{{chembox | Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 464214063 | ImageFile = Prephenic acid.svg | ImageSize = 150px | ImageFile1 = Prephenic-acid-based-on-PDB-3ZP7-3D-bs-17.png | ImageSize1 = 150px | PIN = (1''s'',4''s'')-1-(2-Carboxy-2-oxoethyl)-4-hydroxycyclohexa-2,5-diene-1-carboxylic acid | OtherNames = Prephenate; ''cis''-1-Carboxy-4-hydroxy-α-oxo-2,5-cyclohexadiene-1-propanoic acid |Section1={{Chembox Identifiers | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 16735981 | InChI = 1/C10H10O6/c11-6-1-3-10(4-2-6,9(15)16)5-7(12)8(13)14/h1-4,6,11H,5H2,(H,13,14)(H,15,16)/t6-,10+ | InChIKey = FPWMCUPFBRFMLH-XGAOUMNUBN | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C10H10O6/c11-6-1-3-10(4-2-6,9(15)16)5-7(12)8(13)14/h1-4,6,11H,5H2,(H,13,14)(H,15,16)/t6-,10+ | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = FPWMCUPFBRFMLH-XGAOUMNUSA-N | CASNo = 126-49-8 | CASNo_Ref = {{cascite|correct|CAS}} | CASNo_Comment = (unspecified) | CASNo1 = 87664-40-2 | CASNo1_Ref = {{cascite|correct|CAS}} | CASNo1_Comment = (''cis'') | UNII_Ref = {{fdacite|correct|FDA}} | UNII = Z66B98Z97I | UNII_Comment = (unspecified) | PubChem = 1028 | PubChem_Comment = (unspecified) | ChEBI_Ref = {{ebicite|changed|EBI}} | ChEBI = 84387 | SMILES = O=C(O)[C@@]/1(CC(=O)C(O)=O)\C=C/[C@@H](O)\C=C\1 | MeSHName = Prephenic+acid }} |Section2={{Chembox Properties | C=10 | H=10 | O=6 | Appearance= | Density= | MeltingPt= | BoilingPt= | Solubility= }} }}

'''Prephenic acid''', commonly also known by its anionic form '''prephenate''', is an intermediate in the biosynthesis of the aromatic amino acids phenylalanine and tyrosine, as well as of a large number of secondary metabolites of the shikimate pathway.

== Occurrence and biological significance == Prephenic acid occurs naturally as an intermediate in the biosynthesis of phenylalanine and tyrosine via the shikimic acid pathway.<ref name=":0">{{citation|author=Richard G.H. Cotton, Frank Gibson |date=April 1965 |doi=10.1016/0304-4165(65)90429-0 |issue=1 |pages=76–88 |periodical=Biochimica et Biophysica Acta (BBA) - General Subjects |title=The biosynthesis of phenylalanine and tyrosine; enzymes converting chorismic acid into prephenic acid and their relationships to prephenate dehydratase and prephenate dehydrogenase |volume=100|pmid=14323651 }}<!-- auto-translated from German by Module:CS1 translator --></ref><ref name=":1">{{citation|author=H. Plieninger |date=July 1962 |doi=10.1002/anie.196203671 |issue=7 |pages=367–372 |periodical=Angewandte Chemie International Edition in English |title=Prephenic Acid: Properties and the Present Status of its Synthesis |volume=1}}<!-- auto-translated from German by Module:CS1 translator --></ref> It is formed from chorismic acid by chorismate mutase:<ref>{{cite journal |vauthors = Kast P, Grisostomi C, Chen IA, Li S, Krengel U, Xue Y, Hilvert D |title = A strategically positioned cation is crucial for efficient catalysis by chorismate mutase |journal = The Journal of Biological Chemistry |volume = 275 |issue = 47 |pages = 36832–8 |date = November 2000 |pmid = 10960481 |doi = 10.1074/jbc.M006351200 |doi-access = free }}</ref>

The biosynthesis involves a [3,3]-sigmatropic Claisen rearrangement of chorismic acid.<ref>{{cite journal | title = On the mechanism of the chorismate mutase reaction |author = Helmut Goerisch |journal = Biochemistry | year = 1978 |pages = 3700–3705 |doi = 10.1021/bi00611a004 |volume = 17 |issue = 18| pmid = 100134 }}</ref><ref>{{cite journal | title = Thermodynamics of the Conversion of Chorismate to Prephenate: Experimental Results and Theoretical Predictions |author = Peter Kast, Yadu B. Tewari, Olaf Wiest, Donald Hilvert, Kendall N. Houk, and Robert N. Goldberg |journal = J. Phys. Chem. B |volume = 101 |issue = 50 |pages = 10976–10982 | year = 1997 |doi = 10.1021/jp972501l}}</ref>

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Prephenic acid can be dehydrated by prephenate dehydratase to phenylpyruvic acid, which is a precursor of phenylalanine.<ref>{{KEGG enzyme|4.2.1.51}}</ref><ref>{{cite journal | vauthors = Cotton RG, Gibson F | title = The biosynthesis of phenylalanine and tyrosine; enzymes converting chorismic acid into prephenic acid and their relationships to prephenate dehydratase and prephenate dehydrogenase | date = 1965 | journal = Biochim. Biophys. Acta | volume = 100 | pages = 76&ndash;88 | pmid = 14323651 | doi=10.1016/0304-4165(65)90429-0}}</ref>

{{chemrxn|width=40%| {{chemrxn/cpd|prephenic acid }} {{chemrxn/arw|direction=reversible|fwd_out={{chem2|CO2 + H2O}}|rev_in={{chem2|CO2 + H2O}} }} {{chemrxn/cpd|phenylpyruvic acid }} }}

Alternatively, it can be decarboxylated and oxidised by prephenate dehydrogenase to give 4-hydroxyphenylpyruvic acid, which is a precursor of tyrosine:<ref name=":0" /><ref>{{cite journal |vauthors=Gamborg OL, Keeley FW | date = 1966 | title = Aromatic metabolism in plants. I. A study of the prephenate dehydrogenase from bean plants | journal = Biochim. Biophys. Acta | volume = 115 | pages = 65&ndash;72 | pmid = 4379953 | issue = 1 | doi=10.1016/0304-4165(66)90049-3}}</ref>

{{chemrxn|width=50%| {{chemrxn/cpd|Prephenic acid|caption=prephenic acid }} {{chemrxn/txt|+ NADP<sup>+</sup>}} {{chemrxn/arw|direction=reversible|fwd_out={{chem2|CO2 + H+}}|rev_in={{chem2|CO2 + H+}} }} {{chemrxn/cpd|4-Hydroxyphenylpyruvic acid|caption=4-hydroxyphenylpyruvic acid }} {{chemrxn/txt|+ NADPH}} }}

== 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.<ref name=":1" />

== 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<ref>{{Cite journal|last1=Danishefsky|first1=Samuel|last2=Hirama|first2=Masahiro|last3=Fritsch|first3=Nancy|last4=Clardy|first4=Jon|date=1979-11-01|title=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=Journal of the American Chemical Society|volume=101|issue=23|pages=7013–7018|doi=10.1021/ja00517a039|bibcode=1979JAChS.101.7013D |issn=0002-7863}}</ref> 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 (1''s'',4''s'') according to the new IUPAC stereochemistry rules (2013).<ref>{{Cite book|title=Nomenclature of Organic Chemistry|last1=Favre|first1=Henri A|last2=Powell|first2=Warren H|date=2013-12-17|isbn=9780854041824|language=en|doi=10.1039/9781849733069}}</ref>

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

==See also== * C<sub>10</sub>H<sub>10</sub>O<sub>6</sub>

==References== {{Reflist}}

Category:Hydroxycarboxylic acids Category:Alpha-keto acids Category:Dicarboxylic acids Category:Cyclohexadienes