Total Synthesis of Aculenes B and D

Abstract

AbstractThe first total synthesis of aculene D, a structurally rare nordaucane‐type natural product exhibiting quorum sensing inhibitory activity, has been accomplished from a known five‐membered hydroxy carboxylic acid. Nucleophilic addition of methallylzinc bromide to a β‐keto aldehyde intermediate under Barbier conditions to install the secondary hydroxy group on the seven‐membered ring of aculene D gave the corresponding alcohol with an undesired configuration predominantly. On the other hand, the protection of its keto group as the ethylene acetal induced a reversal of diastereoselectivity, affording a desired diastereomer in a selective manner. The construction of the seven‐membered ring was realized by ring‐closing metathesis using a triethylsilyl‐protected monocyclic diene ester precursor. An additional five‐step manipulation on the cyclization product including the installation of an ethyl group on the five‐membered ring completed the synthesis of aculene D, whose esterification with an N‐protected l‐proline followed by deprotection also achieved the first total synthesis of aculene B.