Total Synthesis of Aigialomycin D Using a Ramberg−Bäcklund/RCM Strategy

The bioactive resorcylic acid lactone aigialomycin D (1) has been synthesized by a novel combination of ring-closing metathesis (RCM) and Ramberg−Bäcklund reactions. This synthetic strategy enables the C1′−C2′ alkene to be masked as a sulfone during formation of the macrocycle by ring closing metathesis at the C7′−C8′ olefin, thus avoiding competing formation of a cyclohexene. A subsequent Ramberg−Bäcklund reaction efficiently produces the C1′−C2′ E-alkene. This combined RCM/Ramberg−Bäcklund reaction strategy should be widely applicable to the synthesis of macrocyclic dienes