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

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 ? 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 ?-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??M and antifouling activity against the larvae of the barnacle Balanus albicostatus with EC₅₀ value of 11.9 ?g/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??M, respectively. A semisynthetic trial was performed to validate the proposed biosynthetic hypotheses.

SUBMITTER: Li P 

PROVIDER: S-EPMC5550455 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature