Synthesis of the originally proposed structure of palmerolide C

• Main Author: Wlochal, Joanna
• Other Authors: Florence, Gordon John, Engineering and Physical Sciences Research Council (EPSRC)
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: University of St Andrews 2013
• Subjects: RM666.M25W6; Macrolide antibiotics > Synthesis; Antarctic; The Antarctic; Antarc*
• Online Access: http://hdl.handle.net/10023/3663

The palmerolides are an emerging class of polyketide natural products isolated from marine organisms inhabiting the Antarctic Sea. Although there has been a substantial effort to prepare the most active family member palmerolide A, no synthetic work has been performed in the area of the other members of the family; palmerolides B and C of different ring structure. These compounds are particularly interesting due to their complex structures with undefined stereochemistry and both display high selectivity towards human melanoma cancer cell lines. A highly convergent strategy to access palmerolide C has been developed, relying on the assembly of three fragments using key bond couplings at C6-C7 (boron-mediated aldol reaction/dehydration) and C14-C15 (Julia-Kocienski olefination), followed by a suitable macrolactonisation step and Buchwald enamide formation. Prior to subunit synthesis, the relative configuration of the C8-C10 stereotriad was resolved via the synthesis of diastereomeric degradation fragments by the application of organocatalytic cross aldol reactions and a suitable 1,3-selective reduction.