A general strategy for diversifying complex natural products to polycyclic scaffolds with medium-sized rings
| العنوان: | A general strategy for diversifying complex natural products to polycyclic scaffolds with medium-sized rings |
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| المؤلفون: | Ilia A. Guizei, Stephanie A. Blaszczyk, Scott A. Wildman, Weiping Tang, Zhengqing Ye, Changgui Zhao, Lihong Hu, Zhi-Xiong Ma |
| المصدر: | Nature Communications, Vol 10, Iss 1, Pp 1-10 (2019) Nature Communications |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Alkylation, Science, Drug Evaluation, Preclinical, General Physics and Astronomy, 02 engineering and technology, Imides, Article, General Biochemistry, Genetics and Molecular Biology, Natural (archaeology), Combinatorial libraries, Small Molecule Libraries, 03 medical and health sciences, Drug Discovery, Humans, lcsh:Science, Biological Products, Multidisciplinary, Molecular Structure, Chemistry, Cheminformatics, Oxidation reduction, General Chemistry, Chemical Engineering, 021001 nanoscience & nanotechnology, Combinatorial chemistry, Small molecule, Chemical space, 030104 developmental biology, lcsh:Q, Natural product synthesis, 0210 nano-technology, Diversity-oriented synthesis, Oxidation-Reduction |
| الوصف: | The interrogation of complex biological pathways demands diverse small molecule tool compounds, which can often lead to important therapeutics for the treatment of human diseases. Since natural products are the most valuable source for the discovery of therapeutics, the derivatization of natural products has been extensively investigated to generate molecules for biological screenings. However, most previous approaches only modified a limited number of functional groups, which resulted in a limited number of skeleta. Here we show a general strategy for the preparation of a library of complex small molecules by combining state-of-the-art chemistry – the site-selective oxidation of C-H bonds - with reactions that expand rigid, small rings in polycyclic steroids to medium-sized rings. This library occupies a unique chemical space compared to selected diverse reference compounds. The diversification strategy developed herein for steroids can also be expanded to other types of natural products. Derivatization of natural products is a powerful approach to generate new molecules for biological screenings. Here, the authors employ C-H oxidation and ring expansion methods for the preparation of a library of medium-sized ring skeleta, which occupy a unique chemical space based on chemoinformatic analysis. |
| تدمد: | 2041-1723 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::208158fc2fea22c4543690f0dec0a487 https://doi.org/10.1038/s41467-019-11976-2 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....208158fc2fea22c4543690f0dec0a487 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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