Review
Chemistry, Applied
Sebastian Stiniya, Padinjare Veetil Saranya, Gopinathan Anilkumar
Summary: N-containing compounds are crucial in nature and synthetic organic chemistry, with N-alkylation reactions playing a significant role in pharmaceuticals and industrial chemical syntheses. Iron-catalyzed N-alkylation reactions have gained acceptance for being environmentally friendly, abundant, non-toxic, biocompatible, reusable, and inexpensive. Green protocols, mild reaction conditions, wide substrate scope, and eco-friendly features make iron-catalyzed N-alkylation reactions prominent in various research fields.
APPLIED ORGANOMETALLIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Damiano Tanini, Camilla Dalia, Antonella Capperucci
Summary: The study reports on the on water selenium mediated oxidation of anilines, which leads to nitroarenes or azoxyarenes depending on the selenium reagents used. The mechanistic analysis revealed that Se(iv) species are the active oxidants in the catalytic cycle operating in water, in contrast to previous demonstrations using Se(vi) intermediates in organic solvents.
Article
Chemistry, Organic
Xiaodong Xiong, Jonathan Wong, Ying-Yeung Yeung
Summary: A facile, efficient, and chemoselective synthesis of allylic amides has been developed using allyl bromides activated by silver triflate. The Ritter-type reaction readily proceeds under mild conditions to give various allyl amides. This protocol is also applicable to different nucleophilic partners to yield a wide range of allyl-substituted products in the absence of a base.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Gaurav Badhani, Abhisek Joshi, Subbarayappa Adimurthy
Summary: The study introduces a metal-free method for the synthesis of imines using oxygen as the terminal oxidant, achieving oxidative coupling of amines and alcohols to form C-N, C-S, and C-C bonds. This method features mild reaction conditions and broad applicability.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Luciana Cicco, Marianna Roggio, Marcos Lopez-Aguilar, Marina Ramos-Martin, Filippo Maria Perna, Joaquin Garcia-Alvarez, Paola Vitale, Vito Capriati
Summary: An efficient, selective, and sustainable catalytic method has been developed for the oxidation of activated alcohols to the corresponding carbonyl compounds. The reaction proceeds under mild conditions and yields high product yields.
Review
Chemistry, Applied
Jaume Rostoll-Berenguer, Gonzalo Blay, Jose R. Pedro, Carlos Vila
Summary: This review summarizes recent publications on asymmetric oxidative Mannich reactions using amines as electrophiles, including the different oxidants used and the scope and limitations of the different catalytic systems.
ADVANCED SYNTHESIS & CATALYSIS
(2021)
Article
Chemistry, Multidisciplinary
Sayan Kar, Quan-Quan Zhou, Yehoshoa Ben-David, David Milstein
Summary: Furfural and 5-hydroxymethyl furfural (HMF) can be oxidized to furoic acid and furan-2,5-dicarboxylic acid (FDCA) in water, generating H2 as a byproduct. However, current methods for this process are difficult to control and scale up. A new ruthenium pincer catalyst has been developed for direct oxidation of furfural/HMF to furoic acid/FDCA, with pure H2 produced as a byproduct.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Organic
Madhukar S. Said, Nilesh S. Khonde, Pradeep Kumar, Jayant M. Gajbhiye
Summary: This study reveals a method for the synthesis of trifluoromethyl ketones via the fluoroarene-mediated trifluoromethylation of carboxylic acids. The fluoroarene activates the acid group and generates the fluoride source in situ for the trifluoromethylation reaction. The protocol is safe, metal-free, operates under mild conditions, and does not require external additives to generate trifluoromethyl anion. The transformation shows good functional group tolerance and delivers high yields of trifluoromethyl ketones in both batch and continuous flow processes.
Article
Chemistry, Multidisciplinary
Ramin Ghiai, Sedigheh Alavinia, Ramin Ghorbani-Vaghei, Alireza Gharakhani
Summary: This study presents a novel method for synthesizing a porous polymer stabilizer using Fe3O4 magnetic nanoparticles as templates. The synthesized polymer showed a multi-layered structure and was used as a support for a nickel organometallic complex. The resulting nanocomposite exhibited high selectivity and activity as a heterogeneous catalyst in imine synthesis. The synthesized catalyst could be used for eight cycles without significant loss of catalytic efficiency.
Article
Biochemistry & Molecular Biology
Joel K. Annor-Gyamfi, Ebenezer Ametsetor, Kevin Meraz, Richard A. Bunce
Summary: An efficient synthetic route has been developed for the preparation of highly substituted dihydroquinolines and dihydronaphthyridines through a domino reaction of Morita-Baylis-Hillman acetates with primary aliphatic and aromatic amines. The reaction proceeds at 50-90 degrees C in DMF. The products were isolated in good to excellent yields, with dual reactivity observed in the annulations of MBH acetates incorporating a 2,5-difluorophenyl moiety.
Article
Multidisciplinary Sciences
Robin Fertig, Felix Leowsky-Kuenstler, Torsten Irrgang, Rhett Kempe
Summary: Introducing unknown compound classes is crucial for expanding the chemical space. The authors propose a rational design concept and synthesis of unknown classes of N-heterocyclic compounds. The discovery of reactions is a central topic in chemistry, and the ability to synthesize unexplored compound classes is particularly fascinating. N-Heterocyclic compounds are highly important due to their wide applications in life and material sciences. The authors introduce a sequential three-component reaction, classes of N-heterocyclic compounds, and the regenerative cyclisation synthesis concept.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Inorganic & Nuclear
Diptangshu Datta Mal, Debabrata Pradhan
Summary: The facile synthesis of an imine compound through a greener route remains a challenging task. This study demonstrates the successful synthesis of cobalt-doped manganese tungstate as a recyclable catalyst for imine synthesis in a nonaqueous and nonacidic environment. The catalyst exhibits high activity, stability, and recyclability, making it suitable for industrial applications.
INORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Yanling Zheng, Yang Long, Huihua Gong, Jiaqi Xu, Chunchun Zhang, Haiyan Fu, Xueli Zheng, Hua Chen, Ruixiang Li
Summary: In this study, the divergent transformations of 1,3-diols with arylhydrazines were reported, which selectively synthesized pyrazoles and 2-pyrazolines via acceptorless dehydrogenative coupling reactions using Ru3(CO)12/NHC-phosphinephosphine catalytic systems. The reactions showed low catalyst loading, high selectivity, wide substrate scope, and good yields, with only water and hydrogen gas (H2) as the byproducts.
Article
Chemistry, Organic
Hiroyuki Mutoh, Shu Nakamura, Koichi Hagiwara, Masayuki Inoue
Summary: Limonoids 1 and 2 share a 6/6/6/5-membered ABCD ring system and a six-membered oxacycle, but differ in their C9-stereochemistries. A novel radical-based strategy was developed to construct the pentacyclic skeletons of 1 and 2, by coupling oxacycle-fused A-ring and enyne fragments to produce radical precursors 4a-4c with different C7-oxygen functionalities, which then participated in a radical cascade reaction to cyclize the C9-diastereomeric BCD rings.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Xiaofan Wang, Bingyue Zhao, Lingzhi Xu, Xuemin Li, Haofeng Shi, Yunfei Du
Summary: In the presence of TBHP, the reaction of arylaldehydes and arylamines with NH4SCN results in a divergent Strecker synthesis, yielding aminonitriles and iminonitriles. The notable aspect of this modified Strecker reaction is the use of non-toxic NH4SCN as the cyanide source.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Multidisciplinary
Sarah Bierbaumer, Luca Schmermund, Alexander List, Christoph K. Winkler, Silvia M. Glueck, Wolfgang Kroutil
Summary: In this study, a concurrent biocatalytic reduction and photocatalytic oxidation process was demonstrated. By coupling the enantioselective biocatalytic sulfoxide reduction and light-dependent sulfoxidation, a cyclic deracemization process for nonracemic sulfoxides was achieved with excellent conversions and optical purity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Physical
Nico D. Fessner, Christopher Grimm, Matic Srdic, Hansjoerg Weber, Wolfgang Kroutil, Ulrich Schwaneberg, Anton Glieder
Summary: This study explores the synthetic potential of human P450 3A4 in diversifying natural product classes, resulting in the identification of 31 authentic human metabolites. With efficient expression levels in P. pastoris, this biocatalyst shows promising results for modifying natural products in a one-step fashion.
Article
Chemistry, Physical
Willem B. Breukelaar, Nakia Polidori, Amit Singh, Bastian Daniel, Silvia M. Guleck, Karl Gruber, Wolfgang Kroutil
Summary: The biocatalytic reduction of oxime moiety to amine group has recently been discovered, but the reaction pathway remained unclear. Through studying crystal structures, molecular dynamics simulations, and investigating biocatalytic cascades and intermediates, evidence suggests that the reaction proceeds via an imine intermediate rather than a hydroxylamine intermediate. The imine is further reduced by the ene-reductase to produce the amine product. A non-canonical tyrosine residue contributes to the catalytic activity by protonating the hydroxyl group of the oxime in the first reduction step.
Article
Chemistry, Applied
Philipp Petermeier, Christoph Kohlfuerst, Ana Torvisco, Roland C. C. Fischer, Alejandro Mata, Doris Dallinger, C. Oliver Kappe, Joerg H. H. Schrittwieser, Wolfgang Kroutil
Summary: Substituted piperidine rings are efficiently prepared with multiple stereocentres using multi-enzymatic and chemo-enzymatic methods from achiral diketoester precursors. Highly enantioselective transamination and diastereoselective reduction processes enable the synthesis of optically pure piperidines. This approach offers a more streamlined and efficient route for the synthesis of trisubstituted piperidines with potential applications in drug discovery.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Applied
P. Petermeier, C. Kohlfuerst, A. Torvisco, R. C. Fischer, A. Mata, D. Dallinger, C. O. Kappe, J. H. Schrittwieser, W. Kroutil
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Applied
Mathias Pickl, Markus Ebner, Samantha Gittings, Pere Clapes, Wolfgang Kroutil
Summary: Although optical pure amino alcohols are highly demanded, their synthesis remains challenging due to the requirement of elaborate protection strategies. This study presents a multi-enzymatic methodology that allows the synthesis of enantioenriched 1,3-amino alcohols from commodity chemicals. By utilizing a Type I aldolase and enzymatic transamination, both diastereomers of the 1,3-amino alcohol motif were accessible, resulting in the desired amino alcohols with high enantioselectivity.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Biochemistry & Molecular Biology
Sarah A. Berger, Christopher Grimm, Jonathan Nyenhuis, Stefan E. Payer, Isabel Oroz-Guinea, Joerg H. Schrittwieser, Wolfgang Kroutil
Summary: Mass spectrometry-based high-throughput screening methods combine the advantages of photometric or fluorometric assays and analytical chromatography. However, their limited use is due to the requirement of specialised and expensive hardware. We demonstrate that a common platform, single-quadrupole HPLC-MS, can be used for rapid analysis of diverse biotransformations by flow-injection mass spectrometry (FIA-MS), providing validated activity and selectivity information with a one-minute analytical run time per sample. Our results establish FIA-MS as a versatile and reliable alternative to traditional methods for screening enzymatic reactions.
Review
Chemistry, Physical
Veronique Alphand, Willem J. H. van Berkel, Valentina Jurkas, Selin Kara, Robert Kourist, Wolfgang Kroutil, Francesco Mascia, Marc M. Nowaczyk, Caroline E. Paul, Sandy Schmidt, Jelena Spasic, Paula Tamagnini, Christoph K. Winkler
Summary: The recent increase of interest in photocatalysis has expanded to biocatalysis and led to a surge in the development of light-dependent enzyme-mediated or enzyme-coupled processes. Reviewing the progress in photobiocatalysis, we suggest categorizing it into different disciplines and providing guidelines for reporting research results and performing photobiocatalytic reactions. Overall, we believe that this field enhances the diversity of biocatalytic reactions and harnesses the selectivity of enzymes in photocatalysis. We anticipate that the ongoing enthusiasm for light-dependent enzymatic processes will uncover new photobiocatalytic mechanisms, complementing biocatalysis with novel bond-forming reactions and innovative strategies for utilizing light as a sustainable energy source.
Article
Chemistry, Organic
Beata Zdun, Tamara Reiter, Wolfgang Kroutil, Pawel Borowiecki
Summary: We developed chemoenzymatic routes using low-cost starting materials and enzyme preparations to synthesize tenofovir. The key step involved stereoselective reduction or kinetic resolution using alcohol dehydrogenase or lipase as biocatalysts. By employing immobilized lipase in a mixture of vinyl acetate and toluene, the desired (R)-ester was obtained with high yield and optical purity. Alternatively, reduction of a ketone using lyophilized E. coli cells containing recombinant alcohol dehydrogenase resulted in excellent conversion and yield of the corresponding (R)-alcohol. The enzymatic strategy could be applied in the synthesis of tenofovir prodrug derivatives.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Correction
Chemistry, Physical
Stefan Simic, Migle Jakstaite, Wilhelm T. S. Huck, Christoph K. Winkler, Wolfgang Kroutil
Article
Chemistry, Multidisciplinary
Aleksandra Rudzka, Beata Zdun, Natalia Antos, Lia Martinez Montero, Tamara Reiter, Wolfgang Kroutil, Pawel Borowiecki
Summary: There is a need for biocatalysts capable of transferring hydrogen to prepare optically pure alcohols, especially for sterically demanding ketones. This study describes the biocatalytic potential of an anti-Prelog (R)-specific variant of Lactobacillus kefir ADH as a whole-cell biocatalyst for the reduction of prochiral carbonyl substrates. The results show that the biocatalyst exhibits activity towards a variety of ketones, producing optically active alcohol products with high conversion and excellent stereoselectivity.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Christopher Grimm, Simona Pompei, Kristina Egger, Michael Fuchs, Wolfgang Kroutil
Summary: Lignin-derived aryl methyl ethers have potential as carbon sources in chemistry. An alternative method for their demethylation is through cobalamin-dependent enzymes, which require a methyltransferase and a carrier protein. Fusion proteins, connecting the methyltransferase with the corrinoid-binding protein, showed better performance than separate proteins, enabling a simpler protocol for demethylation. The fusion enzyme has promising applications in diversifying natural products and valorizing lignin.
Article
Chemistry, Physical
Willem B. Breukelaar, Nakia Polidori, Amit Singh, Bastian Daniel, Silvia M. Glueck, Karl Gruber, Wolfgang Kroutil
Summary: The biocatalytic reduction of oxime to amine has been observed in ene-reductases transforming alpha-oximo beta-keto esters. Through structural analysis, molecular dynamics simulations, biocatalytic cascades, and investigation of possible intermediates, it has been determined that the reaction proceeds via an imine intermediate and not through a hydroxylamine intermediate. A non-canonical tyrosine residue in ene-reductase OPR3 was found to play a role in protonating the hydroxyl group of the oxime in the first reduction step.
Article
Chemistry, Multidisciplinary
Emmanuel Cigan, Jakob Pletz, Sarah A. Berger, Bettina Hierzberger, Michael Grilec-Zlamal, Alexander Steiner, Isabel Oroz-Guinea, Wolfgang Kroutil
Summary: This study demonstrates an efficient access to the morphinan scaffold using a combination of organic synthesis and enzymatic reactions. The synthesis of a medicinally important compound class, promorphinans, was achieved by minimizing protecting group techniques and utilizing biocatalysis.
Article
Chemistry, Physical
Pawel Borowiecki, Aleksandra Rudzka, Tamara Reiter, Wolfgang Kroutil
Summary: In this study, a sequential chemoenzymatic one-pot two-step deracemization protocol was developed for synthesizing enantiomeric Lisofylline. The protocol involved a tandem bi-enzymatic oxidation-reduction reaction sequence, which catalyzed the oxidation of Lisofylline to pentoxifylline using laccase and a redox mediator, and the subsequent reduction of pentoxifylline to generate enantiomeric Lisofylline using alcohol dehydrogenases. The method showcased high conversion rates and synthesis efficiency, providing both antipodes of Lisofylline in good yields and high enantiomeric excess.
CATALYSIS SCIENCE & TECHNOLOGY
(2022)