posted on 2021-03-25, 19:57authored bySonja
L. Knowles, Christopher D. Roberts, Mario Augustinović, Laura Flores-Bocanegra, Huzefa A. Raja, Kimberly N. Heath-Borrero, Joanna E. Burdette, Joseph O. Falkinham III, Cedric J. Pearce, Nicholas H. Oberlies
Four new bislactones, dihydroacremonol
(1), clonostachyone
(2), acremodiol B (3), and acremodiol C
(4), along with one known compound, hymeglusin (5), were isolated from cultures of two fungal strains (MSX59876
and MSX59260). Both strains were identified based on phylogenetic
analysis of molecular data as Clonostachys spp.;
yet, they biosynthesized a suite of related, but different, secondary
metabolites. Given the challenges associated with elucidating the
structures and configurations of bislactones, GIAO NMR calculations
were tested as a complement to traditional NMR and HRESIMS experiments.
Fortuitously, the enantiomer of the new natural product (4) was known as a synthetic compound, and the predicted configuration
from GIAO NMR calculations (i.e., for the relative configuration)
and optical rotation calculations (i.e., for the absolute configuration)
matched those of the synthesis product. These results engendered confidence
in using similar procedures, particularly the mixture of GIAO NMR
shift calculations coupled with an orthogonal technique, to predict
the configuration of 1–3; however,
there were important limitations, which are discussed for each of
these. The metabolites displayed antimicrobial activities, with compounds 1 and 4 being the most potent against Staphylococcus aureus with MICs of 1 and 4 μg/mL,
respectively.