Review
Chemistry, Organic
Maciej Majdecki, Patryk Niedbala, Agata Tyszka-Gumkowska, Janusz Jurczak
Summary: This short review focuses on asymmetric phase-transfer reactions using hybrid ammonium Cinchona catalysts with hydrogen-bond donor groups. The emphasis is on the advantages of additional functional groups present in the catalyst structure.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Organic
Bedrich Formanek, Vit Seferna, Marta Meazza, Ramon Rios, Mahendra Patil, Jan Vesely
Summary: This study reports the organocatalytic amination of pyrazol-5-ones with azodicarboxylates catalyzed by quinine, yielding enantiomerically enriched hydrazine adducts with quaternary stereocenters in high yields and enantioselectivities. Theoretical calculations help propose the relationship between the quinine catalyst and reactants, explaining the observed stereochemical outcome and trends in reaction effectiveness.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Patryk Niedbala, Maciej Majdecki, Piotr Grodek, Janusz Jurczak
Summary: This work describes the development of a highly optimized method for generating quaternary stereogenic centers in beta-keto esters. The method utilizes a phase-transfer alkylation reaction catalyzed by hybrid Cinchona catalysts, resulting in efficient generation of optically active products with excellent enantioselectivity using only 1 mol% catalyst.
Article
Chemistry, Applied
Luka Ciber, Sebastijan Ricko, Jure Gregorc, Franc Pozgan, Jurij Svete, Helena Brodnik, Bogdan Stefane, Uros Groselj
Summary: This study demonstrates that Arylidene-Delta(2)-pyrrolin-4-ones can undergo organocatalyzed annulation with malononitrile to form dihydropyrano[3,2-b]pyrroles. The enantiomeric excess of the products can be increased by trituration. The enantioselectivity depends on the nature of the substrate and the conformation of the catalyst, which is solvent-controlled. The reaction mechanism involves a Michael addition reaction step followed by 6-exo-dig annulation, and the rate determining step is the former, consistent with the proposed model.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
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
Yakun Wang, Shuaifei Wang, Yufeng Wu, Ting Zhao, Jie Liu, Junlin Zheng, Lin Wang, Jieli Lv, Tao Zhang
Summary: We have developed a highly efficient enantioselective fluorination reaction of 4-substituted pyrazolones using amide-based Cinchona alkaloids catalysts. The reaction affords tetrasubstituted fluorine-attached chiral center products in high yields (up to 99%) and excellent enantioselectivities (up to 98% ee). Our method features low catalyst loading, short reaction times, and wide substrate scope. Furthermore, the reaction can be carried out under sustainable conditions for 10 cycles, and the optically pure product (>99.5% ee) can be easily obtained on a multigram scale through simple extraction and recrystallization. Controlled experiments and DFT studies revealed that the multiple hydrogen bonding interactions and steric hindrance contribute to the high enantioselectivity and reactivity. This transformation provides a practical method for the preparation of chiral fluorine-containing compounds with a simple operational protocol and low catalyst loading.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Applied
Laura Carceller-Ferrer, Gonzalo Blay, M. Carmen Munoz, Jose R. Pedro, Carlos Vila
Summary: A diastereo- and enantioselective synthesis of spirocyclopropylpyrazolones was achieved through a Michael/alkylation cascade reaction of 4-arylidenepyrazol-5-ones with diethyl 2-bromomalonate catalyzed by (DHQ)(2)AQN. The corresponding spirocyclic compounds were obtained selectively with yields of 30-83%, diastereoselectivities ranging from 60:40 to >95:5, and enantiomeric excess of 26-93% under mild reaction conditions.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Organic
Lotte Stockhammer, Johannes Schoergenhumer, Christopher Mairhofer, Mario Waser
Summary: This study introduces an unprecedented strategy for the asymmetric alpha-chlorination of beta-keto esters using simple Cinchona alkaloid catalysts and hypervalent iodine-based Cl-transfer reagents. The Cinchona species was found to act as a nucleophilic catalyst, generating a chiral electrophilic Cl-transfer reagent in situ, leading to good yields and enantioselectivities under operationally simple conditions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Yuk-Cheung Chan, Xinyan Wang, Ying-Pong Lam, Jonathan Wong, Ying-Lung Steve Tse, Ying-Yeung Yeung
Summary: A catalyst-controlled enantiodivergent bromolactonization of olefinic acids has been developed by using different quinine-derived amino-amides as catalysts. Switching the position of the methoxy substituent in the aryl amide system alters the asymmetric induction, leading to the desired lactone with good enantioselectivity and yield. Mechanistic studies reveal that the differences in steric and electronic effects of the catalyst substituent affect the reaction mechanism.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Biochemistry & Molecular Biology
Mariola Zielinska-Blajet, Zaneta A. Mala, Rafal Kowalczyk
Summary: Novel chiral Cinchona-alkaloid based selenoureas were developed by varying the steric and electronic surroundings of the hydrogen-bonding motif, showing high efficiency in catalyzing Michael reactions and achieving chiral products with high enantioselectivity. The asymmetric Michael-hemiacetalization reaction of benzylidene pyruvate and dimedone, catalyzed by selenoureas, resulted in good yields and high enantioselectivity. The efficacy of the new hydrogen-bond donors was further confirmed in solvent-free reactions under ball mill conditions, supporting the sustainability of the devised catalytic protocol.
Article
Chemistry, Organic
Francesco Trenti, Kotaro Yamamoto, Benke Hong, Christian Paetz, Yoko Nakamura, Sarah E. O'Connor
Summary: Transcriptomic data led to the discovery of three enzymes involved in the biosynthesis of quinine, with a medium-chain alcohol dehydrogenase and an esterase being key in producing the biosynthetic intermediate dihydrocorynantheal from strictosidine aglycone. Additionally, the specific O-methyltransferase for 6'-hydroxycinchoninone suggested the final step order to be cinchoninone hydroxylation, methylation, and keto-reduction.
Editorial Material
Chemistry, Organic
Nimisha Bania, Dipankar Barman, Subhas Chandra Pan
Summary: An organocatalytic asymmetric oxa-Michael-Michael reaction was developed for the synthesis of spirotetrahydropyranopyrazolones. By utilizing a quinine-derived squaramide catalyst, the reaction achieved moderate yields, excellent diastereomeric ratios, and high to excellent enantioselectivities under mild reaction conditions.
Article
Chemistry, Multidisciplinary
Martin Berger, Davide Carboni, Paolo Melchiorre
Summary: The study presents the first catalytic enantioselective conjugate addition of allyl groups to alpha, beta-unsaturated aldehydes, utilizing the visible-light-excitation of chiral iminium ions to activate allyl silanes toward the formation of allylic radicals. This radical mechanism overcomes issues seen in traditional conjugate allylation processes and selectively installs prenyl fragments at the beta-carbon of enals.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Vasilis Tseliou, Adriana Faraone, Laura Kqiku, Jan Vilim, Gianluca Simionato, Paolo Melchiorre
Summary: This study introduces a novel strategy for biocascades using a single multifunctional enzyme to promote multiple stereoselective steps in a domino process by mastering distinct catalytic mechanisms, simplifying the synthesis of chiral molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Da Xu, Yu Chang, Yidong Liu, Wenling Qin, Hailong Yan
Summary: This study achieved the enantioselective construction of stable VQM intermediates through organocatalyzed bromination, and revealed the mechanistic details of the two sequential events in VQM-involved reactions. The high potential of VQM as axially chiral synthetic reagents in organic chemistry was demonstrated.
Review
Pharmacology & Pharmacy
Yazan Haddad, Marek Remes, Vojtech Adam, Zbynek Heger
Summary: The study utilized variations in 110 crystal structures to assemble eight distinct families highlighting the C-helix orientation in the N-lobe of the EGFR kinase domain. These families shared similar mutational profiles, ligand R-groups facing the C-helix, mutation sites, and DFG domain.
DRUG DISCOVERY TODAY
(2021)
Article
Chemistry, Organic
Martina Sotolova, Martin Kamlar, Marek Remes, Pierre-Yves Geant, Ivana Cisarova, Martin Sticha, Jan Vesely
Summary: An organocatalytic asymmetric domino Michael/alpha-alkylation reaction has been developed for the synthesis of 1,2,3-trisubstituted cyclopentane carbaldehydes. The reaction, catalyzed by chiral secondary amines, exhibits high diastereo- and enantioselectivities.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Applied
Vojtech Docekal, Tereza Koberova, Jan Hrabovsky, Andrea Vopalenska, Robert Gyepes, Ivana Cisarova, Ramon Rios, Jan Vesely
Summary: A new asymmetric organocatalytic cascade reaction was reported for the synthesis of enantiopure chiral boron dipyrromethenes (BODIPYs), with high isolated yields and enantiomeric excesses. The method showed synthetic versatility and was successfully applied to a series of additional transformations of the corresponding optically pure compounds.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Viraj A. Bhosale, Martin Nigrini, Martin Dracinsky, Ivana Cisarova, Jan Vesely
Summary: The study presents a versatile method for the synthesis of chiral 2H-1,4-benzoxazines using chiral phosphoric acid catalysis, achieving high yields and enantioselectivity under mild conditions. This strategy expands on traditional methods and provides access to key intermediates for therapeutic candidates, such as prostaglandin D2 receptor antagonists and MI positive allosteric modulator (PAM) compound VU0486846.
Article
Chemistry, Multidisciplinary
Ivana Miletto, Marta Meazza, Geo Paul, Maurizio Cossi, Enrica Gianotti, Leonardo Marchese, Ramon Rios, Marc Pera-Titus, Robert Raja
Summary: In this study, a designed N-heterocyclic carbene (NHC) catalyst was anchored on mesoporous and hierarchical supports of varying pore sizes to investigate the influence on the benzoin condensation of furfural. The characteristics of the anchored catalysts were examined to rationalize their stability and recyclability using molecular dynamics simulations. The results showed that the catalysts maintained quantitative yields (99%) and complete recyclability after multiple cycles, validating the design rationale.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Multidisciplinary
Klara Kohoutova, Vojtech Docekal, Michael J. Ausserlechner, Nora Kaiser, Andrej Tekel, Raju Mandal, Matej Horvath, Veronika Obsilova, Jan Vesely, Judith Hagenbuchner, Tomas Obsil
Summary: Increased FOXO3 nuclear localization is involved in neuroblastoma chemoresistance and tumor angiogenesis. Inhibition of FOXO3 is a promising strategy for enhancing antitumor immune responses and suppressing therapy resistance in cancer cells. (4-propoxy)phenylpyrimidinylguanidine has been identified as a FOXO3 inhibitor in cancer cells. The synthesis and structure-activity relationship study of its derivatives showed that some compounds are more potent than the parent compound in inhibiting FOXO3-induced gene transcription. These findings may contribute to the development of therapeutics for inhibiting FOX transcription factors.
Article
Chemistry, Multidisciplinary
Martin Kamlar, Michal Urban, Jan Vesely
Summary: Over the past decade, the combination of organocatalysis and transition metal catalysis has become an important tool for synthesizing optically pure compounds with chiral quaternary centers, including spiro heterocyclic molecules. The dominant methods in enantioselective synthesis of spiro heterocyclic compounds involve chiral aminocatalysis, NHC catalysis, as well as non-covalent catalysis using chiral phosphoric acids, thiourea, and squaramide derivatives. This review article provides a summary of enantioselective methods for constructing spirocyclic heterocycles using a combination of organocatalysis and transition metal catalysis.
Article
Chemistry, Organic
Andrea Vopalenska, Vojtech Docekal, Simona Petrzelova, Ivana Cisarova, Jan Vesely
Summary: The present study reports an asymmetric organocascade reaction that efficiently catalyzes the reaction between oxindole-derived alkenes and 3-bromo-1-nitropropane using a bifunctional catalyst. The reaction produces spirooxindole-fused cyclopentanes in moderate-to-good isolated yields (15-69%) with excellent stereochemical outcomes. The synthetic utility of the protocol is demonstrated through additional transformations of the resulting spirooxindole compounds.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Applied
Anastasia Kurbanova, Martin Nigrini, Kinga Golabek, Ondrej Vesely, Jan Vesely
Summary: Synthetic organic chemistry often requires multiple steps and expensive catalysts for the synthesis of functionalised tetrahydropyrans. In this study, we tested zeolites as eco-friendly and industrially relevant catalysts for the synthesis of 2-phenyltetrahydropyran. The results showed that zeolites favor the formation of the desired product, and the reaction kinetics depend on the number of acid sites, rather than the textural properties.
MICROPOROUS AND MESOPOROUS MATERIALS
(2023)
Article
Chemistry, Organic
Ladislav Loska, Vojtech Docekal, Ivana Cisarova, Jan Vesely
Summary: The study presents an asymmetric NHC-catalyzed formal [4 + 2] cycloaddition of heterocyclic alkenes with an azolium-dienolate intermediate. The reaction is achieved without external oxidation of the Breslow intermediate. Good yields (typically about 90%) and stereochemical outcomes (in most cases, dr > 20/1, and ee = 70-99%) were obtained for heterocyclic cyclohexenones. The synthetic utility of the protocol was demonstrated by the scope of heterocyclic alkenes.
Article
Chemistry, Organic
Martin Kamlar, Ivana Cisarova, Jan Vesely
Summary: A Bronsted acid-catalyzed synthesis of tetrasubstituted allenyl compounds decorated with heterocyclic sulfenyl group is reported in this study. The reaction can readily proceed from available propargylic alcohols in the presence of pentacarboxycyclopenatadienes (PCCPs) as organocatalysts. This developed strategy provides tetrasubstituted allene derivatives in high yields and under mild reaction conditions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Martin Nigrini, Viraj A. Bhosale, Ivana Cisarova, Jan Vesely
Summary: In this study, a highly enantioselective desymmetrization of 3-substituted oxetanes was achieved using a confined chiral phosphoric acid as the catalyst. This metal-free process allows for the efficient synthesis of chiral seven-membered 1,4-benzoxazepines with a high degree of enantiocontrol under mild reaction conditions. The developed synthetic strategy demonstrates its synthetic utility in various enantioselective product transformations, proving its effectiveness in diverse scenarios.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Applied
Michael Franc, Ivana Cisarova, Jan Vesely
Summary: The present study investigates an enantioselective cyclization of enals with imidazolone derivatives catalyzed by a combination of achiral Pd(0) complex and chiral secondary amine. Corresponding spirocyclic imidazolones were produced in high yields with moderate diastereoselectivity and excellent enantioselectivity. The developed co-operative catalytic methodology provides a highly substituted spirocyclic scaffold with four stereogenic centers under mild conditions.
Article
Chemistry, Multidisciplinary
Viraj A. Bhosale, Ivana Cisarova, Martin Kamlar, Jan Vesely
Summary: This study presents a novel chiral phosphoric acid (CPA)-catalyzed reaction, allowing for the asymmetric addition of alpha-fluoro(phenylsulfonyl)methane (FSM) derivatives to in situ generated cyclic N-acyliminium. The process demonstrates high stereoselectivity, leading to the formation of biorelevant isoindolinones containing sulfone and fluorine substituents with excellent stereoselectivities.
CHEMICAL COMMUNICATIONS
(2022)