Total synthesis and chemical stability of pseudouridimycin.
| Autor: | Cain CF; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA. jdelvalle@nd.edu., Scott AM; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA. jdelvalle@nd.edu., Sarnowski MP; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA. jdelvalle@nd.edu., Del Valle JR; Department of Chemistry & Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA. jdelvalle@nd.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Chemical communications (Cambridge, England) [Chem Commun (Camb)] 2022 Feb 15; Vol. 58 (14), pp. 2351-2354. Date of Electronic Publication: 2022 Feb 15. |
| DOI: | 10.1039/d1cc07059b |
| Abstrakt: | We report the chemical synthesis of pseudouridimycin (1), an antimicrobial natural product that potently and selectively inhibits bacterial RNA polymerase. Chemical stability studies revealed intramolecular hydroxamate bond scission to be a major decomposition pathway for 1 in aqueous buffer. Replacement of the hydroxamate bond with a tertiary amide, as in 16, afforded a conformational isostere resistant to degradation. These studies pave the way for the design and synthesis of analogues with improved chemical stability and biological activity. |
| Databáze: | MEDLINE |
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