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.
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 (1)H and (13)C 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 (1)H and (13)C NMR data with those of the natural product.
Fuwa
Haruhiko
H
Laboratory of Biostructural Chemistry, Graduate School of Life Sciences, Tohoku University, 1-1 Tsutsumidori-amamiya, Aoba-ku, Sendai 981-8555, Japan. hfuwa@bios.tohoku.ac.jp
Ishigai
Kazuya
K
Goto
Tomomi
T
Suzuki
Akihiro
A
Sasaki
Makoto
M
D000935:Antifungal Agents / Q000737:chemistry*; D001688:Biological Products; D002922:Ciguatoxins / Q000737:chemistry*; D004988:Ethers, Cyclic / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015394:Molecular Structure; D013237:Stereoisomerism
D000935:Antifungal Agents; D001688:Biological Products; D004988:Ethers, Cyclic; D005663:Furans; C521443:gambieric acid C; D002922:Ciguatoxins; C080898:gambieric acid A; C080900:gambieric acid B; C018674:tetrahydrofuran