Article
Chemistry, Multidisciplinary
Chelsea R. Jones, Gretchen Guaglianone, Grant H. Lai, James S. Nowick
Summary: The antibiotic teixobactin shows potential as a candidate drug to combat drug-resistant pathogens, but its gel-like form limits its use in intravenous administration. O-Acyl isopeptide prodrug analogues of teixobactin provide a solution to the gel formation issue while retaining antibiotic activity. These prodrug analogues convert to the corresponding amides in a clean manner and exhibit good antibiotic activity against Gram-positive bacteria.
Article
Multidisciplinary Sciences
Kyan A. D'Angelo, Carly K. Schissel, Bradley L. Pentelute, Mohammad Movassaghi
Summary: The study presents a concise total synthesis method for himastatin, a natural product with an unusual homodimeric structure. The final-stage dimerization strategy used in the synthesis was inspired by a detailed understanding of the compound's biogenesis. By combining this approach with a modular synthesis, a series of designed derivatives of himastatin, including synthetic probes to investigate its antibiotic activity, were efficiently accessed.
Article
Chemistry, Organic
Namdeo Gangathade, Kiranmai Nayani, Hemalatha Bukya, Prathama S. Mainkar, Srivari Chandrasekhar
Summary: A scalable synthesis of L-allo-enduracididine is achieved from commercially available (S)-glycidol in ten linear steps, involving well-established synthetic transformations. The synthetic route is flexible and can synthesize all four diastereomers by changing the stereochemistry of glycidol and Sharpless asymmetric dihydroxylation reagent.
Article
Chemistry, Multidisciplinary
Chi He, Yu Wang, Cheng Bi, David S. Peters, Timothy J. Gallagher, Johannes Teske, Jason S. Chen, Rachel Corsetti, Anthony D'Onofrio, Kim Lewis, Phil S. Baran
Summary: A modular total synthesis method for kibdelomycin has been disclosed, which allows for structure-activity relationship studies. This method uses simple building blocks and addresses lingering questions regarding its structural assignment and its relationship to amycolamicin. Initial antibacterial assays indicate that both C-22 epimers of the natural product exhibit similar activity, while structurally truncated analogs lose activity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Feng-Yuan Wang, Lei Jiao
Summary: An asymmetric total synthesis of cage-like indole alkaloid arborisidine is achieved using a new synthetic strategy that involves a catalytic parallel kinetic resolution based on ambident nucleophilicity of indole and a 5-exo-trig radical cyclization.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Multidisciplinary
Hao Yu, Zachary P. Sercel, Samir P. Rezgui, Jonathan Farhi, Scott C. Virgil, Brian M. Stoltz
Summary: This study describes a synthetic approach to aleutianamine and highlights its potent biological activity against human pancreatic cancer cells, making it a potential candidate for therapeutic development.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Vasil H. Vasilev, Lukas Spessert, Kuan Yu, Thomas J. Maimone
Summary: The large family of daphnane diterpene orthoesters (DDOs) represents a remarkable class of natural products both in terms of structure and function. They are potent lead compounds for the treatment of pain, neurodegeneration, HIV/AIDS, and cancer. However, the synthesis of DDO natural products remains rare.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Chemistry, Multidisciplinary
Yang Wang, Yongjian Su, Yanxing Jia
Summary: In this research, the structurally intriguing diterpene (+)-aberrarone was synthesized in only 12 steps from commercially available (S,S)-carveol without protecting group manipulations. This concise synthesis includes a Cu-catalyzed asymmetric hydroboration to generate the chiral methyl group, a Ni-catalyzed reductive coupling to link two fragments, and a Mn-mediated radical cascade cyclization to construct the triquinane system.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Jiujian Ji, Jiajun Chen, Sixun Qin, Wanye Li, Jun Zhao, Guozhao Li, Hao Song, Xiao-Yu Liu, Yong Qin
Summary: This article reports the first total synthesis of vilmoraconitine using efficient ring-forming reactions. Key steps include an oxidative dearomatization-induced Diels-Alder cycloaddition, a hydrodealkenylative fragmentation/Mannich sequence, and an intramolecular Diels-Alder cycloaddition.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Stephan N. Hess, Xiaobin Mo, Conny Wirtz, Alois Fuerstner
Summary: Limaol, a marine-derived C40-polyketide, is unique in structure due to the nonthermodynamic array of four skipped methylene substituents on its hydrophobic tail. This distinctive segment was assembled using a two-directional approach and coupled to the polyether domain through an allyl/alkenyl Stille reaction under neutral conditions. The core region was prepared through several key steps, including asymmetric propargylation catalyzed by 3,3'-dibromo-BINOL, gold-catalyzed spirocyclization, and substrate-controlled allylation to introduce the southern sector.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Daria E. Kim, Yingchuan Zhu, Shingo Harada, Isaiah Aguilar, Abbigayle E. Cuomo, Minghao Wang, Timothy R. Newhouse
Summary: In this study, we successfully reported the total synthesis of the indole diterpenoid natural product shearilicine for the first time through an 11-step sequence using a generalizable precursor. The target molecule was obtained in an enantiospecific manner using a native chiral auxiliary strategy. The formation of the key carbazole substructure was achieved through a mild intramolecular Heck cyclization, which was promoted by noncovalent substrate-ligand and ligand-ligand interactions revealed by computational study.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Multidisciplinary
Xianhuang Zeng, Dale L. Boger
Summary: The total synthesis of (-)-strempeliopine involves a powerful SmI2-mediated and BF3 center dot OEt2-initiated dearomative transannular radical cyclization onto an indole, resulting in the formation of a quaternary center and the strategic C19-C2 bond in its core structure.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Multidisciplinary Sciences
Rhythm Shukla, Francesca Lavore, Sourav Maity, Maik G. N. Derks, Chelsea R. Jones, Bram J. A. Vermeulen, Adela Melcrova, Michael A. Morris, Lea Marie Becker, Xiaoqi Wang, Raj Kumar, Joao Medeiros-Silva, Roy A. M. van Beekveld, Alexandre M. J. J. Bonvin, Joseph H. Lorent, Moreno Lelli, James S. Nowick, Harold D. MacGillavry, Aaron J. Peoples, Amy L. Spoering, Losee L. Ling, Dallas E. Hughes, Wouter H. Roos, Eefjan Breukink, Kim Lewis, Markus Weingarth
Summary: The mechanism of action of Teixobactin has been revealed, showing that it damages bacterial cell membranes by binding to lipid II. This unique mode of action allows Teixobactin to target bacteria without harming human cells, making it a highly effective antibiotic.
Article
Chemistry, Organic
Sanghyeon Lee, Byung-Gyu Kim, Sujeong Geum, Jiheon Kim, Hee-Yoon Lee
Summary: The first total synthesis of (+/-)-jujuyane was achieved from a (5 + 3) dimerization product of oxidopyrylium ylide, which established the cyclooctanoid core structure with stereochemical bias. Selective functional group modifications of the dimeric structure, followed by strategic functional group manipulations around the eight-membered carbocyclic core, paved the way for the total synthesis of (+/-)-jujuyane and will guide future applications in natural product synthesis using oxidopyrylium dimers.
Article
Chemistry, Organic
Kazutoshi Tomoya, Kazuaki Komiya, Daisuke Nakajima, Nariyoshi Umekubo, Satoshi Yokoshima
Summary: A total synthesis of kopsone was achieved by stereoselective preparation of an acyclic aldehyde with a protected hydroxylamine moiety through Ireland-Claisen rearrangement and intramolecular cycloaddition of an eight-membered cyclic nitrone, forming the 2-azabicyclo[3.3.1]nonane skeleton.
Article
Biochemistry & Molecular Biology
Barbara R. Terlouw, Kai Blin, Jorge C. Navarro-Munoz, Nicole E. Avalon, Marc G. Chevrette, Susan Egbert, Sanghoon Lee, David Meijer, Michael J. J. Recchia, Zachary L. Reitz, Jeffrey A. van Santen, Nelly Selem-Mojica, Thomas Torring, Liana Zaroubi, Mohammad Alanjary, Gajender Aleti, Cesar Aguilar, Suhad A. A. Al-Salihi, Hannah E. Augustijn, J. Abraham Avelar-Rivas, Luis A. Avitia-Dominguez, Francisco Barona-Gomez, Jordan Bernaldo-Aguero, Vincent A. Bielinski, Friederike Biermann, Thomas J. Booth, Victor J. Carrion Bravo, Raquel Castelo-Branco, Fernanda O. Chagas, Pablo Cruz-Morales, Chao Du, Katherine R. Duncan, Athina Gavriilidou, Damien Gayrard, Karina Gutierrez-Garcia, Kristina Haslinger, Eric J. N. Helfrich, Justin J. J. van der Hooft, Afif P. Jati, Edward Kalkreuter, Nikolaos Kalyvas, Kyo B. Kang, Satria Kautsar, Wonyong Kim, Aditya M. Kunjapur, Yong-Xin Li, Geng-Min Lin, Catarina Loureiro, Joris J. R. Louwen, Nico L. L. Louwen, George Lund, Jonathan Parra, Benjamin Philmus, Bita Pourmohsenin, Lotte J. U. Pronk, Adriana Rego, Devasahayam Arokia Balaya Rex, Serina Robinson, L. Rodrigo Rosas-Becerra, Eve T. Roxborough, Michelle A. Schorn, Darren J. Scobie, Kumar Saurabh Singh, Nika Sokolova, Xiaoyu Tang, Daniel Udwary, Aruna Vigneshwari, Kristiina Vind, Sophie P. J. M. Vromans, Valentin Waschulin, Sam E. Williams, Jaclyn M. Winter, Thomas E. Witte, Huali Xie, Dong Yang, Jingwei Yu, Mitja Zdouc, Zheng Zhong, Jerome Collemare, Roger G. Linington, Tilmann Weber, Marnix H. Medema
Summary: With the increasing amount of genomic data, (meta)genome mining plays a critical role in discovering pharmaceutical drugs and other materials. MIBiG is a standardized data format and online database for describing and characterizing biosynthetic gene clusters. MIBiG 3.0 is an update of the database that includes validation, re-annotation, and new entries.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Multidisciplinary Sciences
Nicholas J. J. Morehouse, Trevor N. N. Clark, Emily J. J. McMann, Jeffrey A. A. van Santen, F. P. Jake Haeckl, Christopher A. A. Gray, Roger G. G. Linington
Summary: Spectral matching of MS2 fragmentation spectra has limitations due to instrument differences and limited spectral reference libraries. To overcome this challenge, SNAP-MS uses structural similarity network annotation to assign compound families to molecular networking subnetworks without using experimental or calculated reference spectra. SNAP-MS accurately annotates subnetworks built from both reference spectra and an in-house microbial extract library, and predicts compound families from published molecular networks acquired using different MS instruments.
NATURE COMMUNICATIONS
(2023)
Article
Agriculture, Multidisciplinary
Fengke Lin, Edward J. Kennelly, Roger G. Linington, Chunlin Long
Summary: This study conducted a comprehensive metabolomic and bioactivity evaluation of different plant parts from Garcinia yunnanensis and Garcinia xanthochymus. Differences in metabolite profiles and bioactivity were observed among different plant parts. The seeds and latex of both species exhibited excellent cytotoxic and antibacterial activities, while the roots of G. xanthochymus and the arils of G. yunnanensis showed strong anti-inflammatory effects.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Plant Sciences
Warren S. Vidar, Tim U. H. Baumeister, Lindsay K. . Caesar, Joshua J. Kellogg, Daniel A. Todd, Roger G. Linington, Olav M. Kvalheim, Nadja B. Cech
Summary: Mass spectrometry-based metabolomics is widely used to identify active compounds from natural product mixtures. However, traditional metabolomics approaches do not consider the possibility of interactions between mixture components. This study introduces interaction metabolomics, which includes compound interaction terms (CITs) to analyze the interactions in metabolomics data. The results demonstrate the utility of this approach in accurately identifying synergistic compounds in mixtures.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Plant Sciences
Aswad Khadilkar, Zoie L. Bunch, Jessica Wagoner, Vandana Ravindran, Jessica M. Oda, Warren S. Vidar, Trevor N. Clark, Preston K. Manwill, Daniel A. Todd, Sarah A. Barr, Lauren K. Olinger, Susan L. Fink, Wendy K. Strangman, Roger G. Linington, John B. MacMillan, Nadja B. Cech, Stephen J. Polyak
Summary: Research finds that botanical natural products show potential usefulness against COVID-19. Six botanical species and 173 isolated natural product compounds were tested for their ability to block wild-type SARS-CoV-2 infection. It was discovered that alkaloid compounds like tetrandrine can inhibit SARS-CoV-2 infection, including the delta variant of concern.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Plant Sciences
Nicholas J. J. Morehouse, Andrew J. J. Flewelling, Dennis Y. Y. Liu, Hannah Cavanagh, Roger G. G. Linington, John A. A. Johnson, Christopher A. A. Gray
Summary: Two new lipopeptaibols (tolypocaibols A and B) and a mixed natural product (maximiscin [(P/M)-3)]) were isolated from a fungal endophyte of the marine alga Spongomorpha arcta. The lipopeptaibols were found to have 11 amino acid residues with a valinol C-terminus and a decanoyl acyl chain at the N-terminus. Tolypocaibols A and B showed moderate and selective inhibition against Gram-positive and acid-fast bacterial strains, while maximiscin [(P/M)-3)] showed moderate, broad-spectrum antibiotic activity.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Multidisciplinary Sciences
Tara K. Bartolec, Xabier Vazquez-Campos, Alexander Norman, Clement Luong, Marcus Johnson, Richard J. Payne, Marc R. Wilkins, Joel P. Mackay, Jason K. K. Low
Summary: Significant advances in cryoelectron microscopy have expanded our ability to create structural models of proteins and protein complexes. Cross-linking mass spectrometry (XL-MS) is demonstrated to be a powerful tool for high-throughput experimental assessment of protein structures and interactions. The combination of XL-MS data with AlphaFold2 predictions offers opportunities to explore the structural proteome and interactome in depth.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Chemistry, Organic
Arthur H. Tang, Richard J. Payne
Summary: Gallinamide A, a natural product produced by cyanobacteria, shows potent anti-parasitic activity by inhibiting essential cysteine protease enzymes. It has also been found to possess strong antiviral activity against SARS-CoV-2 by covalently inhibiting the host cysteine protease cathepsin L involved in viral entry. To conduct detailed pre-clinical studies on its potential as a COVID-19 antiviral, a more efficient synthetic route was developed to obtain significant quantities of this natural product. The second generation total synthesis of Gallinamide A described here delivered the compound in a yield of 32% on a 315 mg scale over 16 steps (9 steps in the longest linear sequence).
Article
Multidisciplinary Sciences
Dennis Y. Liu, Laura Phillips, Darryl M. Wilson, Kelly M. Fulton, Susan M. Twine, Alex Wong, Roger G. Linington
Summary: Collateral sensitivity (CS), whereby resistance to one drug is accompanied by increased sensitivity to another, provides new opportunities for antimicrobial drug discovery. In this study, the researchers screened large chemical libraries across 29 drug-resistant E. coli strains and identified multiple CS interactions, including natural products with potent CS activities against cephalosporin-resistant strains. The findings suggest that CS can be used to address the challenges of antimicrobial resistance and the slowing rates of drug discovery.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Xia-Ping Fu, Yizhi Yuan, Ajay Jha, Nikita Levin, Jack Ren, Dimitrios Mamalis, Shabaz Mohammed, Benjamin G. Davis, Andrew M. Giltrap
Summary: Chemical post-translational methods allow editing of proteins without genetic intervention. A light-mediated desulfurative method can generate site-selectively edited proteins with full retention of native stereochemistry from a natural amino acid precursor. This methodology has great potential in exploring protein side-chain diversity and function and constructing useful bioconjugates.
ACS CENTRAL SCIENCE
(2023)
Review
Chemistry, Multidisciplinary
Katriona Harrison, Angus S. Mackay, Lucas Kambanis, Joshua W. C. Maxwell, Richard J. Payne
Summary: The homochirality of biomolecules in nature has been crucial for the existence of life and has also provided opportunities for synthetic chemists to generate molecules with inverted chirality. Recent work on synthetic mirror-image proteins, using modern synthetic strategies, has led to their applications in protein crystallography, drug discovery, and the creation of mirror-image life.
NATURE REVIEWS CHEMISTRY
(2023)
Article
Chemistry, Analytical
Michael J. J. Recchia, Tim U. H. Baumeister, Dennis Y. Y. Liu, Roger G. G. Linington
Summary: The ability to analyze natural product mixtures lags behind the advancements in genome sequencing technologies and laboratory automation, limiting new molecule discovery. However, a new multiplexing strategy has been developed to increase mass spectrometry-based profiling up to 30-fold, allowing for the identification of infrequently occurring metabolites. This method has been successfully validated and applied in a biological activity profiling study, rediscovering all previously reported bioactive metabolites.
ANALYTICAL CHEMISTRY
(2023)
Review
Biotechnology & Applied Microbiology
Michael W. Mullowney, Katherine R. Duncan, Somayah S. Elsayed, Neha Garg, Justin J. J. van der Hooft, Nathaniel I. Martin, David Meijer, Barbara R. Terlouw, Friederike Biermann, Kai Blin, Janani Durairaj, Marina Gorostiola Gonzalez, Eric J. N. Helfrich, Florian Huber, Stefan Leopold-Messer, Kohulan Rajan, Tristan de Rond, Jeffrey A. van Santen, Maria Sorokina, Marcy J. Balunas, Mehdi A. Beniddir, Doris A. van Bergeijk, Laura M. Carroll, Chase M. Clark, Djork-Arne Clevert, Chris A. Dejong, Chao Du, Scarlet Ferrinho, Francesca Grisoni, Albert Hofstetter, Willem Jespers, Olga V. Kalinina, Satria A. Kautsar, Hyunwoo Kim, Tiago F. Leao, Joleen Masschelein, Evan R. Rees, Raphael Reher, Daniel Reker, Philippe Schwaller, Marwin Segler, Michael A. Skinnider, Allison S. Walker, Egon L. Willighagen, Barbara Zdrazil, Nadine Ziemert, Rebecca J. M. Goss, Pierre Guyomard, Andrea Volkamer, William H. Gerwick, Hyun Uk Kim, Rolf Mueller, Gilles P. van Wezel, Gerard J. P. van Westen, Anna K. H. Hirsch, Roger G. Linington, Serina L. Robinson, Marnix H. Medema
Summary: The developments in computational omics technologies in combination with artificial intelligence approaches have opened up new possibilities for drug discovery. However, addressing key challenges such as high-quality datasets and algorithm validation is essential to realize the potential of these synergies.
NATURE REVIEWS DRUG DISCOVERY
(2023)
Article
Multidisciplinary Sciences
Shankar Raj Devkota, Pramod Aryal, Rina Pokhrel, Wanting Jiao, Andrew Perry, Santosh Panjikar, Richard J. Payne, Matthew C. J. Wilce, Ram Prasad Bhusal, Martin J. Stone
Summary: This study focused on a type of chemokine-binding proteins called A3 evasins from tick saliva, which can bind with CC chemokines and inhibit their receptor activation. Structure-based modifications of A3 evasins can alter their chemokine selectivity, suggesting their potential applications in targeted anti-inflammatory therapy.
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Medicinal
Kasuni B. Ekanayake, Mithun C. Mahawaththa, Haocheng Qianzhu, Elwy H. Abdelkader, Josemon George, Sven Ullrich, Rhys B. Murphy, Sarah E. Fry, Jason Johansen-Leete, Richard J. Payne, Christoph Nitsche, Thomas Huber, Gottfried Otting
Summary: TMSK, TMSNK, and TFAK are non-canonical amino acids that can be incorporated into proteins through genetic encoding. A new aminoacyl-tRNA synthetase specific for TMSNK is described, which is chemically more stable. Using the SARS-CoV-2 main protease (Mpro) as a model system, intense signals in the nuclear magnetic resonance (NMR) spectrum were observed for the trimethylsilyl and CF3 groups. The response of these groups to active-site ligands differed depending on their proximity to the active site, and the previously reported binding site of the ligand pelitinib was not confirmed.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
