Anti-Cryptococcus Phenalenones and Cyclic Tetrapeptides from Auxarthron pseudauxarthron

Abstract

Auxarthrones A-E (1-5), five new phenalenones, and two new naturally occurring cyclic tetrapeptides, auxarthrides A (7) and B (8), were obtained from three different solvent extracts of cultures of the coprophilous fungus Auxarthron pseudauxarthron. Auxarthrones C (3) and E (5) possess an unusual 7a,8-dihydrocyclopenta[a]phenalene-7,9-dione ring system that has not been previously observed in natural products. Formation of 1-5 was found to be dependent on the solvent used for culture extraction. The structures of these new compounds were elucidated primarily by analysis of NMR and MS data. Auxarthrone A (1) was obtained as a mixture of chromatographically inseparable racemic diastereomers (1a and 1b) that cocrystallized, enabling confirmation of their structures by X-ray crystallography. The absolute configurations of 7 and 8 were assigned by analysis of their acid hydrolysates using Marfey's method. Compound 1 displayed moderate antifungal activity against Cryptococcus neoformans and Candida albicans, but did not affect human cancer cell lines.

Figure 1

(A) LC-UV analysis of the different solvent extracts of cultures of the fungus Auxarthron pseudauxarthron. (B) Bioassay results for the different solvent extracts. E: ethyl acetate extract; M: methyl ethyl ketone extract; A: acetone extract; P: 3-pentanone extract; Am: amphotericin B; C.N.: C. neoformans; C.A.: C. albicans.

Figure 2

Thermal ellipsoid representations of 1a and 1b.

Figure 3

Selected 2D NMR correlations for 7 and 8.

Scheme 1

Proposed Pathways Leading to Formation of Compounds 1–6