Endiandric acid C

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 0.24 μg/mL and 500 μg/mL.

[citation needed] 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.[citation needed] 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.

K. C. Nicolaou's group successfully synthesized endiandric acid, 1, in 1982 as a test of Black's biosynthetic conjecture,[1][2] using a biomimetic strategy involving series of stereocontrolled electrocyclic reactions.

Protection of a single alcohol moiety (as TBDPS) was accomplished using the silyl chloride via the corresponding tricyclic iodoether intermediate (not shown), with the internally masked remaining hydroxyl group being released on treatment with zinc dust in acetic acid (giving 18 in 70-80% yield).

Bromination of the alcohol under Appel conditions followed by its displacement on treatment with sodium cyanide in HMPA gave nitrile 20, the key intermediate in all of this group's endiandric acid syntheses.

Proposed course of reactions in nature, resulting in endiandric acid C. [ citation needed ]
Reaction sequence accounting for precursor of the tetraene structure required for biosynthesis of endiandric acids. [ citation needed ]
Reaction sequence in Nicolaou's 1982 biomimetic total synthesis of endiandric acid C. [ citation needed ]
Initial electrocyclizations in Nicolaou endiandric acid C synthesis, to provide diol 17 shown in the main scheme. This key intermediate is then ready for elaboration into the olefin which can undergo the further 6π[4+2] ( Diels-Alder ) cycloaddition reaction shown in the main scheme, to provide the title natural product. [ citation needed ]