Corey's synthesis of pentacycloanammoxic acid

Background

        Fatty acid based derivatives of this target compound are major components of organelles in anammoxic microbes. These microbes use hydrazine and nitrite as intermediates en route to the production of energy. This is extraordinary because hydrazine is a major component of rocket fuel!

Purpose of Synthesis

        It is known that the anammoxic microbes contain this acid, however the specific mechanism of this compound is unknown in the cell. Another component to the cloud of mystery that surrounds this compound is how the microbes themselves biosynthesize it. The five cyclobutane rings are all anti to each other, and the biological pathway to this highly strained target needs to be pinned down. Understanding this biological synthesis could lend itself to more general methods of overcoming high thermodynamic barriers. An obvious way to make the pentacyclododecane system would be to adjoin two hexatriene molecules together. However, this would require 19.6 kcal/mol! So, by understanding how the microbes can do this might be instrumental in overcoming all sorts of thermodynamic synthetic obstacles.

The Synthesis

        The synthesis starts out using cyclooctatetraene, which is cheap, and very readily availible. It is also very easily functionalized. Corey has devised a linear synthesis for the target, and although it successfully produces the acid, there is only about a 1% overall yield. This low overall yield is attributed to the second step of the third reaction sequence, when the ring flip occurs in acetonitrile. There is only a 6% yield in this one step.

References

1. Mascitti, V.; Corey, E. J. Total Synthesis of (±)-Pentacycloanammoxic Acid, J. Am. Chem. Soc. 2004 126(48); 15664-15665. DOI: 10.1021/ja044089a
2. Mascitti, V.; Corey, E. J. Enantioselective Synthesis of Pentacycloanammoxic Acid, J. Am. Chem. Soc. 2006 128(10) pp 3118 - 3119. DOI: 10.1021/ja058370g