Dactylfungins and Tetralones: Bioactive Metabolites from a Nematode-Associated Laburnicola nematophila

Abstract

A chemical investigation of Laburnicola nematophila, isolated from cysts of the plant parasitic nematode Heterodera filipjevi, affored three dactylfungin derivatives (1-3) and three tetralone congeners (4-6). Dactylfungin C (1), laburnicolin (4), and laburnicolenone (5) are previously undescribed natural products. Chemical structures of the isolated compounds were determined based on 1D and 2D NMR spectroscopic analyses together with HR-ESI-MS spectrometry and comparison with data reported in the literature. The relative configurations of compounds 1, 2, and 4-6 were determined based on their ROESY data and analysis of their coupling constants (J values). The absolute configurations of 4-6 were determined through the comparison of their measured and calculated TDDFT-ECD spectra. Compounds 1-3 were active against azole-resistant Aspergillus fumigatus.

Figure 1

Key ¹H–¹H COSY, HMBC, and ROESY correlations of 1 and 2.

Figure 2

A plausible biosynthetic pathway of 1.

Figure 3

Key ¹H–¹H COSY, HMBC, and ROESY correlations of 4 and 5.

Figure 4

A plausible biosynthetic pathway of 4 and 6.

Figure 5

Experimental ECD spectrum of 5 in MeOH compared with the BH&HLYP/TZVP PCM/MeOH ECD spectrum of (R)-5 computed for the low-energy ωB97X/TZVP PCM/MeOH conformers. The bars represent the rotational strength values of the lowest-energy conformer.

Figure 6

Overlapped geometries for two groups of the low-energy ωB97X/TZVP PCM/MeOH conformers of (R)-5: group A with M helicity and an equatorial hydroxy group represented by conformers A–H, and group B with P helicity and an axial hydroxy group represented by conformers I–P.

Figure 7

Experimental ECD spectrum of 6 measured in MeOH compared with the CAM-B3LYP/TZVP PCM/MeOH ECD spectrum of (R)-6 computed for the low-energy ωB97X/TZVP PCM/MeOH conformers. The bars represent the rotational strength values of the lowest-energy conformer.

Figure 8

Two groups of the low-energy ωB97X/TZVP PCM/MeOH conformers of (R)-6: group A with M helicity and an equatorial hydroxy group represented by conformers A–H, and group B with P helicity and an axial hydroxy group represented by conformers I–P.