A Straightforward Synthesis of a Diene From a Homoallylic Bromide to Access Cycloadducts to Elucidate Michael Acceptors as Antimicrobial Motifs

ABSTRACT

Conjugated dienes are useful precursors to cascade reactions that undergo cycloadditions to access polycyclic compounds toward bioactive natural products. However, the synthesis of the diene precursor can be challenging due to instability of the diene due to isomerization or reaction conditions that do not yield the diene in high amounts. In this study, (‐)‐isopulegol was converted to a homoallylic bromide, which was eliminated with 1,8‐diazabicyclo(5.4.0)undec‐7‐ene to cleanly furnish the conjugated diene. The resulting diene was used as a precursor to various dienophiles to give tricyclic frameworks as well as other heterocycles. This new entry into the synthesis of conjugated dienes enabled the generation of a small group of 12 compounds that were tested for antimicrobial properties. Out of the 12 compounds, three showed consistent antimicrobial activities against JE2 and H99 cells (20–107 µg/mL) while the rest of the tested compounds did not possess any antimicrobial property (>128 µg/mL). The bioactive compounds possessed a Michael acceptor motif, suggesting an explanation for their antimicrobial activity.