Antifungal alkaloids from Agelas Citrina that decouple calcium-dependent excitation-contraction

Several species of Agelas marine sponges produce a special class of paired diterpenoid alkaloids: C₂₀ rearranged diterpenes C-linked to either hypotaurocyamine or 9-N-methyladeninium salts. We describe here three new alkaloids and several known compounds from Agelas citrina, collected in the Bahamas, that exhibit potent antifungal activity and unique properties that affect critical components of Ca²⁺-dependent smooth muscle excitation-contraction: decoupling of the dihydropyridine receptor (DHPR) from Ca²⁺ release through the RyR-1 Ca²⁺ channel of the sarcoplasmic reticulum (SR). Structure elucidation of the new compounds was accomplished by interpretation of MS and NMR data, chemical correlation and quantitative analysis of molar rotations through van't Hoff's principle of optical superposition. The biological activity of new and known diterpenoid alkaloids will be described.