Elenic acid

In 1995, Scheuer and coworkers isolated and characterized elenic acid (153, Figure 6.15), an inhibitor of topoisomerase II, from the Indonesian sponge, Plakimstrella sp. Elenic acid has a unique structure, in which its phenol portion and P, y-unsaturated carboxylic acid moiety are linked with a long polymethylene... 

Besides typical cardanol-like structure, Sleeper and Fenical have identified in 1977 navenone, an alkylphenol derivative as a component of trail pheromone of the mollusk Navanax inermis [27]. Another alkylpheno lie derivative, plakinidone, has beed isolated in 1991 from a Caribbean sponge Plakortis angulospiculatus [26]. In 1995 the carboxylic acid derivative of alkylphenol - elenic acid was isolated from the Indonesian sponge Plakinastrella [25]. The structures and formulas of known monohydric phenolic lipids are presented in Fig. (1). 

Apart from cardanol (Fig. 1-1,2,4, and 5) which collectively is a minor natural component in Anacardium occidentale, the first 3-substituted monohydric phenols isolated were, ginkgol (identical with cardanol monene), (depicted in Fig. 1-2), from Ginkgo biloba, and camnospermanol, (Fig. 1-6), from Camnospermum auriculata. More recently a number of 4-substituted monohydric phenols, (depicted in Fig.l), have been obtained from natural sources including, elenic acid, R-2,4-dimethyl-22-(4-hydroxyphenyl)-docos-3(E)-enoic acid, 7, navenone,... 

Elenic acid, 7, was isolated from an Indonesian sponge Plakinastrella sp. [25]. It is an enzyme inhibitor of DNA topoisomerase II with an IC50 of 0.1pg/ml [25] and also a potent inhibitor of calf DNA polymerase a and rat DNA polymerases P [250]. Elenic acid was found not to bind to DNA directly and did not affect the activities of plant DNA polymerases I and II, prokaryotic DNA polymerases such as Escherichia coli DNA polymerase I or other DNA metabolic enzymes, for example, HIV reverse transcriptase, T7 RNA polymerase and bovine deoxyribonuclease I. 

Elenic acid did not prevent the growth of NUGC-3 cancer cells and the LD50 was 22.5p.M. 

Another way to generated vinyl alanes is the transition metal catalyzed addition of trialkylaluminum reagents to alkynes. In Hoye s synthesis of elenic acid, 10 1-dodecyne was treated with Me3Al in the present of Cp2ZrCl2 and then MeLi. The resulting ate complex 730 was then reacted with triflate 731 to give a 96% yield of the alkene, 732. 

Takanashi, S., TakagL M., Taldkawa, H., and Mori, K. (1998) Synthesis of elenic acid, an inhibitor of topoisomerase II from the sponge Plakinastrella sp. J. Chem. Soc. Perkin Trans. 1,1603—1606. 

Juagdan, E.G., Kalidindi, R.S., Scheuer, P.J., and Kelly-Borges, M. (1995) Elenic acid, an inhibitor of topoisomerase II, from a sponge Plakinastrella sp. Tetrahedron Lett., 36, 2905-2908. 

Elenic acid (Figure 1) was isolated from an Indonesian sponge, an undescribed species of Plakinastrella. Its structure, a C22 fatty acid with a phenol terminus, is remarkably unspectacular. With only two functionalized and widely separated termini the compound can easily be manipulated synthetically for discovery of its active moiety. Its topoisomerase II activity, 0.1 pg/mL, compares favorably with currently used clinical agents, as e.g. doxorubicin or etoposide. ... 

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