Synthesis of the antifungal macrolide antibiotic (+)-roxaticin.
The total synthesis of the antifungal macrolide antibiotic roxaticin has been accomplished. The synthesis relies principally on aldol and directed reduction steps to construct the extended 1,3-polyol array present in the natural product. Three principal nonpolyene containing fragments were assembled and then coupled using Julia olefination and methyl ketone aldol addition reactions. A series of functionalization reactions incorporated the sensitive polyene and provided the protected roxaticin seco-acid, which was lactonized in good yield. Acidic deprotection completed this convergent synthesis of roxaticin.
Evans
David A
DA
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. Evans@Chemistry.Harvard.edu
Connell
Brian T
BT
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D018942:Macrolides; C480363:roxaticin