Diterpene Glycosides and Polyketides from Xylotumulus gibbisporus

Abstract

Four new tetracyclic diterpene glycosides, namely, sordarins C-F (1-4), and three new γ-lactone polyketides, namely, xylogiblactones A-C (5-7), along with sordarin were isolated from the ethyl acetate extracts of the fermented broths of Xylotumulus gibbisporus YMJ863. The structures of 1-7 were elucidated on the basis of spectroscopic data analyses. The configurations of 1-4 were deduced by NOESY, molecular modeling, and comparison with the literature. The relative configurations of 5-7 were deduced by X-ray crystallographic analysis of 5. Compounds 1-5 and sordarin were evaluated in an antifungal assay using Candida albicans ATCC 18804, C. albicans ATCC MYA-2876, and Saccharomyces cerevisiae ATCC 2345, and only sordarin exhibited significant antifungal activities against these fungal strains, with MIC values of 64.0, 32.0, and 32.0 μg/mL, respectively. The effect of compounds 1-7 and sordarin on the inhibition of NO production in lipopolysaccharide-activated murine macrophages was also evaluated. Compounds 2 and sordarin inhibited NO production with IC50 values of 327.2±46.6 and 157.1±24.1 μM, respectively.

Trichosordarin A, a norditerpene glycoside from the marine-derived fungus Trichoderma harzianum R5

“…The connectivity at C-9 was established by the HMBC correlations from H-17a to C-8, C-9, and C-10, from H-17b to C-1, C-8, and C-9, and from H-2 and H-11 to C-9. The remaining 13 C NMR signals, except for that for a carboxyl group, corresponded to a 6-deoxy-4-O-methylaltrose moiety by comparison with literature data (Chang et al 2014), which was also corroborated by the HMBC correlations from H-5 0 to C-1 0 and from CH 3 O-4 0 to C-4 0 and COSY correlations of H-1 0 /H-2 0 /H-3 0 /H-4 0 /H-5 0 /H 3 -6 0 . A glycosidic linkage between C-17 and C-1 0 was established by the HMBC correlation from H 2 -17 to C-1 0 , and a carboxyl group was proposed to be attached to C-1 to satisfy the elemental composition.…”

“…In view of the unusual activity and mechanism of sordarin, several analogues have been naturally isolated or chemically synthesized later, such as sordarins C-F, zofimarin, and FR290581, and their antifungal activities have also been evaluated, especially against Candida spp. (Liang 2008;Hanadate et al 2009;Chang et al 2014). Although a member (sordarin E), obtained from the fungus Xylotumulus gibbisporus, of them possesses no antifungal activity, its structure differs from the others due to the presence of an unprecedented spiro-methylcyclopropyl moiety (Chang et al 2014).…”

“…(Liang 2008;Hanadate et al 2009;Chang et al 2014). Although a member (sordarin E), obtained from the fungus Xylotumulus gibbisporus, of them possesses no antifungal activity, its structure differs from the others due to the presence of an unprecedented spiro-methylcyclopropyl moiety (Chang et al 2014). To date, no other cyclopropylbearing derivatives of sordarin have been isolated or synthesized.…”

A recent survey of naturally occurring organohalogen compounds

“…from the Kerama Islands, Okinawa, has yielded the extraordinarily complex agelamadins A (25), B (26), C (27), D (28) and E (29) (Scheme 7). [8,9] Whereas 25 and 26 possess the agelastatinoroidin hybrid structure, 27-29 contain a combination of oroidin and 3-hydroxykynurenine.…”

“…[27] In addition to several nonhalogenated tetracyclic diterpene glycosides, this fungus yielded the new g-lactone polyketide xylogiblactone A (99) (Scheme 25).…”