Article
Chemistry, Multidisciplinary
Wei Fu, Valentina Pelliccioli, Moritz von Geyso, Pablo Redero, Christian Boehmer, Martin Simon, Christopher Golz, Manuel Alcarazo
Summary: A series of helically shaped benzo[b]chryseno[4,3-d]thiophenes, naphtho[1,2-b]phenanthro[4,3-d]thiophenes, and chryseno[3,4-b]naphtho[1,2-d]thiophenes are synthesized via an enantioselective Au-catalyzed intramolecular alkyne hydroarylation reaction. The inversion barriers and chiroptical properties of the obtained structures are determined. Preliminary studies on the post-synthetic functionalization and transformation into azahelicenes are also presented. Furthermore, a one-step protocol is developed to convert the initially obtained chryseno[3,4-b]naphtho[1,2-d]thiophenes into pleiadene derivatives without erosion of the enantiopurity, enabling the establishment of correlations between structure and conformational stability or (chir)optical properties.
ADVANCED MATERIALS
(2023)
Article
Chemistry, Multidisciplinary
Gustav J. Wormer, Nikolaj L. Villadsen, Peter Norby, Thomas B. Poulsen
Summary: The highly concise asymmetric synthesis of Streptazone A and abikoviromycin was reported in this study, which involved a series of catalytic reactions. Unexpected transformations of streptazone A towards a cysteine mimic, N-acetylcysteamine, were discovered, including the formation of bis-thiol conjugation. The research provides a flexible access to these compounds for further studies on their direct biological targets.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Kazuto Suzuki, Joshua Kyle Stanfield, Keita Omura, Yuma Shisaka, Shinya Ariyasu, Chie Kasai, Yuichiro Aiba, Hiroshi Sugimoto, Osami Shoji
Summary: Catching the structure of cytochrome P450 enzymes in flagrante is crucial for the development of P450 biocatalysts. We report the crystal structure of P450BM3 mimicking the state in the precise moment preceding epoxidation, which is in perfect agreement with the experimentally observed stereoselectivity. This method serves as a powerful tool for predicting and modelling the stereoselectivity of P450 reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Applied
Yuan-Ting Cho, Avijit K. Adak, Yung-Yu Su, Ting-Wei Chang, Chun-Cheng Lin
Summary: In this study, a chemoenzymatic synthesis of the trisialoganglioside LLG-5 1 was accomplished, exhibiting neuritogenic activity. A photoactivatable lactosyl phytosphingosine was developed to enable solubility in enzymatic reactions. This synthetic strategy may be applicable for the synthesis of other gangliosides.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Physical
Jian Zhang, Mingyang Song, Weijun Tang, Dong Xue, Jianliang Xiao, Huaming Sun, Chao Wang
Summary: Converting racemic compounds to enantioenriched products is a common method in accessing chiral molecules. In this study, a kinetic resolution method is used to transform racemic allylic alcohols into chiral compounds, with good yields and stereoselectivities.
Review
Chemistry, Organic
Zlata Boiarska, Tommaso Braga, Alessandra Silvani, Daniele Passarella
Summary: Asymmetric allylation is an important reaction in natural product synthesis, allowing for the preparation of versatile chiral building blocks. Brown allylation has been successfully applied in the synthesis of various natural products, including macrolides and alkaloids.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Jin Cui, Raphael Oriez, Hidetoshi Noda, Takumi Watanabe, Masakatsu Shibasaki
Summary: The copper(I)-catalyzed asymmetric vinylogous additions of siloxyfurans to 2-ester-substituted chromones enable concise and enantioselective assembly of chromanone lactones. This method provides a efficient synthesis of chromanone lactones with precise stereochemical control, which can be used for the formal synthesis of secalonic acid A.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Chemistry, Organic
Soumik De, Aritra Kumar Dan, Raghaba Sahu, Debadutta Das
Summary: This review focuses on the role and mechanisms of various catalysts in synthesizing halocyclized products, highlighting the enantioselectivities, diastereoselectivities, and regioselectivities studied in existing literature.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Plant Sciences
Gopalsamy Rajiv Gandhi, Poovathumkal James Antony, Maria Julia Miranda de Paula Lana, Brenda Fernandes Xavier da Silva, Roberta Vieira Oliveira, Gnanasekaran Jothi, Govindasamy Hariharan, Thiruchenduran Mohana, Ren-You Gan, Ricardo Queiroz Gurgel, Rosana Cipolotti, Lucindo Jose Quintana Junior
Summary: This study systematically reviewed the potential of natural products in regulating cancer-related signaling pathways, showing their ability to weaken pro-and anti-inflammatory signaling markers. Flavonoids, polyphenols, polysaccharides, alkaloids, and tannins are believed to play important roles in cancer modulation.
Review
Pharmacology & Pharmacy
Lulu Gao, Xudong Liu, Xiaoyan Luo, Xiaofan Lou, Pusen Li, Xian Li, Xiaomeng Liu
Summary: Aging is influenced by various factors and has led to an increase in aging-related diseases globally. Natural products have been used for a long time and have been proven to have antiaging effects through various cellular pathways. This article reviews several natural products with potential antiaging properties and highlights their cellular and molecular mechanisms.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Chemistry, Medicinal
Fan Zhang, Tao Zeng, Ruibo Wu
Summary: Natural products and their derivatives are widely used in various industries, especially pharmaceuticals. Modern engineered biosynthesis offers an alternative approach for producing diverse natural products. However, natural enzymes often exhibit unsatisfactory catalytic characteristics and require further enzyme engineering modifications. QM/MM, a computational tool extensively used in enzyme catalysis, has been increasingly applied in rational enzyme engineering for natural product biosynthesis. This review summarizes recent advances in QM/MM computational investigation on enzyme catalysis and enzyme engineering and discusses the challenges and perspectives for future QM/MM-assisted enzyme engineering in natural product biosynthesis.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2023)
Article
Chemistry, Organic
Ting-Yu Lu, Wan-Yun Hsu, Bo-Wei Huang, Jeng-Liang Han
Summary: Two reagent-controlled regiodivergent annulation protocols were developed for the synthesis of bicyclic cyclopenta[b]pyrans and 8-oxabicyclo[3.2.1]octane derivatives with vinylogous nucleophiles.
Article
Chemistry, Multidisciplinary
Arnau Rodriguez-Rubio, Andrea Savoini, Florian Modicom, Patrick Butler, Stephen M. Goldup
Summary: This study presents a synthetic method for producing highly enantioenriched catenanes and explores a neglected topologically chiral stereogenic unit arising from the desymmetrization of a bilaterally symmetric ring.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Physical
Jian-Hua Liu, Qing Zhou, Yao Lin, Zhu-Lian Wu, Tian Cai, Wei Wen, Yan-Min Huang, Qi-Xiang Guo
Summary: In this study, a highly efficient atom-economic asymmetric alpha-allylation method using chiral-aldehyde/palladium catalyst was reported. This method enables the asymmetric alpha-allylation of different 1,3-dienes and allenes with N-unprotected amino acid esters, leading to the synthesis of alpha,alpha-disubstituted chiral alpha-amino acid esters with high efficiency, good yields, and stereoselectivities. No N-allylation byproducts were observed in these reactions. Two reaction models were proposed based on mechanistic control experiments. Overall, this work demonstrates a new approach for preparing structurally diverse chiral amino acids and provides insights for developing chiral-aldehyde catalytic systems.
Article
Chemistry, Multidisciplinary
Wei Ding, Javier Remon, Zhicheng Jiang
Summary: This study presents a novel 'Two Birds with One Stone' strategy to eliminate Cr and colorant pollutions in leather tanning. By using a Cr-free tanning agent with in situ dyeing ability, the researchers successfully produced tanned leather with sufficient thermal stability and desirable brown color. The leather produced through this method exhibited excellent dyeing uniformity, color fastness, and mechanical strength.
Article
Biochemistry & Molecular Biology
Hiromasa Yoshioka, Tatsuro Kawamura, Makoto Muroi, Yasumitsu Kondoh, Kaori Honda, Makoto Kawatani, Harumi Aono, Herbert Waldmann, Nobumoto Watanabe, Hiroyuki Osada
Summary: The compound NPD4928 was identified to enhance the sensitivity of various cancer cells to GPX4 inhibitors, potentially having therapeutic potential via the induction of ferroptosis.
ACS CHEMICAL BIOLOGY
(2022)
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
Chemistry, Multidisciplinary
Saad Shaaban, Christian Merten, Herbert Waldmann
Summary: Axially chiral atropisomeric compounds, especially indole- and indoline-based frameworks, are important heterobiaryl classes widely applied in asymmetric catalysis and medicinal chemistry. The synthesis of C7-substituted indole biaryls and the analogous indoline derivatives is particularly challenging, and efficient methods for their synthesis are in high demand. Transition-metal catalysis is considered one of the most efficient methods for constructing atropisomers.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Medicinal
Fabian Wesseler, Daniel Riege, Mahesh Puthanveedu, Jonas Halver, Eva Mueller, Jessica Bertrand, Andrey P. Antonchick, Sonja Sievers, Herbert Waldmann, Dennis Schade
Summary: We report on the feasibility of using embryonic development in vitro to identify small-molecule cytokine mimetics and signaling activators. A target-agnostic high-throughput assay was used to probe BMP signaling during the patterning of embryonic stem cells. Through a chemical screen and hit validation, 2,3-disubstituted 4H-chromen-4-ones were identified as potent BMP potentiators with osteogenic efficacy. These findings provide novel chemical probes for (stem) cell biology, regenerative medicine, and basic research on the BMP pathway.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Michael Grigalunas, Susanne Brakmann, Herbert Waldmann
Summary: This article introduces the concept, design, and development workflow of pseudo-natural products, and discusses their relationship with natural products and cheminformatic analysis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Cell Biology
Rene Guenther, Arun Pal, Chloe Williams, Vitaly L. Zimyanin, Maria Liehr, Clare von Neubeck, Mechthild Krause, Mrudula G. Parab, Susanne Petri, Norman Kalmbach, Stefan L. Marklund, Jared Sterneckert, Peter Munch Andersen, Florian Wegner, Jonathan D. Gilthorpe, Andreas Hermann
Summary: Little is known about the early pathogenic events of mutant SOD1 in ALS. Using a human iPSC model, this study reveals that mitochondrial dysfunction is one of the crucial early steps in the pathogenic cascade of SOD1-ALS.
Article
Chemistry, Multidisciplinary
Michael Grigalunas, Sohan Patil, Adrian Krzyzanowski, Axel Pahl, Jana Flegel, Beate Schoelermann, Jianing Xie, Sonja Sievers, Slava Ziegler, Herbert Waldmann
Summary: Pseudo-natural products (pseudo-NPs) are novel bioactive compounds that are formed by combining fragments of natural product (NP) in new ways. Previously, pseudo-NPs were created by combining fragments from unrelated NPs, but this study shows that combining fragments from related NPs can also lead to novel chemotypes with unique bioactivity.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Biochemistry & Molecular Biology
Caitlin M. MacCarthy, Jan Huertas, Claudia Ortmeier, Hermann vom Bruch, Daisylyn Senna Tana, Deike Reinke, Astrid Sander, Tim Bergbrede, Ralf Jauch, Hans R. Schoeler, Vlad Cojocaru
Summary: Through experiments and molecular simulations, this study reveals how the pioneer factor Oct4 interprets and enhances nucleosome structural flexibility. Oct4 uses its DNA binding domains to propagate and stabilize open nucleosome conformations, providing a structural basis for the versatility of transcription factors' interaction with nucleosomes.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Medicinal
Adrian Krzyzanowski, Lea Marie Esser, Anthony Willaume, Renaud Prudent, Christoph Peter, Peter't Hart, Herbert Waldmann
Summary: The PRMT5-MEP50 methyltransferase is a major target for the development of anticancer drugs. Researchers have designed and synthesized a new peptide compound that specifically inhibits the interaction between PRMT5 and adaptor proteins RioK1 and pICln. This new inhibitor has great potential for further biological investigations.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Cell Biology
Vitaly L. Zimyanin, Anna-Maria Pielka, Hannes Glass, Julia Japtok, Dajana Grossmann, Melanie Martin, Andreas Deussen, Barbara Szewczyk, Chris Deppmann, Eli Zunder, Peter M. Andersen, Tobias M. Boeckers, Jared Sterneckert, Stefanie Redemann, Alexander Storch, Andreas Hermann
Article
Cell Biology
Bita Massih, Alexander Veh, Maren Schenke, Simon Mungwa, Bettina Seeger, Bhuvaneish T. Selvaraj, Siddharthan Chandran, Peter Reinhardt, Jared Sterneckert, Andreas Hermann, Michael Sendtner, Patrick Lueningschroer
Summary: This article introduces a human neuromuscular co-culture system that enables the formation of neuromuscular junctions by differentiating induced pluripotent stem cells into motor neurons and 3D skeletal muscle tissue. The system is suitable for modeling the pathophysiology of motor neuron diseases and has been used to study the synaptic coupling and muscle contraction in Amyotrophic Lateral Sclerosis (ALS). This in vitro model recapitulates aspects of human physiology and is of great importance for studying human motor neurons in health and disease.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Chemistry, Organic
Sarah Zinken, Axel Pahl, Michael Grigalunas, Herbert Waldmann
Summary: Chromaline pseudo-natural products are a collection of topologically diverse compounds that were designed to access novel biological space by combining chromane and 4H-quinoline natural product fragments. The compounds possess both drug-like and natural product-like properties and have distinct bioactivity profiles compared to previous pseudo-natural product collections. This suggests that the new fragment combination may have led to a unique bioactivity.
Article
Cell Biology
Cristina Marisol Castillo Bautista, Kristin Eismann, Marc Gentzel, Silvia Pelucchi, Jerome Mertens, Hannah E. Walters, Maximina H. Yun, Jared Sterneckert
Summary: Aging disrupts protein homeostasis and contributes to various diseases, including ALS. Repressing autophagy is a strategy to restore protein homeostasis and protect neurons. A study found that obatoclax, a small molecule BH3 mimetic, can disrupt the interaction between BECN1 and BCL2, reducing FUS levels and improving protein homeostasis to rescue neurons. Obatoclax has potential as a therapeutic for ALS and other age-related disorders linked to protein homeostasis defects.
Article
Cell Biology
Francesco Antoniani, Marco Cimino, Laura Mediani, Jonathan Vinet, Enza M. Verde, Valentina Secco, Alfred Yamoah, Priyanka Tripathi, Eleonora Aronica, Maria E. Cicardi, Davide Trotti, Jared Sterneckert, Anand Goswami, Serena Carra
Summary: Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are neurodegenerative disorders linked by genetic causes, with TARDBP, FUS, and C9orf72 genes playing critical roles. The proteins produced by these genes accumulate in the cytoplasm, leading to pathological inclusions. This study explores the connection between the cytoplasmic and nuclear protein quality control (PQC) systems, highlighting the impairment of PML nuclear bodies (PML-NBs) and cytoplasmic stress granules (SGs) in ALS-FTD cases, which contribute to protein aggregation.
CELL DEATH DISCOVERY
(2023)
Review
Chemistry, Multidisciplinary
Daniel J. Foley, Herbert Waldmann
Summary: Natural product-inspired compound collections are important sources for discovering new bioactive compounds for treating diseases. Ketones, with their variety of synthetic transformations, prevalence as commercial building blocks, and relative ease of synthesis, can be valuable as starting materials for the synthesis of natural product-inspired compounds. This review explores the use of ketones as general precursors and summarizes the synthetic transformations available for the annulation of natural product ring-systems to ketone starting materials.
CHEMICAL SOCIETY REVIEWS
(2022)
