Duvnjak Mirko, Talajić Gregor, Baranašić Jurica, Baus Topić Nea, Čipčić Paljetak Hana, Cindro Nikola
Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, 10000 Zagreb, Croatia.
Ruđer Bošković Institute, Bijenička c. 54, 10000 Zagreb, Croatia.
Int J Mol Sci. 2025 Jul 11;26(14):6643. doi: 10.3390/ijms26146643.
Penicyclone A is a polyketide compound with a unique and intriguing structure recently isolated from the fungus 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.
青霉环素A是一种聚酮化合物，结构独特且引人关注，最近在一次“一种菌株，多种化合物”（OSMAC）研究中从真菌sp. F23 - 2中分离得到。该化合物显示出显著的抗菌活性，且未表现出任何细胞毒性作用，这促使我们对报道的对映体进行全合成。合成完成后，我们发现我们的合成化合物缺乏抗菌活性。进一步分析表明，实际上天然产物可能是与报道的对映体相反的对映体。这一观察结果促使我们使用之前开发的合成序列合成对映体，并评估最终化合物以及两个对映体系列中所选中间体的生物活性（通过抗菌和细胞毒性测定）。
