Absolute Configuration Determination of Two Diastereomeric Neovasifuranones A and B from Fusarium oxysporum R1 by a Combination of Mosher’s Method and Chiroptical Approach

Abstract

Endophytic fungi are one of prolific sources of bioactive natural products with potential application in biomedicine and agriculture. In our continuous search for antimicrobial secondary metabolites from Fusarium oxysporum R1 associated with traditional Chinese medicinal plant Rumex madaio Makino using one strain many compounds (OSMAC) strategy, two diastereomeric polyketides neovasifuranones A (3) and B (4) were obtained from its solid rice medium together with N-(2-phenylethyl)acetamide (1), 1-(3-hydroxy-2-methoxyphenyl)-ethanone (2) and 1,2-seco-trypacidin (5). Their planar structures were unambiguously determined using 1D NMR and MS spectroscopy techniques as well as comparison with the literature data. By a combination of the modified Mosher’s reactions and chiroptical methods using time-dependent density functional theory-electronic circular dichroism (TDDFT-ECD) and optical rotatory dispersion (ORD), the absolute configurations of compounds 3 and 4 are firstly confirmed and, respectively, characterized as (4S,7S,8R), (4S,7S,8S). Bioassay results indicate that these metabolites 1–5 exhibit weak inhibitory effect on Helicobacter pylori 159 with MIC values of ≥16 µg/mL. An in-depth discussion for enhancement of fungal metabolite diversity is also proposed in this work.