Institution: | 1. Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza-Aoba, Aoba-ku, Sendai, 980-8572 Japan
Contribution: Investigation (lead);2. Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza-Aoba, Aoba-ku, Sendai, 980-8572 Japan;3. Graduate School of Agricultural Science, Tohoku University, 468-1 Aramaki Aza-Aoba, Aoba-ku, Sendai, 980-8572 Japan
Contribution: Investigation (supporting) |
Abstract: | 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. |