Article
Chemistry, Multidisciplinary
Huy Tran, Guillaume Revol, Alyson Poyser, Louis Barriault
Summary: In this study, a novel Lewis acid gold catalyst was used to generate synthetically challenging polycyclic scaffolds through a one-pot cascade sequence. By controlling the ligand and reaction conditions, both 6,6,5-tricyclic and 6,6,6,5-tetracyclic cores were selectively synthesized in one operation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Derek J. Essegian, Tyler A. Cunningham, Christopher J. Zerio, Eli Chapman, Jonathan Schatz, Stephan C. Schurer
Summary: This study comprehensively analyzed the conformational changes of eIF4A1 using protein-ligand docking, homology modeling, and extended molecular dynamics simulations. A novel phenyl-piperazine pharmacophore was discovered, predicted to target the ATP-binding site and potentially serve as the starting point for medicinal chemistry optimization efforts. This is the first report of an ATP-competitive inhibitor for eiF4A1, which is predicted to bind in the nucleotide cleft.
Article
Chemistry, Medicinal
Chloe Townley, Lindsay McMurray, Stephen P. Marsden, Adam Nelson
Summary: A top-down synthetic approach was used to efficiently synthesize 21 diverse novel molecular scaffolds, which were derived from complex intermediates prepared using cycloaddition chemistry. Scaffold-hopping of these intermediates was achieved through ring attachment, cleavage, expansion, and/or fusion, leading to the generation of diverse lead-like screening compounds.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Organic
Austin D. Marchese, Andrew G. Durant, Mark Lautens
Summary: A simple and modular approach using palladium catalysis to synthesize bis-heterocyclic spirocycles is reported. The method leverages a Mizoroki-Heck-type reaction to generate neopentylpalladium species, allowing for intramolecular C-H activation on a wide array of C-H bonds to produce a variety of spirocycles. The reaction is scalable, allowing for easy incorporation of biologically relevant heterocycles without the need for flash column chromatography.
Article
Chemistry, Multidisciplinary
Dario Corbisiero, Tommaso Fantoni, Lucia Ferrazzano, Giulia Martelli, Paolo Cantelmi, Alexia Mattellone, Chiara Palladino, Magda Monari, Riccardo Pedrazzani, Alessandra Tolomelli, Walter Cabri
Summary: The enantioselective 1,3-dipolar cycloaddition of nitrones and arylpropionaldehydes was studied to generate highly functionalized scaffolds for drug discovery. The use of a second-generation MacMillan catalyst as hydrochloride salt accelerated the reaction speed and yielded 4-isoxazolines with good to excellent enantiomeric ratios at room temperature. Further functionalization of the isoxazoline core through Pd-catalyzed cross-coupling generated differently functionalized chemical architectures in high yield.
Article
Chemistry, Multidisciplinary
Timothe Maujean, Prakash Kannaboina, Adam I. Green, George M. Burslem
Summary: We developed a simple and rational method to rank lead-likeness of molecules using continuous evaluation functions, which has proven to be competitive against known methods and has helped in selecting promising candidate molecules for epigenetic applications.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Khadijah Anwar, Francisco Jose Aguilar Troyano, Ayham H. Abazid, Oumayma El Yarroudi, Ignacio Funes-Ardoiz, Adrian Gomez-Suarez
Summary: Here, we present a highly modular strategy for synthesizing spirocyclic scaffolds from easily available starting materials, such as cyclic ketones and alpha-amino or oxamic acids. The reaction involves a simple Knoevenagel condensation, followed by a cascade Giese-type reaction and base-mediated cyclization, resulting in a wide range of polar spirocyclic products in high yields. Our method allows for easy diversification of the products, thus providing rapid access to libraries of potential drug-like molecules.
Article
Chemistry, Medicinal
Priyanka Yadav, Chander Prakash Kaushik, Archna Yadav, Jyoti Yadav, Dharmendra Singh
Summary: The aim of this study was to design and synthesize diverse piperazine-1,2,3-triazole scaffolds as key pharmacophores with antimicrobial/anticancer activities. Twenty-four scaffolds were synthesized via a click-inspired synthetic protocol and were evaluated for anticancer activity and antimicrobial potency. The results showed that compounds 7i and 7a exhibited good anticancer activity, and compound 7x showed notable antimicrobial activity. Molecular docking studies were conducted to investigate the binding interactions of potent analogs 7i and 7a. Compound 7x is considered a valuable lead compound for further optimization of anticancer and antimicrobial agents.
FUTURE MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Bing-Bing Wu, Jie Xu, Qian Gao, Kang-Jie Bian, Guo-Kai Liu, Xi-Sheng Wang
Summary: In this study, a general and efficient method for preparing diverse aliphatic monofluorides was reported using monofluoroalkyl triflate as the synthetic scaffold. The broad utility of this monofluoroalkylating reagent was demonstrated through nickel-catalyzed hydromonofluoroalkylation and copper-catalyzed C-C bond formation.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Jingwen Wei, Yangyang Xing, Xiaohan Ye, Bao Nguyen, Lukasz Wojtas, Xin Hong, Xiaodong Shi
Summary: In this study, a new synthetic strategy for enantioselective 1,2-dihydropyridine synthesis was reported. Using the gold-catalyzed intermolecular condensation of amine and diyne-ene, the synthesis was achieved through a formal [3+2+1] fashion with up to 95% yield and up to 99% enantiomeric excess (e.e.).
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Hongyuan Fu, Ming Zhang, Youdi Zhang, Qingyuan Wang, Zheng'ao Xu, Qiuju Zhou, Zhengkai Li, Yang Bai, Yongfang Li, Zhi-Guo Zhang
Summary: In this study, a simple and cost-effective solution to the challenge of synthesizing giant molecule acceptors (GMAs) for stable polymer solar cells was presented. The Lewis acid-catalyzed Knoevenagel condensation with boron trifluoride etherate (BF3 center dot OEt2) as catalyst allowed for the efficient synthesis of GMAs, resulting in a high device efficiency of over 18%.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Jiabin Ni, Xiaowen Xia, Danyu Gu, Zhaobin Wang
Summary: In this study, a Ti-catalyzed modular ketone synthesis from carboxylic derivatives and easily accessed gem-dihaloalkanes is described. Notably, this protocol enables the direct catalytic olefination of carboxylic acids. The method features a sequence of olefination and electrophilic transformation, exhibits good functional group compatibility, and allows rapid access to various functionalized ketones. Preliminary mechanistic studies support the intermediacy of plausible alkylidene titanocene and gem-bimetallic complexes.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Suchen Zou, Zeyu Zhao, Hanmin Huang
Summary: In this study, a novel and efficient palladium-catalyzed reaction was developed for the regioselective and stereodivergent ring-closing of aminoenynes with aldehydes and boronic acids or hydrosilane. The reaction allows for the synthesis of a series of exocyclic 1,3-dienes bearing saturated N-heterocycles of 5- to 8-membered rings. It utilizes a simple Pd-catalyst and works under mild reaction conditions with a broad range of substrates. The resulting products serve as useful intermediates for chemical synthesis due to the versatility of the conjugated diene. Preliminary mechanistic details of the reaction are also uncovered.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Nikolaos Kaplaneris, Jongwoo Son, Lorena Mendive-Tapia, Adelina Kopp, Nicole D. Barth, Isaac Maksso, Marc Vendrell, Lutz Ackermann
Summary: Bioorthogonal diversification of peptides usually relies on impractical prefunctionalization methods. The authors have developed a manganese(I)-catalyzed C-H fluorescent labeling with BODIPY probes, which enables the development of activatable fluorophores for imaging cell function.
NATURE COMMUNICATIONS
(2021)
Article
Chemistry, Physical
Ting Yu, Zhong-Qiu Li, Jing Li, Sidi Cheng, Jiali Xu, Jun Huang, Yu-Wu Zhong, Shuang Luo, Qiang Zhu
Summary: Enantioenriched pyrido[6]helicenes and furan-containing pyrido[7]helicenes have been synthesized through a palladium-catalyzed double imidoylative cyclization. This method allows for the construction of two pyridyl rings in one pot, leading to structurally diverse optically pure pyridohelicenes. This research provides potential for optical studies and applications of this important class of azahelicenes.
Article
Chemistry, Organic
Shiao Chow, Adam I. Green, Christopher Arter, Samuel Liver, Abbie Leggott, Luke Trask, George Karageorgis, Stuart Warriner, Adam Nelson
SYNTHESIS-STUTTGART
(2020)
Article
Chemistry, Multidisciplinary
Adam I. Green, Fruzsina Hobor, Christopher P. Tinworth, Stuart Warriner, Andrew J. Wilson, Adam Nelson
CHEMISTRY-A EUROPEAN JOURNAL
(2020)
Article
Chemistry, Medicinal
George Karageorgis, Samuel Liver, Adam Nelson
Article
Chemistry, Multidisciplinary
Adam I. Green, Christopher P. Tinworth, Stuart Warriner, Adam Nelson, Natalie Fey
Summary: Dirhodium(II) catalysts have diverse properties, and a database based on DFT-calculated parameters has been developed to aid in catalyst selection and exploration of reactivity.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Anthony Aimon, Mark J. Dow, Abigail R. Hanby, Ephraim A. Okolo, Christopher M. Pask, Adam Nelson, Stephen P. Marsden
Summary: The stereocontrolled synthesis of complex spirotricyclic systems containing an embedded syn-1,2-diaminocyclohexane unit is achieved through a dearomatising oxidation of phenols bearing pendant ureas capable of acting as double nucleophiles. The resultant products possess rich functionality suitable for the synthesis of potentially bioactive compounds.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Ephraim A. Okolo, Axel Pahl, Sonja Sievers, Christopher M. Pask, Adam Nelson, Stephen P. Marsden
Summary: A 'top down' scaffold remodelling approach was used to synthesize a library of spirotricyclic ureas via complexity-generating oxidative dearomatisation. Eighteen structurally distinct, sp(3)-rich scaffolds were obtained from the parent tricycle through ring addition, cleavage, and expansion strategies. Biological screening of the compound library based on these scaffolds revealed diverse phenotypic responses, highlighting both functional and structural diversity of the compounds.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Alexandra Hindle, Krzysztof Baj, Jonathan A. Iggo, Daniel J. Cox, Christopher M. Pask, Adam Nelson, Stephen P. Marsden
Summary: A convergent approach to diazabicyclic scaffolds containing twisted amides or anilines is achieved through photocatalysed hydroamination and subsequent cyclisation of cyclic enecarbamates. The modular synthesis enables variation of the degree of twist and consequently the properties of the amides and anilines.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Organic
Daniel Francis, Sannia Farooque, Archie Meager, Didi Derks, Abbie Leggott, Stuart Warriner, Alex J. O'Neill, Adam Nelson
Summary: Activity-directed synthesis (ADS) is a function-driven method for discovering bioactive small molecules. In this study, algorithms were developed to design arrays of photoredox-catalysed alkylation reactions based on similarity to known bioactive reactions. The approach successfully expanded a series of antibacterial quinazolinones.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Kristina Hetherington, Som Dutt, Amaurys A. Ibarra, Emma E. Cawood, Fruzsina Hobor, Derek N. Woolfson, Thomas A. Edwards, Adam Nelson, Richard B. Sessions, Andrew J. Wilson
Summary: The study introduces a computationally validated workflow for modifying the sequence of peptide inhibitors of protein-protein interactions.
RSC CHEMICAL BIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Sergio Celis, Fruzsina Hobor, Thomas James, Gail J. Bartlett, Amaurys A. Ibarra, Deborah K. Shoemark, Zsofia Hegedus, Kristina Hetherington, Derek N. Woolfson, Richard B. Sessions, Thomas A. Edwards, David M. Andrews, Adam Nelson, Andrew J. Wilson
Summary: The study presents a general approach to discover orthosteric PPI inhibitors that mimic specific secondary protein structures, validated through experimental examples. Low μM activity selective PPI inhibitors were discovered for two unrelated PPIs, with defined structure-activity relationships established through hit expansion. The approach is believed to have the potential to enable the discovery of inhibitors for a wide range of unrelated secondary structure-mediated PPIs.
Article
Chemistry, Multidisciplinary
Samuel D. Griggs, Alejandro Martin-Roncero, Adam Nelson, Stephen P. Marsden
Summary: This study reports a regioselective gamma-C-H amination method for the side-chain of saturated 2-alkyl nitrogen heterocycles, which proceeds through a sulfamide-directed 1,6-radical translocation. The practicality of this rapid access to 1,3-diamines is highlighted in a short synthesis of the alkaloid tetraponerine T8 and non-natural analogues.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Scott Rice, Daniel J. Cox, Stephen P. Marsden, Adam Nelson
Summary: Regioselective and stereospecific directed C-H arylation of simple amine substrates, followed by cyclisation, resulted in the synthesis of 30 diverse, three-dimensional scaffolds. This unified approach significantly expanded the range of bridged ring systems containing both a nitrogen atom and an aromatic ring.
CHEMICAL COMMUNICATIONS
(2021)
Review
Biochemistry & Molecular Biology
Adam Nelson, George Karageorgis
Summary: This minireview discusses methods that draw inspiration from natural products to focus on biologically-relevant areas of chemical space, potentially leading to more systematic discovery of unexplored regions in biologically-relevant chemical space.
RSC MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Alexandre F. Trindade, Emily L. Faulkner, Andrew G. Leach, Adam Nelson, Stephen P. Marsden
CHEMICAL COMMUNICATIONS
(2020)
Article
Chemistry, Multidisciplinary
Abbie Leggott, Justin E. Clarke, Shiao Chow, Stuart L. Warriner, Alex J. O'Neill, Adam Nelson
CHEMICAL COMMUNICATIONS
(2020)
