Article
Chemistry, Multidisciplinary
Daniel Rozsar, Alistair J. M. Farley, Iain McLauchlan, Benjamin D. A. Shennan, Ken Yamazaki, Darren J. Dixon
Summary: This article describes the enantioselective intermolecular conjugate addition of nitroalkanes to unactivated alpha,beta-unsaturated esters catalyzed by a bifunctional iminophosphorane (BIMP) superbase. It provides a straightforward approach to the synthesis of pharmaceutically relevant enantioenriched gamma-nitroesters with unprecedented selectivity. The methodology demonstrates broad substrate scope and has been successfully applied on a gram scale with reduced catalyst loading, allowing for catalyst recovery.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Won Jun Jang, Jeongkyu Woo, Jaesook Yun
Summary: The study reported a method to synthesize enantioenriched alkylboron compounds through conjugate addition, which are influenced by two contiguous carbon stereogenic centers, with high yield and enantioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Ming Cui, Zhi-Yuan Zhao, Martin Oestreich
Summary: Chiral bis(phosphine) monooxides derived from C-2-symmetric bis(phosphines) have been found to exhibit superior enantioselection in copper-catalyzed conjugate borylation and 1,6-addition reactions. Specifically, (R,R)-Bozphos ligand shows significantly higher enantiomeric excesses and chemical yields compared to parent (R,R)-Me-Duphos ligand.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Hu Tian, Hong-Ming Zhang, Liang Yin
Summary: In this article, a copper(I)-catalyzed asymmetric conjugate addition/protonation with selenols and alpha-substituted alpha,beta-unsaturated thioamides is described, which produces a series of chiral selenides with high to excellent enantioselectivity. The reaction shows a broad substrate scope for both selenols and alpha-substituted alpha,beta-unsaturated thioamides. The catalytic system is also successfully used for asymmetric selenation of beta-substituted alpha,beta-unsaturated thioamides. A [Cu-(R,R-P)-TANIAPHOS]-SePh species is identified by Se-77 NMR spectra, with a chemical shift at delta 462 ppm. Furthermore, a {[Cu-(R)-TOL-BINAP]-SePh}(2) species is characterized by X-ray analysis, confirming the formation of Cu-Se bond in the reaction. Finally, the straightforward transformations of the thioamide group to amine and thioester are demonstrated.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Applied
Deyuan Meng, Jing He, Woojin Yoon, Hoseop Yun, Jung Tae Han, Jaesook Yun
Summary: In this study, the catalytic 1,6-addition of chiral alkyl copper nucleophiles generated from borylalkenes and a copper-hydride catalyst was successfully conducted under mild conditions. The controlled chemo- and stereoselectivity played a crucial role in the reductive coupling process, resulting in efficient synthesis of asymmetric 1,6-adducts of p-quinone methides through multicomponent and catalytic tandem reactions.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Review
Chemistry, Inorganic & Nuclear
Xing -Bang Liu, Yuan Huang
Summary: In this review, recent advances in the formation of C-C and C-X bonds using synergistic Ni/Cu catalytic systems are summarized. The review includes various reactions such as Sonogashira-type reactions, asymmetric allylic/propargylic alkylations, hydrofunctionalizations, silylations, borylations, Suzuki-type reactions, C-H bond functionalization, Nazarov cyclization, and diarylation of unreactive alkenes. The unique advantages of the Ni/Cu catalyst system are discussed, and its potential applications in organic synthesis, medicinal chemistry, and materials science are highlighted.
COORDINATION CHEMISTRY REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
Brian S. Daniels, Xintong Hou, Stephanie A. Corio, Lindsey M. Weissman, Vy M. Dong, Jennifer S. Hirschi, Shaozhen Nie
Summary: A copper catalyst is reported for the addition of phosphines to cyclopropenes at ambient temperature. Various cyclopropylphosphines with different steric and electronic properties can now be synthesized in high yields and enantioselectivities. Through a combined experimental and theoretical study, the mechanism is proposed to involve insertion of a Cu-I-phosphido into a carbon-carbon double bond.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Physical
Thomas M. Horsley Downie, Mary F. Mahon, John P. Lowe, Rowan M. Bailey, David J. Liptrot
Summary: The reaction of phosphorus(III) esters with pinacolborane using an NHC-copper(I) catalyst allows for the quick generation of various phosphines, which can be further used in the synthesis of different phosphorus-containing compounds. This telescoped approach provides access to a range of P-H bonded species with high conversions, enabling the synthesis of diverse phosphorus-based molecules without the need to handle toxic compounds.
Article
Chemistry, Physical
Junwen Wang, Jun Li, Yan Wang, Sisi He, Hengzhi You, Fen -Er Chen
Summary: In this study, a polymer-supported chiral heterogeneous copper catalyst was reported, which demonstrated high reactivity and enantioselectivity in asymmetric conjugate addition reactions.
Article
Chemistry, Multidisciplinary
Yu-Chao Wang, Zhao-Xin Xiao, Miao Wang, Shao-Qian Yang, Jin-Biao Liu, Zhi-Tao He
Summary: This study presents modular protocols for 1,5-conjugate addition reactions via palladium hydride catalysis, which has been considered unfeasible. The results show that the 1,5-conjugate addition products can be conveniently transformed into various privileged enantioenriched motifs, indicating the potential applications of this method in synthesis.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Yan-Bo Li, Hu Tian, Shuai Zhang, Jun-Zhao Xiao, Liang Yin
Summary: In this study, a copper(I)-catalyzed reaction of diarylphosphines and O-benzoyl hydroxylamines was developed, leading to the synthesis of aminophosphinites and P-chiral aminophosphinites. The reaction mechanism was proposed and further transformation to P-chiral phosphines was achieved.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Inorganic & Nuclear
Jessica Margalef, Maria Biosca, Pol de la Cruz Sanchez, Jorge Faiges, Oscar Pamies, Montserrat Dieguez
Summary: The success of phosphine-oxazoline ligands has led to advancements in P-oxazoline ligand families, resulting in diverse structures and more efficient ligands for asymmetric transformations. Through proper design, these heterodonor bidentate ligand families exhibit superior catalytic performance in a variety of asymmetric reactions.
COORDINATION CHEMISTRY REVIEWS
(2021)
Article
Chemistry, Applied
Brigita Mudrakova, Peter Kisszekelyi, Denisa Vargova, Dorota Zakiewicz, Radovan Sebesta
Summary: This paper presents a highly enantio- and diastereoselective tandem transformation method, using Cu-catalyzed conjugate addition of Grignard reagents to heterocyclic Michael acceptors, followed by one-pot trapping of in situ formed enolates with stabilized carbocations or their equivalents. This method allows the installation of structurally attractive substituents on heterocyclic compounds.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Multidisciplinary
Barry M. Trost, Guoting Zhang, Minghao Xu, Xiaotian Qi
Summary: A new bifunctional ligand with chiral NHC and prolinol moieties was introduced for asymmetric allylic alkylation reactions. The designed ligand facilitated the formation of various gamma-vinyl ketones with good regio- and enantio-selectivity using an in situ formed Cu/Zn hetero-bimetallic complex. Computational studies supported the role of ligand-substrate steric interactions in determining the stereoselective outcome.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Reina Nonami, Yusei Morimoto, Kazuya Kanemoto, Yasunori Yamamoto, Tomohiko Shirai
Summary: We report an unprecedented catalytic protocol for the enantioselective decarbonylative transformation of aryl aldehydes. This asymmetric C-C bond formation is achieved through the decarbonylation of aldehydes catalyzed by chiral iridium complexes and the formation of an aryl-iridium intermediate. The reaction shows broad functional group compatibility and generates no waste apart from carbon monoxide.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Andreas Stein, Persefoni Hilken Nee Thomopoulou, Corazon Frias, Sina M. Hopff, Paloma Varela, Nicola Wilke, Arul Mariappan, Jorg-Martin Neudoerfl, Alexey Yu Fedorov, Jay Gopalakrishnan, Benoit Gigant, Aram Prokop, Hans-Gunther Schmalz
Summary: The synthesis and investigation of PT-100, a potential anticancer drug, were reported. PT-100 exhibited high antiproliferative and apoptosis-inducing effects, especially in multidrug-resistant cancer cell lines, and showed synergistic effects with vincristine in certain cell lines.
Article
Biochemistry & Molecular Biology
Pascal M. Engelhardt, Sebastian Florez-Rueda, Marco Drexelius, Joerg-Martin Neudoerfl, Daniel Lauster, Christian P. R. Hackenberger, Ronald Kuehne, Ines Neundorf, Hans-Guenther Schmalz
Summary: Researchers used a rigidified diproline-derived module ProM-5 to induce alpha helicity in ACE2-inspired peptide sequences. They found increased alpha helicity when non-binding amino acids were replaced with alanine. The binding affinities of the peptides towards the spike protein showed that the alpha-helical content had only a subtle influence, with one specific peptide displaying a strong binding affinity.
Article
Chemistry, Multidisciplinary
Lars Hemmersbach, Yannick Schreiner, Xinmiao Zhang, Finn Dicke, Leon Hunemeyer, Jorg-Martin Neudorfl, Thomas Fleming, Benito Yard, Hans-Gunther Schmalz
Summary: Due to the beneficial effects of carbon monoxide, CO-releasing molecules show promising potential applications in medicine. In this study, mitochondria-targeting CO-releasing molecules were synthesized and their biological activity, anti-inflammatory effects, and cellular energy metabolism were investigated.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Irene Reimche, Haiqian Yu, Ni Putu Ariantari, Zhen Liu, Kay Merkens, Stella Rotfuss, Karin Peter, Ute Jungwirth, Nadine Bauer, Friedemann Kiefer, Joerg-Martin Neudoerfl, Hans-Guenther Schmalz, Peter Proksch, Nicole Teusch
Summary: The study shows that phenanthroindolizidine alkaloids (PAs) can effectively block nuclear factor kappa B (NF kappa B), thus having the potential to combat triple-negative breast cancer (TNBC). Additionally, PAs demonstrate better therapeutic effects against TNBC compared to the gold standard drug paclitaxel.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Inorganic & Nuclear
Anna Schlundt nee Goederz, Lars Hemmersbach, Steffen Romanski, Joerg-Martin Neudoerfl, Hans-Guenther Schmalz
Summary: In this research, we investigated the use of enzyme-triggered CO-releasing molecules (ET-CORMs). We were interested in modifying 2-acetoxy-5-azido-1,3-cyclohexadiene-Fe(CO)3 (rac-2) using Cu-catalyzed azide-alkyne cycloaddition (CuAAC click chemistry). Surprisingly, the treatment of [2-acetoxy-cyclohexadienyl-Fe(CO)3]+[PF6]- with certain azide compounds resulted in the formation of 2-acetoxy-1-azido-2,4-cyclohexadiene-Fe(CO)3 (rac-9) as the main product. We discovered that rac-2 is primarily formed under kinetic control and undergoes a rapid isomerization to rac-9, a thermodynamic product, through a vinylogous Winstein rearrangement mechanism. We also found that rac-9 can act as an enzyme-triggered CO-releasing molecule (ET-CORM) in the presence of porcine liver esterase.
Article
Chemistry, Organic
Joss Pepe Strache, Lukas Muenzer, Andreas Adler, Dirk Blunk, Hans-Guenther Schmalz
Summary: We investigated the enantioselective Ni-catalyzed hydrocyanation of 1,3-diarylpropenes. A series of (E)-homostilbenes were prepared by Pd-catalyzed coupling, and the hydrocyanation of various homostilbenes was studied using a Ni(cod)2/TADDOL-derived chiral phosphine-phosphite ligand catalyst system. The methodology was applied in a short synthesis of a colchicine analogue, and the absolute configuration of 2,4-diphenylbutyronitrile was determined by comparing experimental and calculated ECD spectra.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Lars Hemmersbach, Ruth Adam, Christina Plevnali, Xinmiao Zhang, Benito Yard, Hans-Gunther Schmalz
Summary: A new anti-inflammatory agent, which releases carbon monoxide (CO) and a specialized pro-resolving mediator, was successfully synthesized. It can induce HO-1 expression in endothelial cells and M2 polarized macrophages, but its role in inflammation resolution still needs to be assessed.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Lea Hartmann, Florian P. Seebeck, Hans-Guenther Schmalz, Dirk Gruendemann
Summary: Recently, a non-enzymatic multi-step cycle for the regeneration of ergothioneine (ET) has been discovered after reaction with singlet oxygen (1O2) by glutathione (GSH). Through experiments using labeled ET and high resolution mass spectrometry analysis, the reaction scheme has been revised and extended, with 1O2 attacking the imidazole ring and the sulfur of ET. The reduction of the hydroperoxide intermediates and the sulfine allows for the complete regeneration of ET by GSH, without the need for enzyme involvement.
FREE RADICAL BIOLOGY AND MEDICINE
(2023)
Article
Chemistry, Organic
Lars Hemmersbach, Hans-Guenther Schmalz
Summary: This paper presents a short and efficient synthetic access to functionalized compounds with major structural elements of the natural product populusone. By utilizing a diastereoselective Mukaiyama aldol addition and a triflic anhydride-induced oxa-Michael addition, the sensitive 2-oxa-bicyclo[2.2.2]octene unit is constructed and directly used in a subsequent Suzuki cross-coupling. Although attempts to close the strained 10-membered ring were not successful, the developed synthetic scheme allows the rapid synthesis of advanced intermediates, which may lead to the total synthesis of populusone in the future.
Article
Chemistry, Multidisciplinary
Reinhold Gregor Wuestenberg, Joerg-Martin Neudoerfl, Hans-Guenther Schmalz
Summary: Using the marine natural product ptilocaulin as a starting point, the study investigated the supramolecular behavior of N,N'-bridged guanidinium nitrates in crystalline state. Various N,N'-bridged guanidines were synthesized and converted into nitrate salts, and their crystal structures were determined. The study identified several recurring supramolecular motifs formed by charge-assisted self-assembly and revealed the value of N,N'-bridged guanidines as building blocks for supramolecular chemistry and crystal engineering.
ISRAEL JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Organic
Lukas Muenzer, Hans-Guenther Schmalz
Summary: In this paper, the results and experience gained from 20 years of research in the field of polyketidic natural products with a tetra-ortho-substituted benzophenone substructure are summarized. Despite the challenges posed by the intense interactions of the functional groups adjacent to the ketone bridge, the synthesis of such systems is important for understanding the non-enzymatic formation of related compounds in Nature. Successes, failures, and surprising reactivities are reported based on the approaches used to target Mumbaistatin and Pestalone, both of which are of high biological relevance.
Article
Chemistry, Organic
Dominik Albat, Slim Chiha, Stephan Dohmen, Pascal M. Engelhardt, Hanna Sebode, Arne Soicke, Matthias Barone, Matthias Mueller, Ronald Kuehne, Hans-Guenther Schmalz
Summary: In this study, we describe the modular assembly of ProM-based pentapeptidic EVH1 ligands through liquid phase peptide synthesis, which allows for facile alteration of the C-terminal ProM unit and improved overall yields and purity.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Iuliia A. A. Gracheva, Hans-Gunther Schmalz, Elena V. V. Svirshchevskaya, Ekaterina S. S. Shchegravina, Alexey Yu. Fedorov
Summary: We developed a four-step semisynthetic approach to obtain a highly versatile allocolchicine-related chiral aryne intermediate from natural colchicine. The generated benzyne intermediate produced a range of non-racemic heterocyclic allocolchicinoids, which exhibited potent cytotoxicity against COLO 357, OSA, and Raji cells. This methodology is attractive for the synthesis of new libraries of cytotoxic tubulin inhibitors.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Chuanke Chong, Le Chang, Isabelle Grimm, Qunlong Zhang, Yang Kuang, Bingjian Wang, Jingyi Kang, Wenhui Liu, Julian Baars, Yuanqiang Guo, Hans-Guenther Schmalz, Zhaoyong Lu
Summary: We present a concise and diverse synthetic strategy for the revised structures of marine anti-cancer sesquiterpene hydroquinone meroterpenoids (+)-dysiherbols A-E (6-10). The total synthesis was accomplished using dimethyl predysiherbol 14 as a key intermediate. Two different improved syntheses of dimethyl predysiherbol 14 were developed, and two different approaches were used to construct the core ring system. The total synthesis of (+)-dysiherbols A-E (6-10) was achieved by starting from dimethyl predysiherbol 14, leading to the revision of their originally proposed structures.
Article
Chemistry, Organic
Marco T. Klein, Bernhard M. Krause, Jorg-Martin Neudorfl, Ronald Kuhne, Hans-Gunther Schmalz
Summary: A synthesis method for the new tetracyclic scaffold ProM-19 involves preparing key building blocks through specific reactions and synthesizing the target compound. This synthesis method was also applied for the preparation of a potential ligand.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)