Pseudopterosins from Pseudopterogorgia

A C9-C14 cycHzation forms the ring C and leads to the amphilectane skeleton which is foimd for instance in pseudopterosins A-F (10, aglycone) [10] isolated from Pseudopterogorgia elisabethae extracts stemming from a Bahamian collection site (Fig. 5). This class of natural products can be characterized as... 

Compounds in bold have been isolated from Pseudopterogorgia elisabethae and P. kallos Figure 20.64 Biosynthesis of pseudopterosins (Kohl and Kerr, 2003 Ferns and Kerr, 2005 Duque et al., 2006). 

The pseudopterosins and seco-pseudopterosin isolated from Bahamian specimens of Pseudopterogorgia elisabethae display strong anti-inflammatory and analgesic activity. These diterpene glycosides had potencies superior to those of... 

Caribbean coral Pseudopterogorgia elisabethae discovered by Fenical et al. [47], Pseudopterosin E, Fig. (3) is the one with the best pharmacological profile, combining low toxicity and potent antiinflammatory activity. In human neutrophils, pseudopterosin E inhibits degranulation and formation of Ieukotrienes [2], In 1991, phase I clinical trials were initiated with pseudopterosin E as a topical anti-inflammatory agent. Recently, novel anti-inflammatory natural products have been isolated from this Caribbean soft coral [48,49], Japanese researchers reported the isolation of a group of compounds designated helioporins A-E, which are related to the pseudopterosins [1],... 

Mayer, A. M. S., Jacobson, P. B., Fenical, W., Jacobs, R. S., and Glaser, K. S., Pharmacological characterization of the pseudopterosins novel anti-inflammatory natural products isolated from the Caribbean soft coral, Pseudopterogorgia elisabethae, Pharmacol. Lett., 62, 401, 1998. 

Pseudopterosin A (129), which is a diterpene glycoside isolated from the sea whip Pseudopterogorgia elisabethae, shows anti-inflammatory activity by inhibiting release of leukotriene B2 from leukocytes (2, 35). A more interesting class of diter-penes includes sarcodictyn A (130) and elentherobin (131), which were isolated from the soft corals Sarcodictyon roseum and Eleutherobia sp., respectively. These diterpenoids show potent cytotoxicity by stabilizing microtnbnles (2, 35). 

Sanchez JA, Ortega-Barria E, Gonzalez J. New pseudopterosin 134. and seco-pseudopterosin diterpene glycosides from two Colombian isolates of Pseudopterogorgia elisabethae and their diverse biological activities. J. Nat. Prod. 2004 67 1672-1680. 

A few reports on anti-CMV compounds of marine origin belonging to other structural types have also been found in the literature. Examples included two plastoquinones isolated from the brown alga Sargassum micracanthum which was found to have potent antiviral activity against human CMV [114], and pseudopterosin P, Fig. (9) from the sea whip Pseudopterogorgia elisabethae [98]. 

Recently, Pseudopterosin C, a diterpene riboside isolated from the gorgonian corals Pseudopterogorgia bipinata and P. elisabethae [134] was launched by Estde Lauder as an additive to anti-aging cosmetics. It exhibits potent antiinflammatory and analgesic activities by reversibly affecting both, lipoxygenase and phospholipase A2 [135]. 

As we have discussed above, a significant fraction of Pseudopterogorgia metabolites have been evaluated in human disease-oriented in vitro testing programs. For instance, several major anti-inflammatory leads have emerged from work on Pseudopterogorgia corals. Most prominent are pseudopterostn A (1), pseudopterosin E... 

A comprehensive study of Pseudopterogorgia elisabethae from different regions of the Caribbean Sea and tropical Atlantic areas unveiled a novel class of compounds, known collectively as the pseudopterosins. Pseudopterosins are metabolites which contain diterpene glycoside moieties. Polyhydroxy steroids are another class of compounds commonly isolated from solvent extracts of this specie. 

From a taxonomically distinct and still unidentified specie of the Pseudopterogorgia genus, a related series of pseudopterosins containing bicyclic diterpenoid glycosides, 7 seco A-D, were also isolated and their structures elucidated by Look and Fenical [18]. Compounds 7 seco A-D possess potent anti-inflammatory and analgesic activities that are similar to the pseudopterosins, and also show antimicrobial activity towards the bacteria. Staphylococcus aureus. For example 7 seco-A, pseudopterosin exhibited a 69% reduction of inflammation in the mouse ear edema assay at a minimum inhibitory concentration (MIC) of 50 pg/ear. 

We presented a review of the natural product chemistry found in species of Pseudopterogorgia. These metabolites function as predator deterents and some of them proved to be (potential) therapeutic agents. The discovery of pseudopterosins and their potent anti-inflammatory activity should be especially highlighted as one of the most prominent (marine chemistry) scientific inventions of the last decade. We feel that the combination of the discoveries reviewed herein combined with drug design based on structure activity studies of these compounds will lead to therapeutic agents which although derived from marine life chemistry, will not rely on it as a source. 

Pseudopterosins. Diterpene glycosides (P A-L) from the sea whip Pseudopterogorgia elisabethae living in the tropical Atlantic. P occur as aglycones not only in the form shown but also as the 7)8-epimers and the enantiomers. The sugar residue at 0-8 or 0-9 can be D-xylo-, L-fuco-, and D-arabinopyranosyl which may be acetylated in the 2-, 3-, or 4-position. 

Look SA, Fenical W, Jacobs RS, Clardy J (1986) The pseudopterosins anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae. Proc Natl Acad Sci USA 83 6238-6240... 

Duque, C., Puyana, M., Narvaez, G., Osorno, O., Kara, N., and Fujimoto, Y. (2004) Pseudopterosins P-V, new compounds from the gorgonian octocoral Pseudopterogorgia elisabethae from Providencia islands, Colombian Caribbean. Tetrahedron, 60,10627-10635. 

Look, S.A. and Fenical, W. (1987) Seco-pseudopterosins, antiinflammatory diterpene-glycosides from gorgonians octocoral genus Pseudopterogorgia. Tetrahedron, 43, 3363-3370. 

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