A unified strategy for enantioselective total synthesis of cladiellin and briarellin diterpenes: total synthesis of briarellins E and F and the putative structure of alcyonin and revision of its structure assignment.
Enantioselective total syntheses of briarellin E (12) and briarellin F (13), as well as the structure originally proposed for the cladiellin diterpene alcyonin (10), have been realized. Comparison of the spectral data for synthetic 10, natural alcyonin, cladiellisin (33), and cladiellaperoxide (34), as well as chemical transformations of 10 and natural alcyonin, suggest that the structure of this coral metabolite is allylic peroxide 11. The unified approach detailed herein can be used to access both C4-deoxygenated and C4-oxygenated cladiellins and briarellins. The central step in these syntheses is acid-promoted condensation of (Z)-alpha,beta-unsaturated aldehydes 17 with cyclohexadienyl diols 18 to form intermediates 16 incorporating the hexahydroisobenzofuran core and five stereocenters of these marine diterpenes (Scheme 1 ).
Corminboeuf
Olivier
O
Department of Chemistry, 1102 Natural Sciences II, University of California, Irvine, California 92697-2025, USA.
Overman
Larry E
LE
Pennington
Lewis D
LD
D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry*; D004988:Ethers, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism; D013256:Steroids / Q000737:chemistry*
D004224:Diterpenes; D004988:Ethers, Cyclic; D013256:Steroids; C476170:alcyonin; C475784:briarellin E; C475783:briarellin F; C506145:cladiellin A