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Covering: 2013 to 2024Cycloaddition reactions, which efficiently construct polycyclic ring systems and stereocenters, are powerful tools in the total synthesis of natural products. Given the significant progress and numerous elegant applications of [5 + 2] cycloaddition reactions over the past decade, this review systematically summarizes the advances in three major types of [5 + 2] cycloaddition reactions in natural product synthesis from 2013 to 2024. The advantages of [5 + 2] cycloadditions in constructing complex natural product frameworks are illustrated through comparisons with alternative strategies for the same targets. Additionally, trends and future prospects for [5 + 2] cycloadditions are discussed, offering valuable insights for further research and broader applications.
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http://dx.doi.org/10.1039/d5np00023h | DOI Listing |
J Am Chem Soc
September 2025
Center of Drug Discovery, State Key Laboratory of Natural Medicine, China Pharmaceutical University, Nanjing 211198, China.
The advancement of bioorthogonal cleavage platforms has emerged as a critical frontier in chemical biology, offering precise molecular liberation through physiologically compatible activation mechanisms. Despite its significant potential, ensuring efficacy typically requires rapid reaction kinetics, high-efficiency payload release, and stable reactants; however, relevant reports remain sparse. Herein, we developed a strain-promoted alkyne-nitrone cycloaddition (SPANC)-based click-release chemistry through installation of a carbamate-linked release moiety at the propargyl position of cyclooctyne, triggering a spontaneous elimination following click cycloaddition to achieve efficient payload liberation.
View Article and Find Full Text PDFBeilstein J Nanotechnol
August 2025
Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montreal, QC H3A 0B8, Canada.
The preparation of multimodal nanoparticles by capping magnetic iron oxide nanoparticles (IONPs) with functional organic molecules is a major area of research for biomedical applications. Conjugation reactions, such as carbodiimide coupling and the highly selective class of reactions known as "click chemistry", have been instrumental in tailoring the ligand layers of IONPs to produce functional biomedical nanomaterials. However, few studies report the controls performed to determine if the loading of molecules onto IONPs is due to the proposed coupling reaction(s) employed, or some other unknown interaction with the IONP surface.
View Article and Find Full Text PDFRSC Adv
September 2025
Process and Environmental Engineering Laboratory (LIPE), Faculty of Chemistry, University of Science and Technology of Oran Mohamed Boudiaf P. O. Box 1503, El Mnaouer 31000 Oran Algeria.
In this contribution, Molecular Electron Density Theory (MEDT) is employed to investigate the (3 + 2) cycloaddition reaction between ()--methyl--(2-furyl)-nitrone 1 and but-2-ynedioic acid 2. DFT calculations at the M06-2X-D3/6-311+G(d,p) level of theory under solvent-free conditions at room temperature show that this reaction proceeds CA3-Z diastereoselectivity, with the formation of the CA3-Z cycloadduct being both thermodynamically and kinetically more favoured than the CA4-Z one. Reactivity parameters obtained from CDFT calculations reveal that compound 1 predominantly behaves as a nucleophile with moderate electrophilic features, in contrast to compound 2, which demonstrates strong electrophilicity and limited nucleophilic ability.
View Article and Find Full Text PDFJ Org Chem
September 2025
Department of Chemistry, University of Rochester, 120 Trustee Road, Rochester, New York 14627, United States.
This report presents the alkynyl -Prins cyclization of Achmatowicz adducts, enabling the synthesis of up to 24 (24) highly functionalized [4.3.1] and [3.
View Article and Find Full Text PDFInorg Chem
September 2025
Department of Chemistry, Panskura Banamali College, Panskura RS, Purba Medinipur, WB 721152, India.
We report the synthesis and characterization of a new Schiff base ligand (HL), derived from 2-picolylamine and 2-hydroxy-3-methoxy-5-methylbenzaldehyde. Its reaction with Ni(NO)·6HO and Ln(NO)·HO (Ln = Gd, Tb, Dy) in the presence of triethylamine affords a carbonato-bridged family of heterobimetallic NiLn complexes: [NiLn(L)(L')(μ-CO)(NO)]·MeOH·HO (). During the complexation reaction, ligand HL undergoes an oxidation, followed by C-C coupling to generate a secondary ligand (HL').
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