Total Synthesis of (+)-Penicyclone A and Evaluation of Biological Activity Including Intermediate Compounds
Mirko Duvnjak, Gregor Talajić, Jurica Baranašić, Nea Baus Topić, Hana Čipčić Paljetak, Nikola Cindro
TL;DR
Scientists synthesized a natural compound called Penicyclone A and found that its mirror-image version might be the active form.
Contribution
The study clarifies the correct enantiomer of Penicyclone A and evaluates the biological activity of both enantiomers and their intermediates.
Findings
The synthetic compound lacked antimicrobial activity, suggesting the natural product may be the opposite enantiomer.
The antipodal enantiomer was synthesized and tested for antibacterial and cytotoxic effects.
Biological activity was evaluated for both enantiomers and selected intermediates.
Abstract
Penicyclone A is a polyketide compound with a unique and intriguing structure recently isolated from the fungus Penicillium sp. F23-2 during an OSMAC (one-strain-many-compounds) campaign. The compound demonstrated significant antimicrobial activity without exhibiting any cytotoxic effects, which prompted us to pursue total synthesis of the reported enantiomer. Upon completion of the synthesis, we observed that our synthetic compound lacked antimicrobial activity. Further analysis suggested that the natural product may have, in fact, been the opposite enantiomer to that reported. This observation led us to synthesize the antipodal enantiomer using our previously developed synthetic sequence and to evaluate the biological activity (via antibacterial and cytotoxicity assays) of both the final compound and the selected intermediates from both enantiomeric series.
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Taxonomy
TopicsMicrobial Natural Products and Biosynthesis · Synthetic Organic Chemistry Methods · Chemical synthesis and alkaloids