New indole diketopiperazine alkaloids from a soil-derived fungus Aspergillus ochraceopetaliformis

Prenylated indole derivatives are hybrid natural products containing both aromatic and isoprenoid moieties and are widely spread in terrestrial and marine organisms, these compounds are mainly found in the genera of Claviceps, Penicillium and Aspergillus of Ascomycota [1] [2]. Tryptophan from the primary metabolism is a key precursor for the biosynthesis of the prenylated indole alkaloids and acts as the biogenetic origin of indole rings.[3] Besides L-tryptophan, most of these metabolites contain a second amino acid and form cyclic dipeptides with a diketopiperazine structure or a derivative thereof. However, their final chemical structure may be quite complex. Inspection of the natural indole diketopiperazine IDKP alkaloid chemical structures shows the pervasive presence of a prenyl group on the indole ring. The prenyl group consists of an allylic subunit with at least five carbons [4].

Several prenyl groups can be found at the periphery of these molecules and it is proposed to increase lipophilicity to favour interactions with biological membranes and bioactivity.[5] Prenylated IDKP alkaloids thus possess specific properties that make them good candidates for lead discovery and drug development. During our continuous efforts towards the discovery of new and bioactive secondary metabolites from terrestrial Aspergillus ochraceopetaliformis [6] which was collected at Giza province, Egypt, four new diketopiperazines named as 8-hydroxyechinulin (1), 27,28-epoxyechinulin (2), (12R)dehydroechinulin (3) and neoechinulin F (4), along with ten known compounds (5-14) were isolated. The compounds identified in this work were isolated using multiple chromatographic techniques, and the structures were established based on a detailed analysis of 1D and 2D NMR data combined with HR-ESIMS. The study of the stereochemistry of the isolated compounds was based on 1D and 2D NOESY experiments, Marfey’s analysis, specific optical rotation measurements and thorough comparison with literature data. All isolated compounds were evaluated for their antimicrobial activities against six Gram-positive and Gram-negative bacteria as well as against three human pathogenic fungi.

Publication History

Article published online:
13 December 2021

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