Isolation and Identification of Cissetin-A Setin-like Antibiotic with a Novel cis-Octalin Ring Fusion

Abstract

In our search for fungal metabolites with antibiotic activity against methicillin-resistant Staphylococcus aureus (MRSA), we have isolated three different setin antibiotics from several different fungi-the previously reported equisetin (2)1) and trichosetin (3),2) and a novel setin-like compound (1) from OSI 50185. Like the known setin antibiotics, cissetin (1) is active against several Grampositive organisms,2-5) but it is most notable for the atypical cis ring fusion in the octalin portion of the molecule.Cissetin (1) was isolated from OSI 50185 as a white foamy powder for which positive ion detection HR-FAB-MS suggested a molecular formula of C23H33NO4 [m/z, found 388.24893 (M+H)+, calcd 388.24892]. In contrast to reports of the NMR data for the setin class as extremely broad and ill-defined,1-5) 1 gave crisp, clean 1H and 13C NMR spectra in CDCl3 at ambient temperature (Table 1)

Natural products containing ‘decalin’ motif in microorganisms

“…83 Compound 108, with a cis-decalin unit, has the same compound name as the trans-decalin derivative 107. Solanapyrones J-M (111)(112)(113)(114), new solanapyrone analogues with modest antifungal and antibacterial activities, were obtained from an unidentied fungicolous fungus. 84 Nigrosporapyrones A-C (115)(116)(117) were isolated from the marine-derived fungus Nigrospora.…”

“…Cissetin (131) with a cis-decalin ring fusion exhibited similar antibiotic activities as those of compounds 125 and 130 containing a different trans-decalin system, suggesting the possible biological function of tetramic acid. 112 Ophiosetin (132) was isolated from the mycopathogenic fungus Elaphocordyceps ophioglossoides. 113 Co-culture of the fungus Fusarium pallidoroseum with the bacterium Saccharopolyspora erythraea afforded N-demethylophiosetin (133) and pallidorosetins A and B (134,135), along with compounds 125 and 132.…”

Hymenosetin, a 3-decalinoyltetramic acid antibiotic from cultures of the ash dieback pathogen, Hymenoscyphus pseudoalbidus

“…In addition, many of them showed cytotoxic effects (Schobert & Schlenk, 2008). For some of these compounds, antifungal activity against the yeast, Candida albicans, has also been described (Boros et al, 2003;Segeth et al, 2003).…”

Isolation of Pyrrolocins A–C: cis- and trans-Decalin Tetramic Acid Antibiotics from an Endophytic Fungal-Derived Pathway

“…Tetramic acids are characterized by the presence of a 2,4-pyrrolidinedione moiety in their structures. Tetramic acids that are related to equisetin are particularly important because of their reported antimicrobial activities, ,− HIV-1 integrase inhibition, , and microtubule assembly inhibition . The mechanism of their antimicrobial activities has been purported to be due to inhibition of SecA, inhibition of undecaprenyl pyrophosphate synthase, and inhibition of the histidine kinase WalK .…”