Prephenic acid
{{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 = (1s,4s)-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=
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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.{{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}}{{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}} It is formed from chorismic acid by chorismate mutase. It can be dehydrated by prephenate dehydratase to phenylpyruvic acid, 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 [3,3]-sigmatropic Claisen rearrangement of chorismate.{{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
| 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}}
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{{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|issn=0002-7863}} 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).{{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}}
The other stereoisomer, i.e. trans or, better, (1r,4r), is called epiprephenic.