Article
Chemistry, Physical
Mariola Zielinska-Blajet, Joanna Najdek
Summary: An efficient approach to synthesizing chiral selenoureas derived from Cinchona alkaloid scaffolds was described in this study. These selenoureas were evaluated as bifunctional organocatalysts in asymmetric Michael addition reactions, with the best results achieved by those containing the 4-fluorophenyl group, showing enantioselectivities up to 96% ee. Additionally, the catalytic performance of thiourea and selenourea counterparts was compared.
Article
Chemistry, Organic
Feng Jiang, Tengfei Meng, Ying Zhou, Zhenying Xiong, Yupei Zhao, Wengang Guo
Summary: We report an enantio- and diastereodivergent synthesis of enantioenriched fluorenes with broad substrate scope and high enantioselectivity (up to 99% ee) under low catalyst loading (0.1 mol %). The success of this method lies in the pseudo-diastereodivergent desymmetrization of stereoisomers of meso-epoxides enabled by the same organocatalyst. Furthermore, some of the chiral fluorenes obtained exhibit high fluorescence quantum yields (up to 76.6%), as evidenced by photophysical properties studies.
Article
Chemistry, Applied
Ken Okuno, Bun Chan, Seiji Shirakawa
Summary: Catalytic kinetic resolution is a reliable method for enantioselective synthesis of chiral molecules. However, it is challenging to perform kinetic resolution on racemic compounds with similar substituents at a chiral center. In this study, a kinetic resolution of a-allyl-a-propargyl carboxylic acids was achieved using a chiral bifunctional sulfide catalyst. The utility of the resulting optically active compounds was also demonstrated.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Xiaojian Jiang, Xi Xu, Wei Xu, Pei Yu, Ying-Yeung Yeung
Summary: A catalytic asymmetric halocyclization protocol was developed for the synthesis of benzoxazepinones and benzoxazecinones using (DHQ)(2)PHAL as the catalyst. Excellent yields and enantioselectivities were achieved under mild conditions. The cocrystal structure of the substrate and the catalyst was studied to provide insights into the reaction mechanism.
Article
Chemistry, Organic
Sarah E. Luderer, Behrad Masoudi, Aritra Sarkar, Calvin Grant, Arvind Jaganathan, James E. Jackson, Babak Borhan
Summary: Various structural elements of Cinchona alkaloid dimers were studied to establish a structure-enantioselectivity relationship (SER) in three different halocyclization reactions. The sensitivity of SER to linker rigidity and polarity, alkaloid structure, and the presence of alkaloid side groups defining the catalyst pocket varied in the chlorocyclizations. DFT calculations on methoxylated models revealed high barriers to ether rotation, indicating the importance of conformational rigidity in linker-ether connections.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Yasuyuki Matsushima, Shunsuke Fukuda, Yusuke Kobayashi, Hiroyasu Nezu, Kosuke Nakashima, Shin-ichi Hirashima, Tsuyoshi Miura
Summary: High yields and excellent enantioselectivities (up to 92% ee) of phthalide derivatives were achieved by using a N,N-dibenzyl diaminomethylenemalononitrile organocatalyst in the asymmetric 5-exo bromolactonization of stilbene-type carboxylic acids. This is the first report demonstrating the successful synthesis of highly optically pure phthalide derivatives as the main product using the asymmetric 5-exo bromolactonization of stilbene-type carboxylic acids with various substituents.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Donghui Guo, Jian Wang
Summary: An unprecedented organic catalyzed transamination reaction strategy has been developed for the high-yield synthesis of axial chiral biaryls. This method has a broad substrate applicability and can prepare compounds with potential catalytic applications.
SYNTHESIS-STUTTGART
(2022)
Article
Chemistry, Organic
Kazuki Fujita, Masataka Miura, Yasuhiro Funahashi, Tsubasa Hatanaka, Shuichi Nakamura
Summary: The enantioselective reaction of 2H-azirines with oxazol-S-(4H)-ones using a cinchona alkaloid sulfonamide catalyst has been developed, producing products with consecutive tetrasubstituted stereogenic centers in high yield with high diastereo- and enantioselectivity. The obtained aziridines were converted into various chiral compounds without loss of enantiopurity.
Article
Chemistry, Organic
Dangui Wang, Wentao Zhang, Xunbo Lu, Hongwei Zhou, Fangrui Zhong
Summary: Novel cinchona alkaloid derived iodide catalysts were developed for the enantioselective oxidative alpha-amination of 2-oxindoles, providing various functionalized spiropyrrolidine oxindoles in high yields and with good enantioselectivities. This iodide/ROOH catalytic system features a one-step synthesis of a catalyst with multiple functionalities, ease of operation, and good scalability, thereby enriching the repertoire of iodide catalysis for enantioselective oxidative coupling reactions.
Article
Chemistry, Organic
Ken Okuno, Yasuaki Furuya, Seiji Shirakawa
Summary: The kinetic resolution of racemic compounds is a reliable method to prepare chiral molecules in highly optically enriched forms. However, the kinetic resolution of racemic carboxylic acids has not been well developed. Esterification and lactonization promoted by chiral organocatalysts have been found to be effective methods for the kinetic resolution of chiral carboxylic acids.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Physical
Shuai Wei, Jianing Zhang, Shan Li, Xuebing Ma
Summary: A ship-in-a-bottle strategy was developed for the direct and simple immobilization of 9-amino-(9-deoxy)epi-quinine into hollow polystyrene nano-bowls, achieving good catalytic performance in heterogeneous organocatalysis. The immobilized catalyst displayed fast mass transfer and excellent stability and reusability in acetal hydrolysis/asymmetric aldol tandem reactions. Good to excellent catalytic performances were achieved for acetals bearing electron-withdrawing substituents.
Article
Chemistry, Multidisciplinary
Avene C. Colgan, Rupert S. J. Proctor, David C. Gibson, Padon Chuentragool, Antti S. K. Lahdenpera, Kristaps Ermanis, Robert J. Phipps
Summary: This study reports a significant advancement in the catalytic enantioselective Minisci reaction, allowing the use of α-hydroxy radical coupling partners to obtain valuable enantioenriched secondary alcohol products. The approach is highly regioselective as well as highly enantioselective.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Peter Kisszekelyi, Zsuzsanna Feher, Sandor Nagy, Peter Bagi, Petra Kozma, Zsofia Garadi, Miklos Dekany, Peter Huszthy, Bela Matravolgyi, Jozsef Kupai
Summary: Anchoring cinchona derivatives to trifunctional cores can lead to size-enlarged organocatalysts with varied catalytic activities. The new size-enlarged derivatives showed lower catalytic activities in certain reactions compared to the parent cinchona catalyst, and facilitated catalyst recovery using the PolarClean alternative solvent for nanofiltration-supported applications. Additionally, asymmetric catalysis demonstrated increased selectivity of the catalyst with a bulkier substrate in the Michael reaction.
Article
Biochemistry & Molecular Biology
Aimar Gonzalo-Barquero, Benedicte Lepoittevin, Jacques Rouden, Jerome Baudoux
Summary: A simple and rapid access to fluorinated dithioesters was developed using a one-pot sequence of Grignard reaction-Mitsunobu type substitution. These activated dithioesters exhibited excellent reactivity in aminolysis reactions, allowing the synthesis of various thioamides, including a 4-styrenylthioamide cinchonidine monomer, under environmentally friendly conditions, at room temperature, and in a very short time.
Review
Chemistry, Organic
Tania Xavier, Sylvie Condon, Christophe Pichon, Erwan Le Gall, Marc Presset
Summary: Substituted malonic acid half-oxyesters (SMAHOs) are an original family of malonic acid derivatives that can serve as pro-nucleophiles for greener methodologies through decarboxylative processes. The presence of a substituent on the malonic position offers opportunities for structural diversification. These reagents are well-suited for the development of organocatalyzed processes, and have recently been used for olefination and addition reactions to synthesize elaborated structures under mild conditions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Gregory B. Craven, Dominic P. Affron, Charlotte E. Allen, Stefan Matthies, Joe G. Greener, Rhodri M. L. Morgan, Edward W. Tate, Alan Armstrong, David J. Mann
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2018)
Article
Chemistry, Medicinal
Lindsay E. Evans, Aishwarya Krishna, Yajing Ma, Thomas E. Webb, Dominic C. Marshall, Catherine L. Tooke, James Spencer, Thomas B. Clarke, Alan Armstrong, Andrew M. Edwards
JOURNAL OF MEDICINAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Gregory B. Craven, Dominic P. Affron, Teresa Kosel, Tsz Lam M. Wong, Zoe H. Jukes, Chun-Ting Liu, Rhodri M. L. Morgan, Alan Armstrong, David J. Mann
Article
Chemistry, Organic
Gregory B. Craven, Edward L. Briggs, Charlotte M. Zammit, Alexander McDermott, Stephanie Greed, Dominic P. Affron, Charlotte Leinfellner, Hannah R. Cudmore, Ruth R. Tweedy, Renzo Luisi, James A. Bull, Alan Armstrong
Summary: Vinyl sulfoximines and sulfonimidamides, as S(VI) aza-isosteres of vinyl sulfones and sulfonamides, have been less studied and not yet applied to protein bioconjugation. This study reports various synthetic methodologies for constructing these structures, demonstrating their application in generating fully functionalized probes. Furthermore, a workflow for determining the absolute configuration of enantioenriched vinyl sulfoximines and sulfonimidamides is established.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Lisa Watson, Tanya N. Soliman, Khalil Davis, Joanna Kelly, Nicola Lockwood, Xiaoping Yang, Steven Lynham, John D. Scott, Victoria Crossland, Neil Q. McDonald, David J. Mann, Alan Armstrong, Ulrike Eggert, Peter J. Parker
Summary: The study elucidates the role of PKC-ε in exiting from the abscission checkpoint. Assembly of the 14-3-3 complex and phosphorylation of Aurora B S227 are directly linked to the activity-dependent enrichment of PKC-ε at the midbody, with 14-3-3 association shown to be unnecessary for PKC-ε control.
BIOCHEMICAL JOURNAL
(2021)
Article
Multidisciplinary Sciences
Silvia Martini, Khalil Davis, Rupert Faraway, Lisa Elze, Nicola Lockwood, Andrew Jones, Xiao Xie, Neil Q. McDonald, David J. Mann, Alan Armstrong, Jernej Ule, Peter J. Parker
Summary: PKC epsilon regulates the mitotic events by controlling translation and promoting the assembly of ribonucleoprotein granules containing SERBP1, which is essential for chromosome segregation and successful cell division independent of Aurora B. The authors demonstrate that SERBP1 acts as a parallel mitotic PKC epsilon substrate ensuring the integrity of chromosome segregation and successful cell division.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Bo Qin, Gregory B. Craven, Pengjiao Hou, Julian Chesti, Xinran Lu, Emma S. Child, Rhodri M. L. Morgan, Wenchao Niu, Lina Zhao, Alan Armstrong, David J. Mann, Sheng Cui
Summary: This study successfully applied quantitative irreversible tethering (qIT) to identify fragments that can inhibit the proteases of Enterovirus 71 and SARS-CoV-2, and found that the inhibition could disrupt the active dimeric unit.
ACTA PHARMACEUTICA SINICA B
(2022)
Article
Engineering, Chemical
Mohamad H. Muhieddine, Shekhar K. Viswanath, Alan Armstrong, Amparo Galindo, Claire S. Adjiman
Summary: The pharmaceutical industry needs tools to identify greener and more efficient process routes. This study presents a computer-aided approach based on CAMbD to optimize synthesis and crystallization processes by simultaneously determining optimal solvents, compositions, and process conditions. The proposed methodology utilizes property prediction, simple process models, and optimization to select high-performance solvents. The findings of this approach can guide the selection of solvents for greener pharmaceutical manufacturing.
CHEMICAL ENGINEERING SCIENCE
(2022)
Article
Engineering, Chemical
Lingfeng Gui, Claire S. Adjiman, Amparo Galindo, Fareed Bhasha Sayyed, Stanley P. Kolis, Alan Armstrong
Summary: The combination of chloroformamidinium and diisopropylcarbodiimide has been widely used for amino acid activation, but it can generate unwanted hydrogen cyanide at 20 degrees C, which raises safety concerns. In this study, a computational investigation was conducted to understand the mechanism and kinetics of hydrogen cyanide formation, providing a theoretical basis for developing strategies to suppress its generation.
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
(2023)
Article
Chemistry, Organic
Zhenhao Zhong, Julian Chesti, Alan Armstrong, James A. Bull
Summary: Sulfoximines offer a new approach for improving medicinal chemistry with the addition of other functional groups in sulfonyl compounds. By optimizing conditions, successful synthesis of carbamates with previously low yields, especially those containing pi-functionality, was achieved, including the preparation of propargyl sulfoximine carbamates as potential click handles. Notably, using Rh-2 (esp)(2) as catalyst and a DOE optimization approach led to significantly increased yields.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Computer Science, Interdisciplinary Applications
Lingfeng Gui, Yijun Yu, Titilola O. Oliyide, Eirini Siougkrou, Alan Armstrong, Amparo Galindo, Fareed Bhasha Sayyed, Stanley P. Kolis, Claire S. Adjiman
Summary: Computer-aided molecular design (CAMD) methods are used to generate promising solvents with enhanced reaction kinetics by utilizing a reliable model of solvent effects on reaction rates. In this study, a surrogate model parameterized from computer experiments, specifically quantum-mechanical (QM) data on rate constants, is employed. The selection of solvents for these computer experiments plays a crucial role due to the cost and difficulty of QM calculations. Model-based design of experiments (MBDoE) is used to identify an information-rich solvent set and incorporate it into a QM-CAMD framework. The results of three case studies demonstrate that MBDoE can yield surrogate models with good statistics and identify solvents with enhanced predicted performance in a few iterations and at low computational cost.
COMPUTERS & CHEMICAL ENGINEERING
(2023)
Article
Biochemistry & Molecular Biology
Mostafa Jamshidiha, Thomas Lanyon-Hogg, Charlotte L. Sutherell, Gregory B. Craven, Montse Tersa, Elena De Vita, Delia Brustur, Inmaculada Perez-Dorado, Sarah Hassan, Rita Petracca, Rhodri M. Morgan, Maximo Sanz-Hernandez, Jim C. Norman, Alan Armstrong, David J. Mann, Ernesto Cota, Edward W. Tate
Summary: Rab27A, a small GTPase, plays a significant role in promoting the growth and invasion of multiple cancer types by enhancing secretion of chemokines, metalloproteases, and exosomes. Its flat topology and high affinity for GTP make it a challenging target for inhibition by small molecules. By utilizing unique cysteine residues, covalent ligands for native Rab27A have been identified, providing a platform for developing competitive inhibitors of the Rab27A-effector interaction interface.
RSC MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Aikaterini Diamanti, Zara Ganase, Eliana Grant, Alan Armstrong, Patrick M. Piccione, Anita M. Rea, Jeffery Richardson, Amparo Galindo, Claire S. Adjiman
Summary: By combining experimental probing, detailed kinetic modelling, and quantum-mechanical calculations, this study investigates the mechanism and regioselectivity of a Williamson ether synthesis, revealing significant impact of solvent choice on experimental regioselectivity. Insights into factors affecting regioselectivity and alkylations rates are provided, along with detailed information on reaction kinetics and energy barriers. Quantum-mechanical calculations elucidate structural differences and solvent effects on reaction selectivity.
REACTION CHEMISTRY & ENGINEERING
(2021)
Article
Biology
Gregory B. Craven, Alan Armstrong, David J. Mann
Article
Biochemistry & Molecular Biology
Gregory B. Craven, Dominic P. Affron, Philip N. Raymond, David J. Mann, Alan Armstrong
Article
Chemistry, Organic
Geeta Devi Yadav, Pooja Chaudhary, Balaram Pani, Surendra Singh
Summary: Chiral transition metal complexes with privileged ligands are efficient catalysts for various asymmetric organic transformations. Transition metal complexes of C1-symmetric pyrrolidine-based ligands have been widely used in asymmetric organic reactions. However, a comprehensive review article on the transition metal complexes of chiral C1-symmetric pyrrolidine-based ligands derived from (L)-proline has not been published.
TETRAHEDRON LETTERS
(2024)
