Antifungal bromopyrrole alkaloids from the South China Sea sponge Agelas sp.

Abstract

Six new bromopyrrole alkaloids, longamides D–F (1–3), 3-oxethyl-4-[1-(4,5-dibromopyrrole-2-yl)-formamido]-butanoic acid methyl ester (4), 2-oxethyl-3-[1-(4,5-dibromopyrrole-2-yl)-formamido]-methyl propionate (5), and 9-oxethyl-mukanadin F (6), along with two known metabolites, hanishin (7) and longamide B methyl ester (8), were isolated from the South China Sea sponge Agelas sp. The racemic mixtures 1–5, 7 and 8 were resolved into seven pairs of enantiomers 1a/1b–5a/5b, 7a/7b, and 8a/8b through HPLC using a Chiralcel OJ-RH column. The structures were elucidated on the basis of spectroscopic data. The absolute configurations of each enantiomer of (±)-1 and (±)-2 were established through the quantum mechanical calculations of the corresponding electronic circular dichroism (ECD) spectra and using the CD exciton chirality method, respectively, whereas the absolute configurations of 3a and 3b were confirmed by comparing the experimental CD spectra with that of (−)-S-longamide B methyl ester. Individual enantiomers (+)-(9S, 10R)-1a, (−)-S-2b, (+)-R-3a, (+)-R-7a, and (+)-R-8a exhibited effective antifungal activity against Candida albicans in a Caenorhabditis elegans candidiasis model.