Practical Gram-Scale Synthesis of Iboxamycin, a Potent Antibiotic Candidate
| Autor: | Aditya R. Pote, Jeremy D. Mason, Daniel W. Terwilliger, Andrew G. Myers |
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| Rok vydání: | 2021 |
| Předmět: |
Models
Molecular Bicyclic molecule Negishi coupling Molecular Conformation Stereoisomerism General Chemistry Alkylation Crystallography X-Ray Ring (chemistry) Biochemistry Combinatorial chemistry Catalysis Anti-Bacterial Agents Stereocenter Oxepane chemistry.chemical_compound Colloid and Surface Chemistry chemistry Intramolecular force Amide Oxepins Pyrans |
| Zdroj: | Journal of the American Chemical Society. 143:11019-11025 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.1c03529 |
| Popis: | A gram-scale synthesis of iboxamycin, an antibiotic candidate bearing a fused bicyclic amino acid residue, is presented. A pivotal transformation in the route involves an intramolecular hydrosilylation-oxidation sequence to set the ring-fusion stereocenters of the bicyclic scaffold. Other notable features of the synthesis include a high-yielding, highly diastereoselective alkylation of a pseudoephenamine amide, a convergent sp3-sp2 Negishi coupling, and a one-pot transacetalization-reduction reaction to form the target compound's oxepane ring. Implementation of this synthetic strategy has provided ample quantities of iboxamycin to allow for its in vivo profiling in murine models of infection. |
| Databáze: | OpenAIRE |
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