The 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.
|ジャーナル||European Journal of Organic Chemistry|
|出版ステータス||Published - 2023 2月 6|
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