Structures of New Bromopyrrole Alkaloids from an Okinawan Marine Sponge Agelas sp.

<p>Bromopyrrole alkaloids are known to be one of the most common metabolites contained in marine sponges. These alkaloids have attracted widespread interest due to their fascinating chemical structures with high N to C ratio (~1:2) and intriguing biological activities. In our search for new metabolites from marine organisms, we have reported several bromopyrrole alkaloids from the extract of an Okinawan marine sponge Agelas sp. (SS-162). Further investigation of the extract has resulted in the isolation of five new bromopyrrole alkaloids, agelamadins A-E (1-5). The structures of 1-5 were elucidated on the basis of detailed spectroscopic analysis and TDDFT ECD calculation.</p><p>Agelamadins A (1) and B (2) are structurally unique dimeric bromopyrrole alkaloids having an agelastatin-like 5/5/6/5 tetracyclic moiety and an oroidin-like liner moiety in common. Agelamadins A (1) and B (2) were assigned as racemate by chiral HPLC analysis. Agelamadins C-E (3-5) are bromopyrrole alkaloids with a bicyclic skeleton including a fused morpholine and benzene moieties. The absolute configuration of the a-carbon of 3 was assigned as S by application of PGME method. To the best of our knowledge, agelamadins C-E (3-5) are the first example for heterodimers comprising a bromopyrrole alkaloid and a tryptophan derivative. </p><p>Agelamadins A (1) and B (2) exhibited antimicrobial activity against Bacillus subtilis (MIC, 16 mg/mL, each), Micrococcus luteus (MIC, 4.0 and 8.0 mg/mL, respectively), and Cryptococcus neoformans (IC₅₀, 8.0 and 4.0 mg/mL, respectively). </p>