A unified approach to polyene macrolides: synthesis of candidin and nystatin polyols.
Polyene macrolide antibiotics are naturally occurring antifungal agents. Members of this class include amphotericin B, which has been used widely to treat systemic fungal infections. A general synthetic strategy has been devised to prepare polyol chains associated with the polyene macrolides. Cyanohydrin acetonide alkylations were used to assemble the carbon skeleton, and a simple modification of the strategy allowed an advanced intermediate to be converted to either the candidin polyol or the nystatin polyol. The candidin polyol was further elaborated to a protected candidin aglycone. This strategy will be applicable to other members of the polyene macrolide natural products.
Kadota
Isao
I
Department of Chemistry, University of California, Irvine, CA 92697-2025, USA.
Hu
Yueqing
Y
Packard
Garrick K
GK
Rychnovsky
Scott D
SD
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009761:Nystatin / Q000138:chemical synthesis* / Q000737:chemistry; D011090:Polyenes / Q000138:chemical synthesis / Q000737:chemistry
D000935:Antifungal Agents; D018942:Macrolides; D011090:Polyenes; D009761:Nystatin; C010428:candidin