Unusual dimeric tetrahydroxanthone derivatives from Aspergillus lentulus and the determination of their axial chiralities

Abstract

The research on secondary metabolites of Aspergillus lentulus afforded eight unusual heterodimeric tetrahydroxanthone derivatives, lentulins A−H (2−9), along with the known compound neosartorin (1). Compounds 1−6 exhibited potent antimicrobial activities especially against methicillin-resistant Staphylococci. Their absolute configurations, particularly the axial chiralities, were unambiguously demonstrated by a combination of electronic circular dichroism (ECD), Rh2(OCOCF3)4-induced ECD experiments, modified Mosher methods, and chemical conversions. Interestingly, compounds 1–4 were the first samples of atropisomers within the dimeric tetrahydroxanthone class. Further investigation of the relationships between their axial chiralities and ECD Cotton effects led to the proposal of a specific CD Exciton Chirality rule to determine the axial chiralities in dimeric tetrahydroxanthones and their derivatives.

Genetic Characterization of Neosartorin Biosynthesis Provides Insight into Heterodimeric Natural Product Generation

“…Neosartorin ( 1 ), isolated from several different fungal species, is a xanthone dimer and reportedly exhibits substantial antibacterial activity against several Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) . Although xanthones and xanthone dimers are widespread in nature, 1 features a characteristic molecular skeleton that consists of two different monomeric units (Figure A), and such a heterodimeric nature is relatively rare for xanthone dimers.…”

Antiosteoporotic Tetrahydroxanthone Dimers from Aspergillus brunneoviolaceusFB‐2 Residing in Human Gut

“…Dimeric xanthones are structurally interesting secondary metabolites of plants, fungi, and lichens. [ 29‐30 ] They exhibit diverse biological properties, including cytotoxicity, [ 31‐33 ] antibacterial, [ 34‐36 ] antifungal, [ 37 ] innate immune‐promoting, [ 38‐40 ] and proangiogenic [ 18 ] activities. This work describes the simultaneous production and antiosteoporotic action of tetrahydroxanthone homodimers ( 1 — 5 ) and xanthone‐chromanone heterodimer ( 6 ) by a single fungal strain, which is much rarer.…”

Phialomyces macrosporus: Chemical Constituents, Antimicrobial Activity and Complete NMR Assignments for the 7,7′‐Biphyscion

“…In the case of biphyscion, the restricted rotation occurs along with the single bond between the two aromatic rings (in this system, the axis connecting these rings constitute the center of chirality, imposed by the ortho ‐substituted aryl system 7,7′). The optical purity of biaryls occurring in nature can diverge widely, although many of them are produced in an atropisomerically pure form, while others have been isolated as racemates or scalemic (enantiomerically enriched) forms and their biogenesis is generally not well understood . The optical activity of 2 was measured, with a value of [ α ] D 25 =−174 ( c =0.1 in CHCl 3 ), thus demonstrating the prevalence of one atropoisomer, the (−)‐7,7′‐biphyscion.…”