Author:
Pettit George R.,Singh Sheo Bux
Abstract
Further investigation of the South African tree Combretumcaffrum (Combretaceae) for murine P388 lymphocytic leukemia (PS) cell-growth inhibitory substances has led to discovery of three new active constituents designated combretastatins A-2 (5a, PS ED50 0.027 μg/mL), A-3 (5b, PS ED50 0.026 μg/mL), and B-2 (3b, PS ED50 0.32 μg/mL). Both combretastatins A-2 and A-3 were found to markedly inhibit tubulin polymerization. The structure of each combretastatin was firmly established by a combination of high resolution (400 MHz) 1H and 13C nuclear magnetic resonance and mass spectral analyses followed by total syntheses. The conversion of methyl gallate (7b) to combretastatin A-2 via intermediates 7c → 7d → 7e → 7a and 6a → 5a illustrates the practical synthetic route utilized for obtaining these substances. The Wittig reaction employed as the penultimate step in obtaining combretastatins A-3, afforded predominantly the natural Z isomer.
Publisher
Canadian Science Publishing
Subject
Organic Chemistry,General Chemistry,Catalysis
Cited by
122 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. Discovery, synthesis, activities, structure–activity relationships, and clinical development of combretastatins and analogs as anticancer drugs. A comprehensive review;Natural Product Reports;2024
2. Therapeutic Potential and Predictive Pharmaceutical Modeling of Stilbenes in Cannabis sativa;Pharmaceutics;2023-07-12
3. A review on the secretory structures, bioactive compounds and biological activities of selected Combretum species;South African Journal of Botany;2023-07
4. Silicon switch: Carbon–silicon Bioisosteric replacement as a strategy to modulate the selectivity, physicochemical, and drug‐like properties in anticancer pharmacophores;Chemical Biology & Drug Design;2023-04-07
5. Design, synthesis, and anticancer evaluation of 1-benzo[1,3]dioxol-5-yl-3-N-fused heteroaryl indoles;Molecular Diversity;2023-02-03