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Synthesis of the antifungal macrolide antibiotic (+)-roxaticin
David A Evans1, Brian T Connell
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA. Evans@Chemistry.Harvard.edu
Abstract:
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.
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