text: Many biochemists predicted when examining K. C. Nicolaou's biomimetic synthesis of the endiandric acid cascade that enzymes aided this reaction in the biosynthesis.  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 been discovered since then 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 bisnoryangonin 5, which results from both the shikimate and acetic pathways.  The 4-hydroxycinnamoyl-CoA, compound 2, is the precursor that comes from the shikimate 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 bisnoryangonin 5.  A small amount of compound 5 can be isolated, however S-adenosyl methionine methylates most of it and gives yangonin 6.  It has been proposed that a bisnoryangonin 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.