The pseudopterosins: anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae.

Abstract

The Caribbean sea whip Pseudopterogorgia elisabethae (Octocorallia, Cnidaria) has been found to contain the pseudopterosins, a newly described class of natural products, which have been characterized as diterpene-pentoseglycosides. The pseudopterosins possess anti-inflammatory and analgesic properties that exceed, in our assays, the potencies of existing drugs such as indomethacin. As anti-inflammatory agents, the pseudopterosins appear to modify the arachidonic acid cascade by an as yet undefined mechanism of pharmacological action.As part of a continuing program to explore the chemical adaptations of marine organisms and to assess the biomedical applications of marine metabolites, we have focused considerable attention on the chemically rich sea fans and whips (gorgonian soft-corals) found in the Caribbean Sea (1-5). During an expedition on board the research vessel Calanus,5 our attention was drawn to several sea whips of the genus Pseudopterogorgia found generally at depths in excess of 20 m. The highly branched Pseudopterogorgia elisabethae was ofparticular interest since ship-board chemical and biological assays revealed this animal to contain large quantities of unknown, polar-lipid metabolites that were apparently coupled with strong inhibitory activities in field-oriented antimicrobial and cytotoxicity assays.bc Subsequent mass collection, extraction, and fractionation of the extract of P. elisabethae has now resulted in the isolation of pseudopterosins A-D (14), highly bioactive diterpenoid glycosides, which are responsible for these potent activities.Chemistry of the Pseudopterosins Purification of pseudopterosins A-D was achieved by sequential silica gel chromatography including HPLC. Pseudopterosin A (1), the most polar metabolite, was assigned the molecular formula C25H3606 by high-resolution mass spectrometry and by analysis of 13C NMR data ( Table 1). The eight degrees of unsaturation in this molecular formula were assigned to a fully substituted benzene ring, one trisubstituted olefinic bond (gem-dimethyl), a cyclic hemiacetal, and two carbocyclic rings on the basis of NMR and other spectral data.d Characteristic 13C NMR features, infrared spectral data for hydroxyl (ca. 3400 cm-1), and a base-induced bathochromic shift of the UV absorption of 1 showed this metabolite to be phenolic.Acetylation of pseudopterosin A (Ac20/py/RT) yielded a tetraacetate, 5, which proved that 1 contained at least four hydroxyl groups. In a consistent fashion, acetylation of each of the pseudopterosins, B(2), C(3), and D(4), produced the same tetraacetate, 5, in nearly quantitative yield. Since the molecular formulas of these latter compounds were that of pseudopterosin A (C25H3606) + C2H20, the less polar pseudopterosins were concluded to be monoacetate positional isomers of 1.Inspection of the high resolution mass spectrometry data for 1 showed that the base peak represented M+ -C5H804fragmentation. This behavior, coupled with the presence of three nonphenolic hydroxyl groups and an acetal constellation, st...

Ligand Tuning in Asymmetric Hydrovinylation of 1,3-Dienes: A Stereoselective Route to Either Steroid-C20 (S) or -C20 (R) Derivatives

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Comparison of two total RNA extraction protocols using the marine gorgonian coral Pseudopterogorgia elisabethae and its symbiont Symbiodinium sp

“…The Caribbean gorgonian Pseudopterogorgia elisabethae is the source of potent antiinflammatory agents, the pseudopterosins (Look et al 1986a;Look et al 1986b). Evidence suggests that the biosynthetic machinery for pseudopterosin biosynthesis is located in P. elisabethae's symbiont, the dinoflagellate Symbiodinium sp.…”

Molecular biology in marine science: Scientific questions, technological approaches, and practical implications

“…Recent studies o f marine invertebrates have shown that they contain substances, many of which are defensive compounds, with significant potential for treatment of many human diseases. Marine invertebrate animals have already yielded substances that appear promising for the treatment of cancer (de Silva and Scheuer, 1980;Rinehart et at., 1981;Look et al, 1986).…”