Herein, a practical three-component [2 + 1 + 3] cyclization of various cyclic ketones with α,β-unsaturated aldehydes/ketones and ammonium iodide (NHI) to access highly functional fused pyridines has been developed. The features of this transformation include mild reaction conditions, readily available starting materials, and excellent chemoselectivity. This protocol is compatible with various functional groups, and the preliminary studies on the mechanism of the reaction are also provided.
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http://dx.doi.org/10.1021/acs.orglett.4c02628 | DOI Listing |
bioRxiv
December 2024
Rutherford Appleton Laboratory, Research Complex at Harwell, Didcot, Oxfordshire, UK.
Conjugation, the major driver of the spread of antimicrobial resistance genes, relies on a conjugation pilus for DNA transfer. Conjugative pili, such as the F-pilus, are dynamic tubular structures, composed of a polymerized pilin, that mediate the initial donor-recipient interactions, a process known as mating pair formation (MPF). IncH are low-copy-number plasmids, traditionally considered broad host range, which are found in bacteria infecting both humans and animals.
View Article and Find Full Text PDFJ Org Chem
January 2025
Department of Medical Chemistry, Faculty of Chemistry, Adam Mickiewicz University, Uniwersytetu Poznańskiego 8, 61-614 Poznań, Poland.
There has been a long search for a simple preparation of new cyclic analogues of ionophore antibiotics. We report a simple and general synthesis of three new cyclic derivatives of polyether ionophore, monensin A (MON). The application of the Huisgen 1,3-dipolar cycloaddition of azides and terminal alkynes to macrocyclization results in a concise, synthetic route to monensin lacton or lactam in only 4 steps.
View Article and Find Full Text PDFOrg Lett
January 2025
Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
The cyclic structure of non-ribosomal peptides (NRPs) is critical for enhancing their stability and bioactivity, which highlights the importance of exploring NRP cyclization enzymes for natural product discovery. Thioesterases (TEs) are crucial enzymes that catalyze the formation of various lactams, including macrolactams, β-lactams, and γ-lactams; however, their potential to produce other lactam types remains largely unexplored. In this study, we identified spinactin A () and novel derivatives, spinactin B-E (-), from NRRL 18395 and characterized the biosynthetic enzymes involved, particularly a unique TE SncF, responsible for δ-lactam formation.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Department of Chemistry, Northwestern University, Technological Institute, Evanston, Illinois 60208, United States.
Recent advances in redox flow batteries have made them a viable option for grid-scale energy storage, however they exhibit low energy density. One way to boost energy density is by increasing the cell potential using a nonaqueous system. Molecular engineering has proven to be an effective strategy to develop redox-active compounds with extreme potentials but these are usually challenged by resource sustainability of the newly developed redox materials.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Interdisciplinary Life Sciences, The University of Texas at Austin, Austin, Texas 78712, United States.
Language modeling applied to biological data has significantly advanced the prediction of membrane penetration for small-molecule drugs and natural peptides. However, accurately predicting membrane diffusion for peptides with pharmacologically relevant modifications remains a substantial challenge. Here, we introduce PeptideCLM, a peptide-focused chemical language model capable of encoding peptides with chemical modifications, unnatural or noncanonical amino acids, and cyclizations.
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