Synthetic studies on gambieric acids, potent antifungal polycyclic ether natural products: Reassignment of the absolute configuration of the nonacyclic polyether core by NMR analysis of model compounds

(Chemical Equation Presented) A highly stereocontrolled, convergent synthesis of the A/B-ring fragment of gambieric acids (GAs) has been developed on the basis of (i) a Suzuki-Miyaura coupling of the C1-C6 alkylborate and the C7-C17 vinyl iodide and (ii) a diastereoselective haloetherification for the construction of the A-ring tetrahydrofuran as key steps. Inspection of the ¹H and ¹³C NMR chemical shifts of the synthesized A/B-ring model compounds led to a stereochemical reassignment of the absolute configuration of the polycyclic ether core of GAs. This structure revision was further supported by a synthesis of the A/BC-ring model compound of gambieric acid B and a comparison of its ¹H and ¹³C NMR data with those of the natural product.