Article
Chemistry, Multidisciplinary
Georg Niggemeyer, Anastasia Knyazeva, Raphael Gasper, Dale Corkery, Pia Bodenbinder, Julian J. Holstein, Sonja Sievers, Yao-Wen Wu, Herbert Waldmann
Summary: Design and synthesis of pseudo-natural products through recombination of natural product fragments enables the discovery of novel biologically relevant chemical matter. In this study, the combination of this principle with macrocycle formation was described, leading to the efficient synthesis of 163 macrocyclic pseudo-natural products. Biological investigation revealed their potent inducers of autophagy-related processes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Zahra Zareshahrabadi, Mohammad Khorram, Keyvan Pakshir, Ali-Mohammad Tamaddon, Mahboobeh Jafari, Hasti Nouraei, Niloofar Torabi Ardekani, Neda Amirzadeh, Cambyz Irajie, Alireza Barzegar, Aida Iraji, Kamiar Zomorodian
Summary: This study aimed to develop a novel and cost-effective IONPs@CS-AmB formulation to enhance AmB delivery performance and reduce drug dosage and adverse effects. The results showed that IONPs@CS-AmB exhibited significant antifungal activity and had higher biocompatibility compared to plain AmB and fungizone.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Review
Chemistry, Multidisciplinary
Suman Chakrabarty, Evan O. Romero, Joshua B. Pyser, Jessica A. Yazarians, Alison R. H. Narayan
Summary: The total synthesis of structurally complex natural products remains an exciting area of research, with recent advancements in biocatalysis allowing for the application of enzymes in constructing complex molecules. The utilization of enzymes alongside small molecule-based approaches has enabled concise chemoenzymatic routes to natural products, demonstrating the potential for selective oxidation reactions and late-stage diversification of complex scaffolds.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Acoustics
Sasadhar Majhi
Summary: Total synthesis is a method for preparing complex natural products from simple materials, which plays a crucial role in confirming complex structures and preparing rare bioactive substances. The use of ultrasound as a non-polluting energy source in the synthesis of bioactive natural products highlights its potential in sustainable and pharmaceutical chemistry.
ULTRASONICS SONOCHEMISTRY
(2021)
Review
Biochemistry & Molecular Biology
Thaddeus Q. Paulsel, Gavin J. Williams
Summary: Polyketide natural products have great potential as pharmaceutical targets and molecular tools for human health and disease research. Despite the well-understood biosynthetic logic of polyketide synthases, the synthesis of designer polyketides remains challenging due to various issues. Chemical enzymatic synthesis of PKSs has provided valuable insights into enzymatic promiscuity and mechanistic activity and has successfully yielded natural product derivatives. Combining chemical synthesis and enzymology can further improve polyketide synthetic biology approaches.
Article
Microbiology
Kevin Brunet, Cheikh A. B. Diop, Alexia Chauzy, Noemie Prebonnaud, Sandrine Marchand, Blandine Rammaert, Frederic Tewes
Summary: This study evaluated the effect of the combination of amphotericin B (AmB) and various non-ionic surfactants on the activity of AmB against Mucorales, the toxicity on eukaryotic cells, and the modification of AmB aggregation states. The results showed that PEG15HS increased the efficacy of AmB against Mucorales without increasing its toxicity.
Review
Chemistry, Organic
Sasadhar Majhi
Summary: The development of more effective synthetic technologies and sustainable methodologies is a vital driving force for chemists to discover novel synthetic protocols. Flow chemistry and flow photochemistry have emerged as powerful tools to promote valuable transformations in the total synthesis of natural products.
CURRENT ORGANIC CHEMISTRY
(2023)
Article
Polymer Science
Daniela Ailincai, Irina Rosca
Summary: This study investigates the preparation of hydrogels and formulations for the treatment of Candida infections using piperonyl-imino-chitosan derivatives and Amphotericin B drug. The hydrogels were obtained through a reaction of chitosan with piperonal monoaldehyde, while the formulations were obtained through in situ hydrogelation of chitosan with piperonal in the presence of Amphotericin B. Structural characterization revealed the formation of imine units, and supramolecular characterization showed hydrophilic/hydrophobic segregation. The systems exhibited biodegradability, high swelling ability, sustained release of the drug, and promising antifungal activity against Candida strains.
Review
Medicine, General & Internal
Beata Sienkiewicz-Oleszkiewicz, Malgorzata Salamonowicz-Bodzioch, Justyna Slonka, Krzysztof Kalwak
Summary: The interaction between antifungal drugs and common drugs is an important issue in pediatric hemato-oncology. This review focuses on the interaction between antifungal agents and treatment drugs for acute lymphoblastic leukemia, and found that liposomal amphotericin B has a favorable safety profile.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Chemistry, Multidisciplinary
Debobrata Paul, Ashis Kundu, Sanu Saha, Rajib Kumar Goswami
Summary: This feature article highlights total synthesis as a reliable tool for confirming the structure of natural products. Despite advances in spectroscopic techniques, structural misassignments of natural products remain common. Recent case studies have shown that chemical synthesis can be used to revise the structures of natural products.
CHEMICAL COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Unai Caballero, Elena Eraso, Guillermo Quindos, Nerea Jauregizar
Summary: The study found that combinations of amphotericin B with anidulafungin or caspofungin provide better killing of Candida auris infections compared to monotherapy, with a lower dose requirement for amphotericin B.
Article
Chemistry, Multidisciplinary
Li Gao, Joyce C. M. Meiring, Constanze Heise, Ankit Rai, Adrian Mueller-Deku, Anna Akhmanova, Julia Thorn-Seshold, Oliver Thorn-Seshold
Summary: Optical methods to modulate microtubule dynamics have the potential to decrypt the roles of the cytoskeleton in biology with high resolution. However, the development of optical microtubule stabilisers is still limited. In this study, we introduce STEpos as GFP-orthogonal, light-responsive microtubule stabilisers, which significantly improve potency, solubility, and ease-of-use compared to previous stabilisers. These reagents can greatly contribute to high-precision research in cytoskeleton biophysics, cargo transport, cell motility, cell division, development, and neuroscience.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Organic
Sasadhar Majhi
Summary: Natural products are important sources of potential drug leads, and total synthesis in the laboratory confirms complex structures but poses challenges due to complexity and stereochemistry. Microwave irradiation, a greener tool, reduces reaction time, increases product purities, improves reproducibility, simplifies work-up methods, and minimizes unwanted side reactions, sparking its application in the total synthesis of bioactive natural products.
CURRENT ORGANIC CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Yanan Du, Anyarat Thanapipatsiri, Kenichi Yokoyama
Summary: Nucleoside natural products have diverse biological activities and can be used for various applications, including medicine and agriculture. Previous studies have revealed the biosynthetic mechanisms of these nucleosides, involving early steps classified into two types and downstream tailoring enzymes for structural diversity. By investigating two enzymes representing these types of modifications, it is possible to discover putative nucleoside biosynthetic gene clusters and predict core nucleoside structures, suggesting the potential for future discovery of novel nucleoside natural products.
Article
Microbiology
Roya Vahedi-Shahandashti, Anna-Maria Dietl, Ulrike Binder, Markus Nagl, Reinhard Wuerzner, Cornelia Lass-Floerl
Summary: This study found that Aspergillus terreus isolates defined as susceptible to amphotericin B (AMB) therapy based on minimum inhibitory concentration (MIC) may comprise tolerant phenotypes, explaining the poor outcomes of AMB treatment.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Article
Chemistry, Multidisciplinary
Nicole Hauser, Michael A. Imhof, Sarah S. Eichenberger, Tomas Kundig, Erick M. Carreira
Summary: The first total syntheses of the indole diterpenoids (+)-shearinine G and D were achieved through late-stage coupling, diastereoselective intramolecular cyclopropanation, Sharpless dihydroxylation/Achmatowicz reaction, and Prins cyclization. Tuning of the substituents on the parent arylcarboxaldehyde led to divergent products, further transformed into shearinines G and D, with unexpected stereochemical outcomes in the Riley-type oxidation of a bicyclic enone.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Editorial Material
Chemistry, Multidisciplinary
Erick M. Carreira
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Nicolas Muller, Benedikt S. Schreib, Sebastian U. Leutenegger, Erick M. Carreira
Summary: In this study, the palladium-catalyzed aminoalkynylation of electronically unbiased olefins with iodoalkynes was reported. Using the picolinamide auxiliary, the syn-selective aminoalkynylation of mono-, di-, and trisubstituted alkenes was achieved, leading to the formation of corresponding pyrrolidines in high yield and single diastereomers. The picolinamide also allowed for the rapid synthesis of functionalized olefins and subsequent Pictet-Spengler reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Moritz E. Hansen, Samuel O. Yasmin, Susanne Wolfrum, Erick M. Carreira
Summary: The first total syntheses of tricyclic mutanobactins A and B, lipopeptides incorporating a thiazepanone, isolated from Streptococcus mutans, a member of the human oral microbiome, were reported. These natural products were rapidly delivered through a cascade of cyclization reactions using a solid-phase peptide synthesis (SPPS) based route. This versatile process was also used for a streamlined synthesis of mutanobactin D. Additionally, an independent synthesis of a truncated mutanobactin A analog, utilizing a novel thiazepanone amino acid building block, was provided.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Nils Trapp, Michael Worle, Bernd Kuhn, Paul Gerber, Raffael Vorberg, Erick M. M. Carreira, Klaus Mueller
Summary: The molecular and crystal structures of 19 N-alkyl-substituted pipecolamide derivatives, including partial fluorination patterns, were presented. The different fluorination patterns in the N-alkyl group resulted in diastereomeric compounds with distinct crystal and molecular structures. The study also revealed an extraordinary conformational diversity in the various N-alkylpiperidine units, and provided insight into consistent conformational patterns and their modulation factors.
HELVETICA CHIMICA ACTA
(2023)
Article
Chemistry, Multidisciplinary
Supratim Ghosh, Avtar Changotra, David A. Petrone, Mayuko Isomura, Erick M. Carreira, Raghavan B. Sunoj
Summary: In this study, the mechanism of a chiral Ir-phosphoramidite-catalyzed asymmetric reductive deoxygenation reaction was investigated using density functional theory. It was found that Bi(OTf)3 promotes ionic and noncovalent interactions, which play a crucial role in nucleophile selectivity.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
David M. Fischer, Henry Lindner, Willi M. Amberg, Erick M. Carreira
Summary: Intermolecular cyclopropanation of mono-, di-, and trisubstituted olefins with alpha-bromo-beta-ketoesters and alpha-bromomalonates under organophotocatalysis is reported. The transformation exhibits broad functional group tolerance, producing highly substituted cyclopropanes. Mechanistic investigations, including Stern-Volmer quenching, quantum yield determination, and deuteration experiments, provide insights into the catalytic cycle.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Marlene Fadel, Erick M. Carreira
Summary: The first total synthesis of (+)-pedrolide, a tigliane-derived diterpenoid featuring an unprecedented 5-5-6-6-3 carbon skeleton, was achieved. A key step in the synthesis involved the construction of the bicyclo[2.2.1]heptane core via an intramolecular cyclopentadiene-Diels-Alder cycloaddition. A norbornadiene was used as a surrogate for cyclopentadiene, and the unmasking of the cyclopentadiene was achieved through a complex Diels-Alder reaction cascade. This synthesis also provided a novel approach to a densely functionalized carane in an efficient and enantioselective manner.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Editorial Material
Chemistry, Multidisciplinary
Erick M. Carreira
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Sven M. Papidocha, Hendrik H. Bulthaupt, Erick M. Carreira
Summary: The first total synthesis of heavily oxidized cassane-type diterpenoids, neocaesalpin A, AA, and nominal neocaesalpin K, was achieved using a redox-flexible platform as a key intermediate. The synthesis involved an intermolecular Diels-Alder reaction and a novel late-stage oxidation method for furfuryl acetate.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Henry Lindner, Willi M. Amberg, Erick M. Carreira
Summary: In this study, unactivated olefins are converted into alkyl azides using bench-stable NaN3 in the presence of FeCl3·6H2O under blue-light irradiation. The reaction exhibits anti-Markovnikov selectivity and can be conducted under mild ambient conditions in the presence of air and moisture.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Hendrik H. Bulthaupt, Fabian Glatz, Sven M. Papidocha, Chunyan Wu, Shawn Teh, Susanne Wolfrum, Lucia Balazova, Christian Wolfrum, Erick M. Carreira
Summary: This study reports the synthesis and enantioselectivity of a series of compounds, and reveals the stimulating effect of one of the compounds on the respiration of brown adipocytes, which has potential applications in obesity treatment.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
David M. Fischer, Manuel Freis, Willi M. Amberg, Henry Lindner, Erick M. Carreira
Summary: We have developed a method for difunctionalization of unactivated, terminal olefins using intermolecular addition of alpha-bromoketones, -esters, and -nitriles followed by formation of 4- to 6-membered heterocycles with pendant nucleophiles. The reaction can be conducted with alcohols, acids, and sulfonamides as nucleophiles, yielding products with 1,4 functional group relationships that can be further manipulated. The reaction employs a benzothiazinoquinoxaline organophotoredox catalyst at a low catalyst loading and is tolerant to air and moisture.
Article
Chemistry, Multidisciplinary
Monica Guberman, Miroslav Kosar, Anahid Omran, Erick M. Carreira, Marc Nazare, Uwe Grether
Summary: Labeled chemical probes are crucial for the development and commercialization of drugs. They play a significant role in various research phases and provide valuable tools for specific application needs. The reverse-design approach enables the generation of high-quality probes based on previously optimized small molecules, fostering collaborations between academia and industry.
Article
Chemistry, Multidisciplinary
David M. Fischer, Moritz Balkenhohl, Erick M. Carreira
Summary: The cycloisomerization of beta-, gamma-, and delta-unsaturated N-acyl sulfonamides to N-sulfonyl lactams and imidates using a CoIII(salen) catalyst with t-BuOOH or air as the oxidant is reported in this study. The method exhibits good functional group tolerance and provides a new class of cyclic building blocks. The strong solvent dependence of the transformation and the synthetic versatility of the N-sulfonyl imidate product class are highlighted.