Synthesis of Berkeleylactone A by Ring-Closing Alkyne Metathesis |
| |
Authors: | MSc Frank Schmidt Dr Aparna Viswanathan Ammanath Prof Dr Friedrich Götz Prof Dr Martin E Maier |
| |
Institution: | 1. Eberhard Karls Universität Tübingen, Institut für Organische Chemie, Auf der Morgenstelle 18, 72076 Tübingen, Germany;2. Eberhard Karls Universität Tübingen, Mikrobielle Genetik, Interfakultäres Institut für Mikrobiologie und Infektionsmedizin Tübingen (IMIT), Auf der Morgenstelle 28, 72076 Tübingen, Germany |
| |
Abstract: | A 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. |
| |
Keywords: | alkyne isomerization antibiotics asymmetric dihydroxylation berkeleylactone A ring-closing alkyne metathesis |
|
|