Prephenic acid

Occurrence and biological significance

Prephenic acid occurs naturally as an intermediate in the biosynthesis of phenylalanine and tyrosine via the shikimic acid pathway. It is formed from chorismic acid by chorismate mutase:

The biosynthesis involves a [3,3]-sigmatropic Claisen rearrangement of chorismic acid.{{cite journal

:[[Image:Prephenate biosynthesis.png|350px]]

Prephenic acid can be dehydrated by prephenate dehydratase to phenylpyruvic acid, which is a precursor of phenylalanine.

Alternatively, it can be decarboxylated and oxidised by prephenate dehydrogenase to give 4-hydroxyphenylpyruvic acid, which is a precursor of tyrosine:

Synthesis

Prephenic acid is unstable; as a 1,4-cyclohexadiene, it is easily aromatized, for example, under the influence of acids or bases. This instability makes both isolation and synthesis difficult. Prephenic acid was first isolated from mutants of Escherichia coli that were unable to convert prephenic acid to phenylpyruvic acid. During this process, the barium salt was obtained.

Stereochemistry

Prephenic acid is an example of achiral (optically inactive) molecule which has two pseudoasymmetric atoms (i.e. stereogenic but not chirotopic centers), the C1 and the C4 cyclohexadiene ring atoms. It has been shown that of the two possible diastereoisomers, the natural prephenic acid is one that has both substituents at higher priority (according to CIP rules) on the two pseudoasymmetric carbons, i.e. the carboxyl and the hydroxyl groups, in the cis configuration, or (1s,4s) according to the new IUPAC stereochemistry rules (2013).

The other stereoisomer, i.e. trans or, better, (1r,4r), is called epiprephenic.

References

References

1. Richard G.H. Cotton, Frank Gibson. (April 1965). "The biosynthesis of phenylalanine and tyrosine; enzymes converting chorismic acid into prephenic acid and their relationships to prephenate dehydratase and prephenate dehydrogenase".
2. H. Plieninger. (July 1962). "Prephenic Acid: Properties and the Present Status of its Synthesis".
3. (November 2000). "A strategically positioned cation is crucial for efficient catalysis by chorismate mutase". The Journal of Biological Chemistry.
4. {{KEGG enzyme. 4.2.1.51
5. (1965). "The biosynthesis of phenylalanine and tyrosine; enzymes converting chorismic acid into prephenic acid and their relationships to prephenate dehydratase and prephenate dehydrogenase". Biochim. Biophys. Acta.
6. (1966). "Aromatic metabolism in plants. I. A study of the prephenate dehydrogenase from bean plants". Biochim. Biophys. Acta.
7. (1979-11-01). "Synthesis of disodium prephenate and disodium epiprephenate. Stereochemistry of prephenic acid and an observation on the base-catalyzed rearrangement of prephenic acid to p-hydroxyphenyllactic acid". Journal of the American Chemical Society.
8. (2013-12-17). "Nomenclature of Organic Chemistry".