Unusual Inner-Salt Guaiazulene Alkaloids and bis-Sesquiterpene from the South China Sea Gorgonian Muriceides collaris

Abstract

Abstract Three new guaiazulene alkaloids muriceidines A–C (1–3) and one new bis-sesquiterpene muriceidone A (4), were isolated from the South China Sea gorgonian Muriceides collaris. Muriceidines are the first examples structurally architected by guaiazulene coupling with an inner-salt Δ 1-pipecolic acid via a unique sp2 methine-bridged linkage, and the bis-sesquiterpene was comprised by a guaiazulene and a indene units linked through a unprecedented carbon-carbon σ-bond between the high steric bridgehead carbon C-10 of guaiazulene moiety and C-2′ of indene moiety. The chiral compounds 2–4 were obtained initially as racemates and further separated by chiral HPLC methods. The inner-salt structures of 1–3 and absolute configurations of 2–4 were fully elucidated by calculated 13C NMR, ECD and OR with quantum chemical calculation methods. Compound 1 showed cytotoxicity against K562 cell lines with IC50 value of 8.4 μM and antifouling activity against the larvae of the barnacle Balanus albicostatus with EC50 value of 11.9 μg/mL and potent therapeutic index (LC50/EC50 = 3.66). Also the racemic (±)-3 showed cytotoxicities against both HL-60 and K562 cell lines with IC50 values of 2.2 and 3.7 μM, respectively. A semisynthetic trial was performed to validate the proposed biosynthetic hypotheses.