Isolation of Ten New Sesquiterpenes and New Abietane-Type Diterpenoid with Immunosuppressive Activity from Marine Fungus Eutypella sp

Abstract

Background: Ten new sesquiterpenes, including eight eremophilane-type sesquiterpenes (1-8) and two compounds (9-10) with a cyclopentane ring, representing an undescribed subtype of sesquiterpene, along with a new abietane-type diterpenoid (11), were isolated and identified from a deep-sea-derived fungus: Eutypella sp. Methods: Their structures were elucidated on the basis of various spectroscopic analyses, mainly including nuclear magnetic resonance (NMR) and high-resolution electrospray ionization mass spectrometry (HRESIMS) data, ¹³C NMR calculations with DP4+ probability analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction experiments. Results: Furthermore, compound 11 exhibited potent immunosuppressive activity with IC₅₀ values of 8.99 ± 1.08 μM in a lipopolysaccharide (LPS) model and 5.39 ± 0.20 μM in a concanavalin A (ConA) model.

Keywords: Eutypella sp.; immunosuppressive activity; secondary metabolites; sesquiterpenes.

Figure 1

Structures of compounds 1–11.

Figure 2

The key ¹H−¹H COSY and HMBCs of compounds 1–11.

Figure 3

The key NOESY correlations of compounds 1–11.

Figure 4

Experimental and calculated ECD spectra of compounds 1–3, 5.

Figure 5

X-ray crystal structures of compounds 4 and 7. Black represents C atoms, blue represents H atoms, red represents O atoms.

Figure 6

Experimental and calculated ECD spectra of compounds 6, 8–10.

Figure 7

ECD spectra of the Mo₂(AcO)₄ complex of compound 10.

Figure 8

¹³ C NMR calculation results of two possible isomers of compound 10.

Figure 9

Experimental and calculated ECD spectra of compound 11.