Article
Chemistry, Multidisciplinary
Peng Zhang, Qi Xu, Xiao-Mei Wang, Jia Feng, Chuan-Jun Lu, Yingzi Li, Ren-Rong Liu
Summary: The first enantioselective synthesis of N-N bisindole atropisomers via palladium-catalyzed construction of one indole skeleton is reported in this study. A wide variety of N-N axially chiral bisindoles were generated with good yields and excellent enantioselectivities through a cascade condensation/N-arylation reaction. The reaction mechanism and enantiocontrol were further investigated using density functional theory (DFT) calculations.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Ziqi Zhu, Jieshuai Xiao, Mingjie Li, Zhuangzhi Shi
Summary: This study reports for the first time that chiral nickel complexes can catalyze the intermolecular enantioselective addition of aryl iodides across aldehydes, providing diverse optically active secondary alcohols. The method has a broad substrate scope and mild reaction conditions, avoiding the traditional pre-generation of organometallic reagents.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Zhilong Li, Leitao Huan, Jian Li, Xiaomin Shu, De Zhong, Wenjing Zhang, Haohua Huo
Summary: In this study, an unprecedented enantioselective cross-electrophile coupling (XEC) of α-amino acid derivatives with aryl bromides was achieved using alcohols as reducing agents via Ni/photoredox catalysis. The method utilizes photocatalytically generated α-hydroxyalkyl radicals to convert alkyl electrophiles to alkyl radicals that can selectively couple with aryl bromides. The scalable protocol allows modular access to valuable enantioenriched benzylic amines and can be applied to late-stage diversification with broad functional group tolerance. Mechanistic studies support the versatility of this alcohol-based reactivity for radical generation and subsequent asymmetric cross-coupling. We expect that this alcohol-based cross-coupling will serve as a general platform for the development of appealing yet challenging enantioselective XECs.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Minghui Zhu, Qinglong Zhang, Weiwei Zi
Summary: The study presents a dual-metal catalyzed diastereodivergent coupling method for the synthesis of beta-amino alcohols with multiple stereoisomers, enabling the concise preparation of natural products such as mycestericins F and G.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Linghua Wang, Tao Li, Saima Perveen, Shuai Zhang, Xicheng Wang, Yizhao Ouyang, Pengfei Li
Summary: A nickel-catalyzed general, efficient, and highly enantioselective carboxylation reaction of racemic benzylic (pseudo)halides has been developed, utilizing atmospheric CO2 under mild conditions. A unique chiral 2,2'-bipyridine ligand enabled both high reactivity and stereoselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Peng Zhang, Xiao-Mei Wang, Qi Xu, Chang-Qiu Guo, Peng Wang, Chuan-Jun Lu, Ren-Rong Liu
Summary: In this study, a Pd-catalyzed cross-coupling strategy was employed for the synthesis of N-C axially chiral biaryl molecules with excellent enantioselectivities and good yields. The practicality of this reaction was demonstrated in the synthesis of biologically relevant molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Wang Yao, Chuan-Jun Lu, Li-Wen Zhan, Yi Wu, Jia Feng, Ren-Rong Liu
Summary: In this study, a palladium-catalyzed enantioselective C-H activation method for pyrroles was reported, which successfully synthesized structurally diverse indole-pyrrole atropisomers with a chiral N-N axis, showing high yields and enantioselectivities. Furthermore, the kinetic resolution of trisubstituted N-N heterobiaryls with more sterically demanding substituents was also achieved. This versatile method enables the rapid and selective functionalization of pyrroles, facilitating the synthesis of valuable and complex N-N atropisomers.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Shuai Zhang, Saima Perveen, Yizhao Ouyang, Liang Xu, Tao Yu, Min Zhao, Linghua Wang, Peidong Song, Pengfei Li
Summary: A new class of chiral bipyridine ligands, SBpy, featuring minimized steric hindrance and structural tunability, was designed and developed for the highly enantioselective Ni-catalyzed addition reaction. Compared to known methods, this reaction is more cost-effective and tolerant towards functional groups. The proposed reaction mechanism and stereocontrol model were based on experimental and computational results.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Saima Perveen, Shuai Zhang, Linghua Wang, Peidong Song, Yizhao Ouyang, Jiao Jiao, Xin-Hua Duan, Pengfei Li
Summary: The first nickel-catalyzed highly enantioselective reductive Ullmann coupling of ortho-chlorinated aryl aldehyde was achieved under mild reaction conditions using a chiral 2,2'-bipyridine ligand (+)-DTB-SBpy, resulting in the synthesis of axially chiral biphenyl or binaphthyl dials with high yields and enantioselectivities. The versatility of the products as common synthetic intermediates for diverse axially chiral ligands, catalysts, and functional molecules was demonstrated through short-step transformations. Additionally, this protocol enabled the concise and highly enantioselective formal total synthesis of biologically active natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Physical
You-Dong Shao, Dao-Juan Cheng
Summary: Chiral phosphoric acid catalysis has witnessed significant development in the past two decades, with successful attempts in synthesizing enantioenriched axially chiral compounds through various strategies. This review highlights the advances in atropisomeric heterocycles construction enabled by chiral phosphoric acid catalysis, aiming to motivate continuous interest in atroposelective reactions.
Article
Chemistry, Multidisciplinary
Cong Fu, Qi Xiong, Lu Xiao, Ling He, Tian Bai, Zongpeng Zhang, Xiu-Qin Dong, Chun-Jiang Wang
Summary: This article proposes a novel approach to the stereodivergent synthesis of carbocyclic alpha-quaternary amino acid derivatives through sequential dual Cu/Ir-catalyzed asymmetric allylation and ring-closing metathesis. The method exhibits high yields, exclusive regioselectivities, and excellent diastereoselectivities and enantioselectivities. Furthermore, it is capable of synthesizing challenging seven and eight-membered carbocyclic alpha-amino acid derivatives.
CHINESE JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Jiajing Li, Bing Yu, Zhan Lu
Summary: Imidazoline, as a structural analog of oxazoline, has gained significant attention in the rational design of chiral ligands due to its additional N-substituent allowing for fine-tuning of electronic and steric effects. Various chiral imidazoline ligands have been designed and employed in asymmetric organic reactions, expanding the applications of chiral synthesis.
CHINESE JOURNAL OF CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Rosa Lopez, Claudio Palomo
Summary: This Minireview highlights the limited but significant catalytic methods for the generation of planar chirality in strained molecules, and serves as an inspiration for the development of new unconventional procedures in the future.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Li-Wen Zhan, Chuan-Jun Lu, Jia Feng, Ren-Rong Liu
Summary: This study reports for the first time that palladium compounds can catalyze the hydroarylation of 1-alkynylindoles with organoborons, resulting in the synthesis of chiral C-N atropisomers. The reaction conditions are mild and lead to excellent regio-, stereo- (Z-selectivity), and enantioselectivity. The simplicity, high stereoselectivity, and good functional group tolerance of this catalytic system make it highly attractive.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Eliezer Ortiz, Brian J. Spinello, Yoon Cho, Jessica Wu, Michael J. Krische
Summary: Iodide-bound ruthenium-JOSIPHOS complexes catalyze the redox-neutral C-C coupling of primary alcohols with methylallene or 1,3-butadiene to form anti-crotylation products with high levels of diastereo- and enantioselectivity. This method allows for direct crotylation of primary alcohols in the presence of unprotected secondary alcohols, significantly reducing the number of steps required to synthesize substructures of spirastrellolide B and leucascandrolide A.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Nikoletta Harsagi, Reka Henyecz, Peter Abranyi-Balogh, Laszlo Drahos, Gyorgy Keglevich
Summary: Investigations have shown that a series of alkylphoshonic acids can undergo monoesterification with C-2-C-4 alcohols under microwave irradiation in the presence of [bmim][BF4], showing high selectivity and reasonable isolated yields. DFT calculations explored a three-step mechanism, indicating that the high enthalpy of activation can only be overcome by MW irradiation, with [bmim][BF4] enhancing the absorption of MW energy.
Review
Pharmacology & Pharmacy
Nikolett Peczka, Zoltan Orgovan, Peter Abranyi-Balogh, Gyorgy Miklos Keseru
Summary: This review provides an overview of electrophilic warheads used for protein labeling in chemical biology and medicinal chemistry. The warheads are discussed based on targeted residues, mechanism, and selectivity, and analyzed using multiple datasets. Despite the availability of numerous electrophilic warheads, only a fraction of them are used in current drug discovery projects. Recent studies have identified new tractable residues, but the discovery of new warheads for these residues is still needed.
EXPERT OPINION ON DRUG DISCOVERY
(2022)
Article
Chemistry, Organic
Gyorgyi Kovanyi-Lax, Csilla Hargitai, Peter Abranyi-Balogh, Tamas Nagy, Gabor Toth, Zsofia Garadi, Gabor Nemeth, Angela Pandur, Simon Horvath, Andras Dancso, Gyula Simig, Balazs Volk
Summary: In this study, the reactions of ortho-(pivaloylaminomethyl)benzaldehydes using boron trifluoride diethyl etherate (BF3 center dot OEt2) as the catalyst were described, and the formation of a new dimer-like keto compound and an oxoindene-type by-product was observed. Detailed characterization and theoretical calculations support the proposed mechanisms and explain the product distribution.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Inorganic & Nuclear
Nikoletta Harsagi, Nora Zsuzsa Kiss, Peter Abranyi-Balogh, Gyorgy Keglevich
Summary: The preparation of dialkyl phenylphosphonates was evaluated through oxidation of phenyl-H-phosphinates and MW-assisted direct esterification of phenylphosphonic acid. The esterification reactions were carried out under MW irradiation in the presence of an ionic liquid as the catalyst.
PHOSPHORUS SULFUR AND SILICON AND THE RELATED ELEMENTS
(2022)
Article
Chemistry, Medicinal
Laszlo Petri, Peter Abranyi-Balogh, Darius Vagrys, Timea Imre, Nikolett Varro, Istvan Mandity, Anita Racz, Lucia Wittner, Kinga Toth, Estilla Zsofia Toth, Tunde Juhasz, Ben Davis, Gyoergy Miklos Keseru
Summary: In this study, a covalent design strategy targeting intrinsically disordered proteins (IDPs) was developed based on the promising results of targeted covalent inhibitors (TCIs) on challenging targets. Using tau protein as a model system, suitable warheads were introduced to non-covalent scaffolds of potential tau aggregation inhibitors. The designed covalent tau binders effectively inhibited tau aggregation in aggregation models, providing promising candidates for the treatment of tauopathies.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Peter Abranyi-Balogh, Nikoletta Harsagi, Laszlo Drahos, Gyorgy Keglevich
Summary: The MW-assisted direct esterification of certain P-acids is a green method. Quantum chemical calculations revealed the activation enthalpies for the conversion of monoalkylphosphate to dialkylphosphate and dialkylphosphate to trialkylphosphate. The direct monoesterification can be performed with MW irradiation in the presence of a suitable ionic liquid additive, while the less favorable energetics of the second step requires another method for conversion to triesters.
Article
Chemistry, Medicinal
Katarina Grabrijan, Martina Hrast, Matic Proj, Ana Dolsak, Irena Zdovc, Timea Imre, Laszlo Petri, Peter Abranyi-Balogh, Gyorgy M. Keseru, Stanislav Gobec
Summary: The study focused on the development of new antibacterial agents by inhibiting the enzyme MurA. A potent compound with potential antibacterial activity was identified, providing a valuable starting point for the development of new antibiotics.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Peter Abranyi-Balogh, Aaron Keeley, Gyorgy G. Ferenczy, Laszlo Petri, Timea Imre, Katarina Grabrijan, Martina Hrast, Damijan Knez, Janez Ilas, Stanislav Gobec, Gyorgy M. Keseru
Summary: The second generation of heterocyclic electrophiles, the quaternized analogue of the heterocyclic covalent fragment library, showed improved reactivity and MurA inhibitory potency. Quantum chemical reaction barrier calculations, GSH reactivity assay, and thrombin counter screen were used to explain the improved reactivity and selectivity of the N-methylated heterocycles and compare the two generations of heterocyclic electrophiles.
Article
Chemistry, Medicinal
Zoltan Orgovan, Nikolett Peczka, Laszlo Petri, Peter Abranyi-Balogh, Ivan Randelovic, Szilard Toth, Gergely Szakacs, Kinga Nyiri, Beata Vertessy, Gyula Palfy, Istvan Vida, Andras Perczel, Jozsef Tovari, Gyorgy M. Keseru
Summary: Covalent fragment screening of a diverse library of non-covalent scaffolds equipped with 40 different electrophilic functionalities identified two potential inhibitor chemotypes targeting the G12C mutant KRas. These scaffolds showed promising results in in vitro cellular and in vivo xenograft models, demonstrating their potential as starting points for covalent drug discovery programs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Laszlo Petri, Peter Aabranyi-Balogh, Noemi Csorba, Aaron Keeley, Jozsef Simon, Ivan Randelovic, Jozsef Tovari, Gitta Schlosser, Daniel Szabo, Laszlo Drahos, Gyoergy M. Keseru
Summary: SuFEx chemistry is based on the unique reactivity of the sulfonyl fluoride group with a range of nucleophiles. Sulfonyl fluorides can label multiple nucleophilic amino acid residues, making them popular in both chemical biology and medicinal chemistry applications. In this study, a small sulfonyl fluoride library was synthesized and characterized, resulting in the identification of a 3-carboxybenzenesulfonyl fluoride warhead for tagging nucleophilic residues. Coupling diverse fragments to this warhead could yield a library of sulfonyl fluoride bits (SuFBits) for screening against protein targets, facilitated by mass spectrometry identification of weak fragments.
Article
Chemistry, Multidisciplinary
Denes Szepesi Kovacs, Balazs Chiovini, Dalma Muller, Estilla Zsofia Toth, Anna Fulop, Peter Abranyi-Balogh, Lucia Wittner, Gyorgy Varady, Odon Farkas, Gabor Turczel, Gergely Katona, Balazs Gyorffy, Gyorgy Miklos Keseru, Zoltan Mucsi, Balazs J. Rozsa, Ervin Kovacs
Summary: A novel family of julolidine-containing fluorescent rhodolsequipped with a wide variety of substituents was synthesized using a versatile two-step process. The synthesized compounds were fully characterized and demonstrated excellent fluorescence properties for microscopy imaging. The best candidate was conjugated to the therapeutic antibody trastuzumab through a copper-free strain-promoted azide-alkyne click reaction. The rhodol-labeled antibody was successfully used for in vitro confocal and two-photon microscopy imaging of Her2+ cells.
Article
Chemistry, Organic
Denes Szepesi Kovacs, Bence Kontra, Balazs Chiovini, Dalma Muller, Estilla Zsofia Toth, Peter Abranyi-Balogh, Lucia Wittner, Gyoergy Varady, Gabor Turczel, Odon Farkas, Michael C. Owen, Gergely Katona, Balazs Gyorffy, Gyorgy Miklos Keseru, Zoltan Mucsi, Balazs J. Rozsa, Ervin Kovacs
Summary: An asymmetric cyanine-type fluorescent dye was designed and synthesized with excellent fluorescence properties for confocal microscopy. A cyanine-labeled antibody was successfully constructed and applied for in vitro imaging and flow cytometry.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Andras Gy. Nemeth, Renata Szabo, Krisztina Nemeth, Gyorgy M. Keseru, Peter Abranyi-Balogh
Summary: This study discovered the reactivity of easily accessible electron deficient alkenes towards sulfur and developed a new pseudo-multicomponent reaction for the preparation of polysulfides.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
D. Knez, M. Hrast, I. Sosic, P. Abranyi-Balogh, M. Proj, L. Petri, L. G. Iacovino, C. Binda, G. M. Keseru, S. Gobec
Article
Chemistry, Multidisciplinary
Denes Szepesi Kovacs, Imre Hajdu, Gergely Meszaros, Lucia Wittner, Domokos Meszena, Estilla Zsofia Toth, Zita Hegedus, Ivan Randelovic, Jozsef Tovari, Timea Szabo, Bence Szilagyi, Matyas Milen, Gyorgy Miklos Keseru, Peter Abranyi-Balogh
Summary: The first representatives of a new fluorescent boro-beta-carboline family were synthesized by inserting difluoroboranyl group into oxaza or diaza core, exhibiting good photophysical properties with fine Stokes-shifts. Quantum chemical computations suggested improved properties of diazaborinino-carbolines over oxazaborolo-carbolines. This chemotype was nominated as a new fluorophore for developing fluorescent probes.
