Polyketides from Marine-Derived Aspergillus porosus: Challenges and Opportunities for Determining Absolute Configuration

Abstract

Fungal natural products have inspired and enabled countless modern therapeutics. During a survey of the secondary metabolites of endophytic fungi, we found that Aspergillus porosus produces new polyketides with interesting structural features named porosuphenols A-D (1, 2, 3a, and 3b). The structural elucidation of these metabolites was performed with 1D and 2D NMR techniques, Mosher ester analysis, J-based conformational analysis, and isotope exchange studies. The absolute configuration of these compounds was determined using typical approaches including comparative analysis of experimental NMR and electronic circular dichroism spectra with DFT calculations. However, these efforts did not provide conclusive results for porosuphenol A (1). To resolve this issue, we applied a strategy in which NMR data guide the conformer search. Herein are presented the structure elucidation of porosuphenols A-D as a case study in the challenges and opportunities for determination of absolute configuration. Lastly, bioassay-guided fractionation of cytotoxic fractions resulted in the additional isolation of pimarane diterpenes, sphaeropsidin A (4), and aspergiloid E (5).