Stereochemical determination and bioactivity assessment of ( S)-(+)-curcuphenol dimers isolated from the marine sponge Didiscus aceratus and synthesized through laccase biocatalysis

Abstract

Electrospray ionization mass spectrometry-guided isolation of extracts from Didiscus aceratus led to the discovery of several new derivatives of the bioactive bisabolene-type sponge metabolite ( S)-(+)-curcuphenol ( 1). The compounds obtained by this method included a mixture of known ( 2) and new ( 3) dihydroxylated analogs as well as a novel family of dimeric derivatives, dicurcuphenols A–E ( 4– 8), and dicurcuphenol ether F ( 9). Dimers 4– 9 were also subsequently obtained through a hemisynthetic method in which 1 was incubated with the enzyme laccase. Atropisomeric dimers 5 and 6 were subjected to vibrational circular dichroism analysis thereby establishing their absolute biaryl axial chirality as P and M, respectively. In contrast to 1, metabolites 2– 9 exhibited weak or no cytotoxic or lipoxygenase inhibitory effects.