Synthesis of Berkeleylactone A by Ring‐Closing Alkyne Metathesis

Abstract

AbstractA new route to the macrolactone antibiotic berkeleylactone A was developed. As a key step, a ring‐closing alkyne metathesis (RCAM) of an ester substrate featuring 1‐propynyl termini was used. The carboxylic part of the substrate was easily assembled using alkyne chemistry, like carboxylation of a diyne followed by isomerization of the ynoate section to a dienoate and dihydroxylation of the 4,5‐double bond. The synthesis of the alcohol part of the ester started with opening of (R)‐propylene oxide with an acetylide and was followed by two triple bond migrations. After successful RCAM which formed the C8−C9 bond, the triple bond was selectively hydrogenated to the corresponding alkene before the 4,5‐diol was oxidized to the 5‐hydroxy‐4‐oxo derivative. At this stage, the thioether was formed and the 8,9‐double bond reduced. We also prepared the 8,9‐didehydro analog of berkeleylactone A. However, it turned out that its antimicrobial activity was slightly reduced.