Prephenic acid, commonly also known by its

anionic An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

form prephenate, is an intermediate in the

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

of the aromatic

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the chemical formula, formula . It can be viewed as a benzyl group substituent, substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of ...

and

tyrosine -Tyrosine or tyrosine (symbol Tyr or Y) or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is ...

, as well as of a large number of

secondary metabolites Secondary metabolites, also called ''specialised metabolites'', ''secondary products'', or ''natural products'', are organic compounds produced by any lifeform, e.g. bacteria, archaea, fungi, animals, or plants, which are not directly involved ...

of the

shikimate pathway The shikimate pathway (shikimic acid pathway) is a seven-step metabolic pathway used by bacteria, archaea, fungi, algae, some protozoans, and plants for the biosynthesis of folates and aromatic amino acids (tryptophan, phenylalanine, and tyrosine) ...

Occurrence and biological significance

Prephenic acid occurs naturally as an intermediate in the

and

via the shikimic acid pathway. It is formed from

chorismic acid Chorismic acid, more commonly known as its ion, anionic form chorismate, is an important biochemical intermediate in plants and microorganisms. It is a precursor for: * The aromatic amino acids phenylalanine, tryptophan, and tyrosine * Indole, ind ...

by chorismate mutase. It can be

dehydrated In physiology, dehydration is a lack of total body water that disrupts Metabolism, metabolic processes. It occurs when free water loss exceeds intake, often resulting from excessive sweating, health conditions, or inadequate consumption of wate ...

by prephenate dehydratase to

phenylpyruvic acid Phenylpyruvic acid is the organic compound with the formula C6H5CH2C(O)CO2H. It is a keto acid. Occurrence and properties The compound exists in equilibrium with its (''E'')- and (''Z'')-enol tautomers. It is a product from the oxidative deamin ...

, which is a precursor of phenylalanine. Alternatively, it can be dehydrated by prephenate dehydrogenase to 4-hydroxyphenylpyruvic acid, which is a precursor of tyrosine. It is biosynthesized by a ,3 sigmatropic

Claisen rearrangement The Claisen rearrangement is a powerful carbon–carbon chemical bond, bond-forming chemical reaction discovered by Rainer Ludwig Claisen. The heating of an allyl Vinyl group, vinyl ether will initiate a Sigmatropic reaction, ,3sigmatropic r ...

chorismate Chorismic acid, more commonly known as its anionic form chorismate, is an important biochemical intermediate in plants and microorganisms. It is a precursor for: * The aromatic amino acids phenylalanine, tryptophan, and tyrosine * Indole, indole d ...

. :

Synthesis

Prephenic acid is unstable; as a

1,4-cyclohexadiene 1,4-Cyclohexadiene is an organic compound with the formula C6H8. It is a colourless, flammable liquid that is of academic interest as a prototype of a large class of related compounds called terpenoids, an example being γ-terpinene. An isomer of ...

, 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 ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'' that were unable to convert prephenic acid to

. During this process, the

barium Barium is a chemical element; it has symbol Ba and atomic number 56. It is the fifth element in group 2 and is a soft, silvery alkaline earth metal. Because of its high chemical reactivity, barium is never found in nature as a free element. Th ...

salt was obtained.

Stereochemistry

Prephenic acid is an example of achiral (optically inactive) molecule which has two pseudoasymmetric atoms (''i.e.''

stereogenic In stereochemistry, a stereocenter of a molecule is an atom (center), axis or plane that is the focus of stereoisomerism; that is, when having at least three different groups bound to the stereocenter, interchanging any two different groups cr ...

but not chirotopic centers), the C1 and the C4

cyclohexadiene Cyclohexadiene may refer to: * Cyclohexa-1,3-diene, * Cyclohexa-1,4-diene, See also

* Benzene or its theoretical isomer ''1,3,5-Cyclohexatriene'' * Cyclohexene {{chemistry index ...

ring atoms. It has been shown that of the two possible

diastereoisomers In stereochemistry, diastereomers (sometimes called diastereoisomers) are a type of stereoisomer. Diastereomers are defined as non-mirror image, non-identical stereoisomers. Hence, they occur when two or more stereoisomers of a compound have dif ...

, 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 (1''s'',4''s'') according to the new IUPAC stereochemistry rules (2013). The other stereoisomer, ''i.e. trans'' or, better, (1''r'',4''r''), is called epiprephenic.

References

{{Reflist Hydroxy acids Alpha-keto acids Dicarboxylic acids Cyclohexadienes