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
Biology
Ibrahim Shalayel, Naoual Leqraa, Veronique Blandin, Yannick Vallee
Summary: Complex mixtures of oligomers and polymers can be obtained from simple molecular bricks at the origin of life. This study presents an example of polymerization reactions using two amidonitriles derived from cysteine, Cys-Ala-CN and Cys-Met-CN. The condensation reactions between thiol and nitrile groups result in polymers containing amide bonds and/or thiazolines. The identification of macrocycles, including the largest one with sixteen residues, was achieved using MALDI-TOF mass spectrometry. These findings suggest that complex mixtures formed on the primitive Earth and the subsequent selection process may have been more crucial for the origin of life than the synthesis of pre-biological species themselves.
Article
Plant Sciences
Ozlem Demirkiran, Jehad Almaliti, Tiago Leao, Gabriel Navarro, Tara Byrum, Frederick A. Valeriote, Lena Gerwick, William H. Gerwick
Summary: Three new compounds were isolated from a marine cyanobacterium collected in Panama, including portobelamides A and B, AMOYA, Hiva, and caciqueamide. Portobelamide A exhibited good cytotoxicity against H-460 human lung cancer cells in experiments.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Chemistry, Multidisciplinary
Otoka Shamoto, Keiji Komuro, Naoto Sugisawa, Ting-Ho Chen, Hiroyuki Nakamura, Shinichiro Fuse
Summary: In this study, we propose a unconventional approach to peptide cyclization using acylammonium species generated from inexpensive and less wasteful Me2NBn and ClCO(2)i-Pr. Our method shows rapid activation of the C-terminus of cyclization precursors by an acylammonium ion, enabling rapid cyclization of difficult peptides without degradation or dimerization. Compared to previous reports, our approach demonstrates superior ease of purification, productivity, and reaction mass efficiency. Furthermore, we successfully synthesized a previously reported versicotide D analogue and propose the revision of its assigned stereostructure based on our data.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Bi Bali Judicael Tra, Abolle Abolle, Vincent Coeffard, Francois-Xavier Felpin
Summary: This paper presents a divergent continuous-flow approach for the biomimetic oxidative cyclization of reticuline-type alkaloids to aporphine and morphinandienone natural products using hypervalent iodine(III) reagents. The method allows for the selective synthesis of target products based on detailed knowledge of the reaction mechanisms, providing robust conditions for the preparation of natural products.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Medicinal
Ricardo Ribeiro, Eugenia Pinto, Carla Fernandes, Emilia Sousa
Summary: Marine cyclic peptides are a diverse group of compounds with broad antimicrobial activities, showing promising potential as novel therapeutic agents. These compounds have unique structural characteristics and have demonstrated interesting antimicrobial activities against drug-resistant microorganisms. Marine cyclic peptides are not only potent in vitro, but also show promising results in vivo, making them an important resource for the development of new antimicrobial agents.
Review
Chemistry, Multidisciplinary
Antonella lenia Alfano, Heiko Lange, Margherita Brindisi
Summary: The formation of amide bonds is essential in organic and synthetic medicinal chemistry. In recent years, the application of flow chemistry in amide bond formation has shown significant advantages and potential for development. This review summarizes and compares various methods and discusses future needs and prospects for sustainable synthesis.
Article
Chemistry, Multidisciplinary
Patrick A. Haack, Kirsten Harmrolfs, Chantal D. Bader, Ronald Garcia, Antonia P. Gunesch, Sibylle Haid, Alexander Popoff, Alexander Voltz, Heeyoung Kim, Ralf Bartenschlager, Thomas Pietschmann, Rolf Mueller
Summary: In this study, we discovered a novel myxobacterial natural product called thiamyxins, which possess potent antiviral activity. We elucidated the structure of thiamyxins and proposed a concise biosynthesis model. Thiamyxins demonstrated effective inhibition against RNA viruses such as corona, zika, and dengue virus, while exhibiting low cytotoxicity on human cell lines, indicating their potential for further development.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Nutrition & Dietetics
Maria Sorokina, Kira S. McCaffrey, Erin E. Deaton, Guoying Ma, Jose M. Ordovas, Penelope M. Perkins-Veazie, Christoph Steinbeck, Amnon Levi, Laurence D. Parnell
Summary: This manuscript introduces a catalog of 1,679 small molecules occurring in watermelon and their cheminformatics analysis for diverse features, highlighting the importance of this catalog for precision nutrition and plant breeding efforts. Improved and comprehensive collections of natural products accessible to the public will be especially useful for researchers in nutrition, cheminformatics, bioinformatics, and drug development.
FRONTIERS IN NUTRITION
(2021)
Review
Chemistry, Medicinal
Salar Hafez Ghoran, Fatemeh Taktaz, Emilia Sousa, Carla Fernandes, Anake Kijjoa
Summary: Marine-derived fungi are unique sources of bioactive secondary metabolites, particularly peptides, with diverse structures and biological activities. This review summarizes the literature on marine fungal peptides from January 1991 to June 2023, covering their chemical characteristics, sources, and biological and pharmacological activities. Among 30 genera, Aspergillus was found to produce the highest number of peptides, followed by Penicillium, Acremonium, Eurotium, Trichoderma, Simplicillium, and Beauveria. The predominant activity of the reported marine peptides was cytotoxicity against human cancer cell lines, followed by antibacterial, antifungal, antiviral, anti-inflammatory, and enzyme inhibition activities.
Article
Agricultural Engineering
Hao Zhou, Qin Liu, Xiuhong Zhong, Yaqi Chu, Zhaojiang Wang, Yanqin Wang
Summary: Flow fractionation (FF) technology can be used to process the main components of lignocellulosic biomass for efficient utilization. Treatment of poplar wood with FF results in high purity products and greatly improved enzymatic digestibility, while preserving the structure of lignin and successfully transforming it into hydrocarbons.
INDUSTRIAL CROPS AND PRODUCTS
(2021)
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
Engineering, Chemical
Masashi Tanaka, Masahiro Hosoya, Atsushi Manaka, Naoki Tsuno
Summary: This paper presents a case study on integrating a continuous flow reaction with continuous crystallization, demonstrating the successful synthesis and crystallization of Fmoc-L-Phe-L-Phe-OMe under continuous conditions using an MSMPR crystallizer. The integration system showed feasibility for manufacturing.
CHEMICAL ENGINEERING RESEARCH & DESIGN
(2021)
Article
Chemistry, Multidisciplinary
Sebastian Dengler, Ryan T. Howard, Vasily Morozov, Christos Tsiamantas, Wei-En Huang, Zhiwei Liu, Christopher Dobrzanski, Vojislava Pophristic, Sophie Brameyer, Celine Douat, Hiroaki Suga, Ivan Huc
Summary: Expanding the chemical diversity of peptide macrocycle libraries through the inclusion of a large aromatic helical foldamer has been implemented. A hybrid macrocyclic nanomolar binder to the C-lobe of the E6AP HECT domain was selected, and its crystal structure and molecular dynamics simulations revealed an intriguing reciprocal helical folding of the peptide and foldamer. The results represent a significant extension in the chemical space amenable to display selection and highlight the potential benefits of incorporating an aromatic foldamer into a peptide macrocycle for protein recognition.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
George J. Saunders, Andrei K. Yudin
Summary: The passive membrane permeability of macrocycles can be greatly improved by incorporating heterocyclic grafts. However, the permeability does not scale linearly with the number of heterocycles, highlighting the subtleties of the conformation-property relationship in this class of molecules.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Organic
Liwei Cao, Mikhail Kabeshov, Steven Ley, Alexei A. Lapkin
BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
(2020)
Review
Chemistry, Multidisciplinary
Kwang-Yoon Ko, Zoe E. Wilson, Margaret A. Brimble
Summary: Researchers have synthesized and established the absolute stereochemistry of Callyspongiolide, a macrolide natural product with promising caspase-independent bioactivity, contributing to the wider field of macrolide synthesis.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Applied
Steven Ley, Yiding Chen, Alan Robinson, Benjamin Otter, Edouard Godineau, Claudio Battilocchio
Summary: The agrochemical sector faces massive constraints in cost-effective and sustainable production at an increasing scale within a highly complex environment. The application of flow chemistry technology can offer clear advantages in chemical processes, especially in the early stages of R&D for agrochemicals. The value of flow chemistry for businesses is evident, and the number of reported examples in the literature is expected to continue increasing in the agrochemical industry.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Sougata Roy, James Sipthorp, Bidesh Mahata, Jhuma Pramanik, Marco L. Hennrich, Anne-Claude Gavin, Steven Ley, Sarah A. Teichmann
Summary: This study investigates the role of pregnenolone in prostate cancer and immune cells, suggesting that pregnenolone may promote the development of castration-resistant prostate cancer while also regulating CD8(+) T cell function.
Article
Plant Sciences
Emma K. Davison, Caitlin E. Shepperson, Zoe E. Wilson, Margaret A. Brimble
Summary: The researchers successfully synthesized multiple natural products using a biomimetic spiroketalization approach, revealing their biosynthetic pathways and proposing a scalable and efficient synthesis method.
JOURNAL OF NATURAL PRODUCTS
(2021)
Article
Chemistry, Organic
Oliver M. Griffiths, Henrique A. Esteves, Yiding Chen, Karin Sowa, Oliver S. May, Peter Morse, David C. Blakemore, Steven Ley
Summary: Executing photoredox reactions in flow can improve reaction concentration, reduce reaction time, achieve better yields, facilitate catalyst preparation, and expand substrate scope, demonstrating broad applicability.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Harry R. Smallman, Jamie A. Leitch, Tom McBride, Steven Ley, Duncan L. Browne
Summary: Continuous flow systems have unique advantages in the generation and manipulation of sensitive reactive intermediates like ketenes, and various methods have been developed in the past decade for generating ketenes in continuous flow using chemical, thermal, and photochemical activation modes. This article discusses these advancements and the downstream reactivity of ketenes in continuous flow technology.
Article
Engineering, Environmental
Nam Nghiep Tran, Marc Escriba Gelonch, Shu Liang, Zihao Xiao, Mohammad Mohsen Sarafraz, Marina Tisma, Hans-Jurgen Federsel, Steven V. Ley, Volker Hessel
Summary: This study investigated enzymatic pre-treatment of grease trap waste for biodiesel production, reducing FFA levels through an esterification reaction. Results showed that using commercial enzymes in continuous-flow experiments achieved better FFA reduction than batch processes. The continuous-flow reactors were also more time-efficient, completing experiments in less than 1.5 days compared to 6 days for batch processes.
CHEMICAL ENGINEERING JOURNAL
(2021)
Article
Chemistry, Multidisciplinary
Pia Mueller, Adam D. Clayton, Jamie Manson, Samuel Riley, Oliver S. May, Norman Govan, Stuart Notman, Steven Ley, Thomas W. Chamberlain, Richard A. Bourne
Summary: The study compared the performance of four different multi-objective optimisation algorithms in chemical reaction optimisation, finding that EIMEGO achieved the highest hypervolume with the lowest number of experiments, while TSEMO performed better in cases with three objectives.
REACTION CHEMISTRY & ENGINEERING
(2022)
Article
Chemistry, Organic
Oliver M. Griffiths, Steven V. Ley
Summary: The photocatalytic generation of N-centered radicals has been employed for the synthesis of N-heterospirocycles, offering a reliable method for the construction of beta-spirocydic pyrrolidines from N-allylsulfonamides and alkenes. This study demonstrates the successful construction of various beta-spirocyclic pyrrolidines, including drug derivatives, with moderate to very good yields. Derivatization of the products and a viable scale-up procedure using flow chemistry techniques have also been achieved.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Pia Mueller, Aikaterini Vriza, Adam D. Clayton, Oliver S. May, Norman Govan, Stuart Notman, Steven V. Ley, Thomas W. Chamberlain, Richard A. Bourne
Summary: Automated platforms enable fast and efficient optimization of chemical systems with single and multiple objectives. In this study, we demonstrate the application of automated optimization platforms for chemical screening of sulfide oxidations in flow. The identification of unique optima for each substrate emphasizes the importance of rapid and individual experimental optimization for successful compound screening.
REACTION CHEMISTRY & ENGINEERING
(2023)
Article
Chemistry, Multidisciplinary
Samuel L. Bourne, Franz Amann, Steven V. Ley
Summary: This article provides an overview of the factors contributing to the rise of flow chemistry in the pharmaceutical industry over the past two decades. It highlights the challenges faced by the industry and how scientific progress has helped to overcome them. Current trends and examples of progress at CARBOGEN AMCIS are discussed, giving a speculative glimpse into the future of drug development and manufacturing.
Article
Chemistry, Multidisciplinary
Ricardo Labes, Julio C. Pastre, Richard J. Ingham, Claudio Battilocchio, Henrique M. Marcon, Mariana C. F. C. B. Damiao, Duc N. Tran, Steven V. Ley
Summary: This study reports the rapid synthesis of 2-pyrazolines from aldehydes via [3 + 2] cycloaddition of unstabilised diazo species and mono and di-substituted alkenes. The development includes semi-continuous and fully continuous methods, with a fully automated compound library generation and a graphical interface for automation control.
REACTION CHEMISTRY & ENGINEERING
(2023)
Article
Multidisciplinary Sciences
Torben Rogge, Nikolaos Kaplaneris, Naoto Chatani, Jinwoo Kim, Sukbok Chang, Benudhar Punji, Laurel L. Schafer, Djamaladdin G. Musaev, Joanna Wencel-Delord, Charis A. Roberts, Richmond Sarpong, Zoe E. Wilson, Margaret A. Brimble, Magnus J. Johansson, Lutz Ackermann
Summary: C-H activation has emerged as a powerful platform for molecular syntheses in various fields including natural product syntheses, pharmaceutical industries, and material sciences. This Primer summarizes best practices for experimental set-up, data deposition, and key developments in C-H activation, as well as discussing its applications and limitations.
NATURE REVIEWS METHODS PRIMERS
(2021)
Review
Biochemistry & Molecular Biology
Zoe E. Wilson, Margaret A. Brimble
Summary: Extremophilic and extreme-tolerant microorganisms have been found to be a rich source of novel structures, with a wide variety of new molecules isolated from them since 2009, showcasing a range of reported bioactivities.
NATURAL PRODUCT REPORTS
(2021)
