Structurally Diverse Diterpenoids from the Sanya Bay Nudibranch Hexabranchus sanguineus and Its Sponge‐Prey Chelonaplysilla sp.

Abstract

Investigation of the South China Sea nudibranch Hexabranchus sanguineus from Sanya Bay afforded, in addition to three known compounds, nine new diterpenoids of the 5,19‐cycloclerodane‐ (sanyanolides A–D), clerodane‐ (sanyanolide E) and subersin‐ (sanyanolides F–I) type. Remarkably, six diterpenoids aforementioned from H. sanguineus were also isolated from the sponge Chelonaplysilla sp. from the same water region, suggesting a trophic relationship between H. sanguineus and Chelonaplysilla sp. The structure and absolute configuration of new compounds were established by a combination of spectroscopic data, X‐ray diffraction analysis and/or time‐dependent density functional theory/electronic circular dichroism calculations. A plausible biogenetic relationship between these diterpenoids, along with the chemo‐ecological implications of their co‐occurrence in the two organisms investigated, was proposed and discussed. In in vitro bioassays, echinoclerodane A exhibited a potent inhibitory effect (IC50=2.81 μM) on LPS‐induced inflammatory response in RAW 264.7 macrophage cells. In addition, echinoclerodane A and oculatolide showed considerable antibacterial activities with MIC values ranging from 1.0 to 8.0 μg/mL.

Systematic Review of Chemical and Biological Activity Studies of Extracts and Isolated Compounds From Nudibranchs

“…A trophic relationship between the nudibranch H. sanguineus and Chelonaplysilla sp. was suggested by Shen et al [84] and a plausible biogenetic relationship between the diterpenoids isolated was proposed, along with the chemo-ecological implications of their co-occurrence in the two organisms investigated. In in vitro bioassays, echinoclerodane A exhibited a potent inhibitory effect (IC50=2.81 µM) on LPS-induced inflammatory response in RAW 264.7 macrophage cells and echinoclerodane A and oculatolide showed considerable antibacterial activities with MIC values ranging from 1.0 to 8.0 µg/mL.…”

Chemistry, Chemo‐Ecology, and Biological Activities of Uncommon and Structurally Diverse Sesquiterpenoids from the Sanya Bay Nudibranch Hexabranchus sanguineus

“…[14] The only difference between these two compounds was the presence of the double bond C5-C6 in 21. The trisubstituted olefin at Δ 5,6 was supported by the HMBC correlation from H-5 (δ H 5.16 s) to C-12 (δ C 46.8 s). The NOESY cross-peaks (Figure S3) of H-11 (δ H 3.02)/CH 3 -13 (δ H 1.19) and CH 3 -14 (δ H 0.85)/H-2 (δ H 2.02) assigned the relative configuration of spirocarbon (C-3) and C-11 in 21 as 3R*, 11R*.…”

“…In fact, H. sanguineus was previously reported to be prey on the sponges Acanthella cavernosa, Chelonaplysilla sp., and Hulichondria sp., with many common terpene skeletons having been found. For example, cadinane-, spiro [4,5]decane-, eudesmane-and aromadendranetype sesquiterpenoids were found in both H. sanguineus and its sponge prey A. cavernosa; [5] six uncommon 5,19-cycliclerodane-, cycloclerodane-and subersin-type diterpenoids were common secondary metabolites of the tile animal and another sponge prey Chelonaplysilla sp., [6] whereas cytotoxic and antifungal macrolides were strongly suspected to derive from the sponge of the genus Hulichondria. [3] These intriguing pieces of evidence indicated the diverse recipe of the title animal and its ability to take the diverse, and often cytotoxic secondary metabolites for its own biological function, usually for self-defense.…”

“…The nudibranch Hexabranchus sanguineus (class Gastropoda, subclass Heterobranchia, order Nudibranchia, family Hexabranchidae) is a large, brilliantly redcolored shell-less mollusk, distributed throughout the Indo-Pacific region. [3] Literature survey revealed that in addition to cytotoxic and antifungal macrolides, [4] H. sanguineus also contains characteristic sesquiterpenoids [5] and antimicrobial diterpenoids, [6] with many of them being nitrogenous.…”