New Eunicellin-Type Diterpenes from the Panamanian Octocoral Briareum asbestinum

Abstract

Gorgonian octocorals are considered a prolific source of secondary metabolites with a wide range of biological activities, including anti-inflammatory activity. In particular, the genus Briareum is known for producing a wealth of diterpenes with complex chemical structures. The chemical study of the methanolic extract of Briareum asbestinum collected in Bocas del Toro, on the Caribbean side of Panama, led to the isolation of three new eunicellin-type diterpenes: briarellin T (1), asbestinin 27 (2), asbestinin 28 (3) and the previously described asbestinin 17 (4). The structures of the new compounds were determined by extensive NMR analyses and HRMS. Anti-inflammatory activity assays showed a significant reduction of the pro-inflammatory cytokines TNF-α, IL-6, IL-1β and IL-8 as well as a downregulation of COX-2 expression in LPS-stimulated THP-1 macrophages. These findings support the potential use of these marine compounds as therapeutic agents in the treatment of inflammatory diseases.

Marine natural products

“…A collection of Briareum asbestinum from Isla San Cristobal on the Caribbean coast of Panama yielded three weakly anti-inflammatory eunicellin diterpenoids; briarellin T 1316 , asbestinin 27 1317 and asbestinin 28 1318 . 577 A 2010 publication called into doubt the assigned C-3–C-14 bridged lactone structure of briarellin J, 578 prompting a recent closer examination of the structures of related diterpenoids using DF/DU8+ methodology. 579 What resulted was an exposition of the use of calculated NMR parameters mixed with elements of trial-and-error leading to revision of the structures of briarellins A, B, D, H, J–M, Q and R 1319 and 1320–1328 to those shown.…”

Applications of Norrish type I and II reactions in the total synthesis of natural products: a review

“…Eunicellin, the first member of this family, was isolated from the coral Eunicella strictu, and the related structures including (-)-7-deacetoxyalcyonin acetate was isolated from a Cladiella species of soft coral [107,108]. These diterpenes have received considerable attention from the organic synthetic community due to their structural complexity such as they are distinguished by a unique tricyclic ring system possessing hydroisobenzofuran and oxonane subunit as well as exciting biological activity including anti-inflammatory activity [109,110]. The total synthesis of deacetoxyalcyonin acetate (79) commenced with commercially available α-phellandrene (75) when it was treated with methoxyacetyl chloride in NEt 3 to afford Norrish type I precursor cyclobutanone (76).…”

Polyoxygenated Klysimplexane- and Eunicellin-Based Diterpenoids from the Gorgonian Briareum violaceum

“…Gorgonian corals belonging to genus Briareum (Cnidaria, Octocorallia, Briareidae) inhabiting the western Pacific Ocean and Caribbean waters have been found to be a rich source of diterpenoids [ 1 , 2 ] possessing fused bicarbocyclic structures of briarane [ 3 , 4 , 5 , 6 , 7 ], eunicellin [ 8 , 9 , 10 , 11 ], and asbestinane [ 12 , 13 , 14 ] types, in addition to cembranoids [ 15 , 16 ]. Many of these metabolites exhibit a wide range of bioactivities, including anti-inflammatory [ 3 , 11 , 17 , 18 , 19 , 20 ], cytotoxic [ 14 , 21 , 22 , 23 ], antiviral [ 14 , 21 , 24 ], antimalarial [ 8 ], antimicrobial [ 14 ], and analgesic [ 20 ] activities. Our previous study on the chemical constituents of Briareum violaceum afforded the isolation of briarellins (2,9:3,16-diepoxyeunicellins), which were shown to possess interesting structures generated from intramolecular cyclization of corresponding cembranoids [ 10 ].…”