Concise synthesis and revision of the proposed biogenesis of helicascolides

Abstract A concise synthesis of helicascolides A, B and C was achieved in three to five steps from commercially available materials. The key transformations of the synthesis include an Evans-Metternich anti -aldol reaction of the known β-keto imide 10 and strategic base-mediated one-pot cyclization/alkylation. Based on the new chemical evidence of ring-opening reaction of β-keto ester under biocompatible basic conditions, Krohn’s proposal for the biosynthetic relationship between helicascolide A ( 1 ) and a naturally co-existing acyclic dienone 4 was suggested in a reverse manner.