Occurrence
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Endiandric acid C was isolated from the Endiandra introsa tree is well characterized compound. People used the E. introsa tree for timber, for its fruit, drugs, spices, perfume oils, and leaves. The Greeks and Romans made wreathes for warriors and victorious athletes with E. intorsa leaves. The Endiadric acid c compound has more better antiobiotic activity better than ampicillin.
This genus of trees is also known as Lauraceae. These trees are found in the north-eastern Australian rainforests and other tropical and subtropical regions. However, these trees are also found in southern Canada and in Chile. Endiandric acid C is also isolated from E. xanthocarpa species. Endiandric acids are also found in Beilschmiedia trees, which were categorized under the Endiandra genus, but now forms its own genus as they found in cold, high laditude areas, and even in New Zealand. Other endiandric acids are found in the B. oligandra and B. anacardioides species, which are found in the Western Province of Cameroon.
Bioactivity
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This compounds has the best antibacterial activity in the Endiandrianic acid A-G compounds. Endiandric acid C was tested towards five strains of bacteria, which included Bacillus subtilis, Micococcus luteus, Streptococcus faecalis, Pseudomonas palida, and Escherichia coli through examining zone inhibition and minimum concentration, which was found to range between 0.24µg/mL and 500µg/mL. Endiandric acid C has also been used to cure uterine tumors, rubella, and female genital infections, and rheumatisms.
Biosynthesis
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Many biochemist predicted when examining K. C. Nicolaou’s biomimetic synthesis of the endiandric acid cascade that enzymes aided this reaction in the biosythesis. The biomimetic series determined that this process took place synthetically through a series of diels-alder cyclization reactions and therefore led researches to believe that diels-alderase assisted the formation of endiandric acid c. Although it has since then been discovered that many famous cyclization reactions like that of Lovastatin do result from the diels-alderase they have determine that the endiandric acid cascade does not involve enzymes but rather spontaneously undergoes ring formation from a derivative of bisnoryangorin 5, which results from both the shikimate and acetate pathways. The 4-hydroxycinnamoyl-CoA, compound 2, is the precursor that comes from the skimate pathway. Two units of malonyl CoA are then added to through the acetate pathway 3. Compound 3 is then reduced to the di-enol form that tautomerizes to give the bisnoryangorin 5. A small amount of compound 5 can be isolated, however SAM methylates most of it and gives yangorin 6. It has been proposed that a bisnoryangorin derivative 7, is then reduced by dehydrogenase to give the polyene precursor 8, that goes through spontaneous 8π conrotatory, 6π disrotatory, and [4+2] cyclization reactions to form endiandric acid c. This proposal is supported by the fact that Endiandric acids naturally occur as racemic mixtures and not in an enantiomerically pure form, which should happen if enzymes mediate this process. The diels-alder reaction itself is a powerful reaction that can give cyclic compounds with many stereogenic centers.
Organic Synthesis
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K. C. Nicolaou’s group successfully synthesized compound 1, in 1982 using a series of sterocontrolled electrocyclic reactions. They observe that the product looked like multiple endo-adducts resulting that came from several diels-alder reactions. They attempted to synthesize endiandric acid C from an acyclic symmetric diacetylenic diol precursor 14, which they hydrogenated using Lindlar’s catalyst to give 15. Compound 15 then goes through intramolecular [4+2] cycloadditions, 6π disrotatory, and 8π conrotatory cyclization to give compound 17, bicyclic diol. They then silylated compound 17 and reacted it with sodium cyanide and HMPA to give the cyanide intermediate 20, which was then hydrolyzed to the aldehyde form 21. Condensation of 21 gave the methyl ester compound 22. They reacted the methyl ester with the same reagent as intermediate 17 to give the methyl ester form of compound 28. They then treated Compound 28 with a lithio derivative of diethyl cinnamylphosphonate at -78 degrees Celsius, in THF for 15 minutes to give endiandric acid C 1.
References
editBandaranayake, W. M.; Banfield, J. E.; Black, D. S. C.; Fallon, G. D.; Gatehouse, B. M. Constituents of Endiandra-Spp 1. Endiandric-Acid a Novel Carboxylic-Acid from Endiandra-Introrsa Lauraceae and a Derived Lactone. Aust. J. of Chem. 1981, 34, 1655-1667.
Bandaranayake, W. M.; Banfield, J. E.; Black, D. S. C.; Fallon, G. D.; Gatehouse, B. M. Constituents of Endiandra Species. Iii. 4-[(E,E)-5'-Phenylpenta-2',4'-Dien-1'-Yl]Tetracyclo[5.4.0.02.5.03.9]Undec-10-Ene-8-Carboxylic Acid from Endiandra Introrsa (Lauraceae). Aust. J. of Chem. 1982, 35, 567-579.
Banfield, J. E.; Black, D. S. C.; Collins, D. J.; Hyland, B. P. M.; Lee, J. J.; Pranowo, S. R. Constituents of Some Species of Beilschmiedia and Endiandra (Lauraceae): New Endiandric Acid and Benzopyran Derivatives Isolated from B. Oligandra. Aust. J. of Chem. 1994, 47, 587-607.
Chouna, J. R.; Nkeng-Efouet, P. A.; Lenta, B. N.; Devkota, K. P.; Neumann, B.; Stammler, H.-G.; Kimbu, S. F.; Sewald, N. Antibacterial Endiandric Acid Derivatives from Beilschmiedia Anacardioides. Phytochemistry. 2009, 70, 684-688.
Gravel, E.; Poupon, E. Biogenesis and Biomimetic Chemistry: Can Complex Natural Products Be Assembled Spontaneously? Eur. J. Org. Chem. 2008, 27-42.
Miller, A. K.; Trauner, D. Mapping the Chemistry of Highly Unsaturated Pyrone Polyketides. Synlett 2006, 2295-2316.
Milne, B. F.; Long, P. F.; Starcevic, A.; Hranueli, D.; Jaspars, M. Spontaneity in the Patellamide Biosynthetic Pathway. Org. Biomol. Chem. 2006, 4, 631-638.
Nicolaou, K. C.; Petasis, N. A.; Uenishi, J.; Zipkin, R. E. The Endiandric Acid Cascade. Electrocyclizations in Organic Synthesis. 2. Stepwise, Stereocontrolled Total Synthesis of Endiandric Acids C-G. J. Am. Chem. Soc. 2002, 104, 5557-5558.
Nicolaou, K. C.; Petasis, N. A.; Zipkin, R. E. The Endiandric Acid Cascade. Electrocyclizations in Organic Synthesis. 4. Biomimetic Approach to Endiandric Acids a-G. Total Synthesis and Thermal Studies. J. Am. Chem. Soc. 1982, 104, 5560-5562.
Nicolaou, K. C.; Petasis, N. A.; Zipkin, R. E.; Uenishi, J. The Endiandric Acid Cascade. Electrocyclizations in Organic Synthesis. I. Stepwise, Stereocontrolled Total Synthesis of Endiandric Acids a and B. J. Am. Chem. Soc. 1982, 104, 5555-5557.
Nicolaou, K. C.; Zipkin, R. E.; Petasis, N. A. The Endiandric Acid Cascade. Electrocyclizations in Organic Synthesis. 3. "Biomimetic" Approach to Endiandric Acids a-G. Synthesis of Precursors. J. Am. Chem. Soc. 2002, 104, 5558-5560.
Oikawa, H. Involvement of the Diels-Alderases in the Biosynthesis of Natural Products. Bull. Chem. Soc. Jpn. 2005, 78, 537-554.
Gravel, E.; Poupon, E. Biogenesis and Biomimetic Chemistry: Can Complex Natural Products Be Assembled Spontaneously? Euro. J. O. C. 2008, 27-42.
Miller, A. K.; Trauner, D. Mapping the Chemistry of Highly Unsaturated Pyrone Polyketides. Synlett 2006, 2295-2316.
Milne, B. F.; Long, P. F.; Starcevic, A.; Hranueli, D.; Jaspars, M. Spontaneity in the Patellamide Biosynthetic Pathway. Organic & Biomolecular Chemistry 2006, 4, 631-638.
Nicolaou, K. C.; Petasis, N. A.; Zipkin, R. E. The Endiandric Acid Cascade. Electrocyclizations in Organic Synthesis. 4. Biomimetic Approach to Endiandric Acids a-G. Total Synthesis and Thermal Studies. Journal of the American Chemical Society 1982, 104, 5560-5562.