Broomeanamides: Cyclic Octapeptides from an Isolate of the Fungicolous Ascomycete Sphaerostilbella broomeana from India.

Dulamini I Ekanayake,Kadri Põldmaa,Dale C Swenson,Bruno Perlatti,James B Gloer,Gerald F Bills

doi:10.1021/acs.jnatprod.1c00414

Dulamini I Ekanayake, Kadri Põldmaa + Show 4 more

Open Access

https://doi.org/10.1021/acs.jnatprod.1c00414

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Abstract

The genus Sphaerostilbella comprises fungi that colonize basidiomata of wood-inhabiting fungi, including important forest pathogens. Studies of fermentation cultures of an isolate (TFC201724) collected on the foothills of Himalayas, and closely related to S. broomeana isolates from Europe, led to the identification of a new cyclic octapeptide along with two closely related analogues (1–3) and four dioxopiperazines (4–7). The structure of the lead compound, broomeanamide A (1), was assigned mainly by analysis of 2D NMR and HRESIMS data. The structure consisted of one unit each of N-MeVal, Ala, N-MePhe, Pro, Val, and Ile and two N-MeLeu units. The amino acid sequence was determined on the basis of 2D NMR and HRESIMSMS data. NMR and HRMS data revealed that the other two new peptides have the same amino acid composition except that the Ile unit was replaced with Val in one instance (2) and the N-MeVal unit was replaced with Val in the other (3). The absolute configuration of 1 was assigned by analysis of the acid hydrolysate by application of Marfey’s method using both C18 and C3 bonded-phase columns. Broomeanamide A (1) showed antifungal activity against Cryptococcus neoformans and Candida albicans, with MIC values of 8.0 and 64 μg/mL, respectively.

Highlights

The genus Sphaerostilbella comprises fungi that colonize basidiomata of wood-inhabiting fungi, including important forest pathogens
The high rate of morbidity and mortality associated with microbial infections and the development of multidrug resistance by infectious agents continue to intensify the need for new antimicrobial agents
The genus Sphaerostilbella is exceptional in the family because of the tendency to specialize on wood-inhabiting members of the Russulales, an order well known for its agaric members from the large genera of Russula and Lactarius

Summary

■ RESULTS AND DISCUSSION

A solid-substrate rice fermentation of S. broomeana TFC201724 was extracted with EtOAc, and the resulting extract was partitioned between acetonitrile and hexanes. Broomeanamide B [2]: white solid; [α]20D −18 (c 0.03, MeOH); 1H and 13C NMR and HMBC data, see Table S1; positive ion HRESIMS m/z 895.6032 [M + H]+ (calcd for C48H78N8O8 + H, 895.6021). A colorless plate-like crystal (0.030 × 0.170 × 0.205 mm) was obtained by evaporation from MeOH, separated from the sample, and mounted on a glass fiber, and data were collected using Incoatec microsource 3.0 Cu Kα radiation, λ = 0.710 73 Å at 150(2) K.

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■ ACKNOWLEDGMENTS

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