Opportunities and Limitations for Assigning Relative Configurations of Antibacterial Bislactones using GIAO NMR Shift Calculations

Abstract

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.

Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives

“…(iii) Isolation and identification of secondary metabolites. After comparison of the UPLC-HRMS data, the defatted organic layers for each condition were combined due to the similarity of their chemical profiles, so as to generate a larger pool of material for isolation studies, which were carried out using well-established natural products chemistry procedures ( 131 , 132 ). The fractions were dissolved in CHCl 3 -MeOH, absorbed onto Celite 545 (Acros Organics), and fractioned by normal-phase flash chromatography using a gradient of hexane-CHCl 3 -MeOH.…”

Genomic and phenotypic trait variation of the opportunistic human pathogen Aspergillus flavus and its non-pathogenic close relatives

“…After comparison of the UPLC-HRMS data, the defatted organic layers for each condition were combined due to the similarity of their chemical profiles, so as to generate a larger pool of material for isolation studies, which were carried out using well established natural products chemistry procedures (53, 54). The fractions were dissolved in CHCl 3 -MeOH, absorbed onto Celite 545 (Acros Organics), and fractioned by normal phase flash chromatography using a gradient of hexane-CHCl 3 -MeOH.…”

Nuclear Magnetic Resonance

“…88 Experimental spectroscopic and GIAO NMR calculations enabled structure revision of previously proposed analogues of penitol A and penicitols E-I. 89 GIAO NMR shift calculations were also used for assigning relative configurations of antibacterial bislactones 90 and structure of garcipaucinones A and B, derived from Garcinia paucinervis. 91 New alkaloids, spirocollequins A and B were isolated from Colletotrichum boninense and their structures were proposed from the experimental multidimensional NMR studies supported by GIAO calculations and advanced statistical treatment.…”