Antiviral Cyclopropane Acids from Deep-Sea-Derived Fungus Aspergillus sydowii

Abstract

Four novel monocyclic cyclopropane acids, namely, sydocyclopropanes A-D (1-4), along with one known congener hamavellone B (5), were isolated from the Aspergillus sydowii MCCC 3A00324 fungus, which was isolated from the deep-sea sediment. The gross structures of novel compounds were established by detailed analyses of the spectroscopic data (HRESIMS and NMR spectra), and their absolute configurations were resolved on the basis of the quantum chemical calculations of ECD and NMR data, in association with DP4+ probability analyses. Sydocyclopropanes A-D, featuring the 1,1,2,3-tetrasubstituted cyclopropane nucleus with different lengthy alkyl side chains, were discovered in nature for the first time. All compounds exhibited antiviral activities against A/WSN/33 (H1N1), with IC₅₀ values ranging from 26.7 to 77.2 μM, of which compound 1 exhibited a moderate inhibitory effect (IC₅₀ = 26.7 μM).

Keywords: Aspergillus sydowii; H1N1; antiviral activities; cyclopropane; deep-sea-derived fungus.

Figure 1

Chemical structures of the isolated metabolites 1–5.

Figure 2

COSY () and key HMBC () correlations of 1–3.

Figure 3

Key NOESY correlations of compounds 1–4.

Figure 4

Experimental ECD spectrum of 1 in MeOH and the calculated ECD data of (1S,2S,3S)−1 and (1R,2R,3R)−1 at the B3LYP/6−311G(2d,p) level.

Figure 5

Experimental and calculated ECD spectra of 2.

Figure 6

Experimental and calculated ECD data of 3.

Figure 7

Experimental and calculated ECD spectra of 4.