency. The study revealed that the DDA reaction can occur in both intramolecular and intermolecular fashion, and it exhibits reversibility like the regular Diels-Alder reaction. The importance of the DDA reaction in furan-maleimide click networks may be easily overlooked, leading to unexpected reactivity in these systems.
Article
Chemistry, Multidisciplinary
Yoshifumi Hashikawa, Hui Li, Yasujiro Murata
Summary: This study focuses on the Diels-Alder reaction of C-60 with azines, providing important insights into the formation of bisfulleroids. The benzoannulation to the pyridazine ring resulted in significantly shortened reaction time and better interaction with C-60. Contrary to expectations, the benzobisfulleroid was converted into corresponding orifice-enlarged derivative slightly faster through photooxygenation.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Organic
Matteo Lanzi, Racha Abed Ali Abdine, Maxime De Abreu, Joanna Wencel-Delord
Summary: This study reported the synthesis of dissymetric 2,3,2',3',4-substituted biaryls via pericyclic reactions of cyclic diaryl lambda(3)-bromanes. The method provides functional group tolerance and atom economy, allowing access to molecular complexity in a single reaction step. Continuous flow protocol has been designed for scale-up, while postfunctionalizations have been developed leveraging the residual Br-atom.
Review
Biochemistry & Molecular Biology
Maria I. L. Soares, Ana L. Cardoso, Teresa M. V. D. Pinho E. Melo
Summary: This review provides insights into the recent advances in sustainable Diels-Alder reactions since 2010, with a focus on various environmentally benign solvent systems. The scope, efficiency, selectivity, and reaction mechanism of these reaction media are discussed.
Article
Chemistry, Multidisciplinary
Jinzhao Ji, Jinying Yuan, Yen Wei
Summary: This study demonstrates the use of customized aggregation-induced emission luminogens for visualizing heterogeneous catalytic organic reactions and enabling catalyst screening. The retro-Diels-Alder reaction was used as a model reaction, with montmorillonite K10 identified as the best catalyst through screening.
CHEMICAL COMMUNICATIONS
(2022)
Article
Multidisciplinary Sciences
Andrew V. Kelleghan, Ana S. Bulger, Dominick C. Witkowski, Neil K. Garg
Summary: Since 1825, compounds with the molecular formula C6H6, especially benzene, have been extensively studied. However, the strained isomer 1,2,3-cyclohexatriene has been largely overlooked. This study demonstrates that 1,2,3-cyclohexatriene and its derivatives can undergo various reactions and be integrated into multistep syntheses, showing potential application in the synthesis of important compounds.
Article
Chemistry, Multidisciplinary
Nicole Houszka, Hannes Mikula, Dennis Svatunek
Summary: 1,2,4,5-Tetrazines are widely used in bioorthogonal chemistry for their high reactivity in Diels-Alder reactions. The substituents in the 3- and 6-positions of the tetrazine scaffold significantly affect the rate of cycloadditions, but this is not explained by frontier molecular orbital interactions. Instead, the high reactivity of mono-substituted tetrazines is due to decreased Pauli repulsion, leading to a more asynchronous approach and reduced distortion energy. Additionally, ethylene is not a good model compound for other alkenes in Diels-Alder reactions.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Physical
Wakana Sakai, Lori Gonnet, Naoki Haruta, Tohru Sato, Michel Baron
Summary: This study theoretically explains the factors that control the mechanochemical reactivities using Diels-Alder reactions as an example. The introduction of dimensionless mechanochemical reaction constants allows for the comparison of different reactions.
PHYSICAL CHEMISTRY CHEMICAL PHYSICS
(2024)
Article
Chemistry, Multidisciplinary
Sheng Li, Xinqiao Wang, Yejian Wu, Hongliang Duan, Lan Tang
Summary: In this study, a GAN was used as a generative model for the generation of Diels-Alder reactions. The model successfully learned reaction rules and generated novel reactions, showing the potential of GANs in the field of organic chemistry.
Article
Chemistry, Physical
Leela S. Dodda, Julian Tirado-Rives, William L. Jorgensen
JOURNAL OF PHYSICAL CHEMISTRY B
(2019)
Article
Chemistry, Physical
Michael J. Robertson, Yue Qian, Matthew C. Robinson, Julian Tirado-Rives, William L. Jorgensen
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2019)
Article
Chemistry, Physical
Israel Cabeza de Vaca, Ricardo Zarzuela, Julian Tirado-Rives, William L. Jorgensen
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2019)
Article
Chemistry, Physical
Julian Tirado-Rives, William L. Jorgensen
JOURNAL OF PHYSICAL CHEMISTRY A
(2019)
Article
Chemistry, Physical
Yue Qian, Israel Cabeza de Vaca, Jonah Z. Vilseck, Daniel J. Cole, Julian Tirado-Rives, William L. Jorgensen
JOURNAL OF PHYSICAL CHEMISTRY B
(2019)
Article
Chemistry, Medicinal
D. J. Czyzyk, M. Valhondo, L. Deiana, J. Tirado-Rives, W. L. Jorgensen, K. S. Anderson
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Chemistry, Medicinal
Kara J. Cutrona, Ana S. Newton, Stefan G. Krimmer, Julian Tirado-Rives, William L. Jorgensen
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2020)
Article
Chemistry, Physical
Aysegul Turupcu, Julian Tirado-Rives, William L. Jorgensen
JOURNAL OF CHEMICAL THEORY AND COMPUTATION
(2020)
Article
Chemistry, Medicinal
Mohammad M. Ghahremanpour, Julian Tirado-Rives, Maya Deshmukh, Joseph A. Ippolito, Chun-Hui Zhang, Israel Cabeza de Vaca, Maria-Elena Liosi, Karen S. Anderson, William L. Jorgensen
ACS MEDICINAL CHEMISTRY LETTERS
(2020)
Article
Chemistry, Multidisciplinary
Chun-Hui Zhang, Elizabeth A. Stone, Maya Deshmukh, Joseph A. Ippolito, Mohammad M. Ghahremanpour, Julian Tirado-Rives, Krasimir A. Spasov, Shuo Zhang, Yuka Takeo, Shalley N. Kudalkar, Zhuobin Liang, Farren Isaacs, Brett Lindenbach, Scott J. Miller, Karen S. Anderson, William L. Jorgensen
Summary: Starting from known drugs, the study redesigned perampanel into potent noncovalent inhibitors of SARS-CoV-2 main protease with ca. 20 nM IC50 values. Free-energy perturbation calculations and high-resolution X-ray crystal structures guided the design efforts and rapid development of effective analogues. Cell-based antiviral assays confirmed the potential of the compounds for COVID-19 treatment, highlighting the power of computational chemistry in drug discovery.
ACS CENTRAL SCIENCE
(2021)
Article
Chemistry, Medicinal
Chun-Hui Zhang, Krasimir A. Spasov, Raquel A. Reilly, Klarissa Hollander, Elizabeth A. Stone, Joseph A. Ippolito, Maria-Elena Liosi, Maya G. Deshmukh, Julian Tirado-Rives, Shuo Zhang, Zhuobin Liang, Scott J. Miller, Farren Isaacs, Brett D. Lindenbach, Karen S. Anderson, William L. Jorgensen
Summary: New non-covalent inhibitors targeting the main protease of SARS-CoV-2 have shown improved potency and cell permeability, with some compounds demonstrating promising potential as therapies for COVID-19.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Chemistry, Physical
Mohammad M. Ghahremanpour, Julian Tirado-Rives, William L. Jorgensen
Summary: By refining the torsion and Lennard-Jones parameters of the OPLS force field, the thermodynamics and dynamics of various liquid alkanes can be accurately described. The modified force field (OPLS/2020) shows improved performance for long-chain alkanes, with average errors significantly reduced for computed properties such as liquid densities, heats of vaporization, and free energies of hydration. The new force field is suitable for improved modeling of numerous systems in chemistry, biology, and materials science.
JOURNAL OF PHYSICAL CHEMISTRY B
(2022)
Article
Chemistry, Medicinal
Mohammad M. Ghahremanpour, Anastasia Saar, Julian Tirado-Rives, William L. Jorgensen
Summary: Accurate calculation of absolute binding free energies (ABFEs) for protein-ligand complexes is crucial in computer-aided drug design. In this study, a high-quality dataset of 16 inhibitors of SARS-CoV-2 main protease with diverse structures and well-distributed BFEs was selected. The ABFE results obtained from 2 μs molecular dynamics simulations using free energy perturbation theory showed promising correlation with experimental results, indicating the potential of current FEP-based calculations for identification of active compounds.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Medicinal
Mohammad M. Ghahremanpour, Anastasia Saar, Julian Tirado-Rives, William L. Jorgensen
Summary: Geometric deep learning, a powerful tool for predicting molecular properties, is used to improve the pharmacokinetics of drug candidates by accurately predicting aqueous solubility. Two ensembles of graph neural network architectures were built and pretrained models demonstrated significantly better performance than existing neural networks. The inclusion of atomic attributes further improved the prediction of aqueous solubility.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Meeting Abstract
Chemistry, Multidisciplinary
Israel Cabeza de Vaca, Yue Qian, Jonah Vilseck, Julian Tirado-Rives, William Jorgensen
ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY
(2018)