First Enantioselective Synthesis of Marine Diterpene Ambliol‐A

The first enantioselective synthesis of furanditerpene ambliol‐A, which is a major metabolite of marine sponge Dysidea amblia, has been accomplished by starting from racemic α‐ionone. The key steps of the synthesis include lipase‐mediated resolution of 4‐hydroxy‐γ‐ionone, its stereoselective transformation into trans‐α‐epoxy‐dihydroionone, C2 homologation to trans‐α‐epoxy‐monocyclofarnesyl acetate and Li2CuCl4‐catalysed sp3–sp3 cross‐coupling reaction of the latter ester with (furan‐3‐ylmethyl)magnesium chloride. This work confirms the chemical structure previously assigned to ambliol‐A and proves that the natural levorotatory isomer does not possess (1S,2S) absolute configuration, as previously indicated, but is the opposite enantiomer, (1R,2R)‐2‐[(E)‐6‐(furan‐3‐yl)‐3‐methylhex‐3‐enyl]‐1,3,3‐trimethylcyclohexanol.