Total Synthesis and Antimicrobial Evaluation of 23-Demethyleushearilide and Extensive Antimicrobial Evaluation of All Synthetic Stereoisomers of (16Z,20E)-Eushearilide and (16E,20E)-Eushearilide

Abstract

A novel stereoisomer of eushearilide, 23-demethyleushearilide, was synthesized, and the structure–activity relationships of this compound along with known eushearilide stereoisomers were investigated in order to design novel lead compounds for the treatment of fungal infections. It was discovered that all of these congeners, together with the natural product, exhibited a wide range of antimicrobial activity against not only fungi but also against bacteria, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE).

Enhancing the Discovery of Bioactive Secondary Metabolites From Fungal Endophytes Using Chemical Elicitation and Variation of Fermentation Media

“…Compound 6 ( Figure 6 ) was isolated as pale-yellow sticky oil with [α] D + 1.8 (c 1.2, MeOH) and assigned the molecular formula C 31 H 54 NO 6 P, following analysis of HRESIMS and NMR data. The 1 H NMR spectrum of 6 ( Table 4 ; Supplementary Figure S35 ) was similar to that reported for eushearilide, suggesting their structural resemblance ( Hosoe et al, 2006 ; Tonoi et al, 2019 ). Comparison of 13 C NMR ( Supplementary Figure S36 ) and MS data of 6 to those of eushearilide suggested that 6 was a 26-membered macrolide containing four non-conjugated diene and a choline phosphate ester group.…”

“…In summary, none of the six isolated compounds exhibited better antimicrobial activities than the commercial compounds used as standards in the study. Since the discovery of eushearilide some years back from the E. shearii , only total synthesis of the compound and its various stereoisomers and/or related compounds have been reported ( Tonoi et al, 2016 , 2019 ). This, therefore, is the second time that this class of compounds is being reported from nature.…”

The phosphate ester group in secondary metabolites

“…Later, the same group reported the synthesis of additional eushearilide analogues, and their antifungal and antibiotic activities were evaluated. 86 3.1.7. JBIRs.…”

Discovery and characterization of bioactive compounds from endophytic fungi

“…was isolated as a pale-yellow sticky oil with [α]D + 1.8 (c 1.2, MeOH) and assigned the molecular formula C31H54NO6P, following analysis of HRESIMS and NMR data. The 1 H NMR spectrum of 6 was similar to that reported for eushearilide, suggesting their structural resemblance (Hosoe et al, 2006;Tonoi et al, 2019). Comparison of 13 Tropicicolide presented the strongest antifungal activity against A. fumigatus of all the tested compounds with an IC50 of 1.8 µg/mL but with a lesser activity of an IC50 value of 7.1 µg/mL against the yeast pathogen C. albicans.…”