Pyroglutamic acid

Structural formula
	D -pyroglutamic acid (top) and L -pyroglutamic acid (bottom)
General
Surname	Pyroglutamic acid
other names	Pidolic acid; PCA; 5-oxoproline; L -pyroglutamic acid; ( S ) -pyroglutamic acid; D -pyroglutamic acid; ( R ) -pyroglutamic acid;
Molecular formula	C 5 H 7 NO 3
External identifiers / databases
EC number	223-735-0
ECHA InfoCard	100,021,578
PubChem	439685
ChemSpider	388752
DrugBank	DB03088
Wikidata	Q421383
properties
Molar mass	129.11 g mol −1
Physical state	firmly
Melting point	162–163 ° C ( L -enantiomer)
solubility	soluble in water, ethanol and acetone
safety instructions
GHS labeling of hazardous substances danger
H and P phrases	H: 318
	P: 280-305 + 351 + 338-310
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Pyroglutamic acid or pidolic acid is a derivative of glutamic acid and is not a (proteinogenic) amino acid . Pyroglutamic acid has a stereogenic center in the 2-position on the pyrrolidine ring, so it is chiral . There are thus two enantiomers: L -pyroglutamic acid [synonym: ( S ) -pyroglutamic acid] and D -pyroglutamic acid [synonym: ( R ) -pyroglutamic acid].

Whenever “pyroglutamic acid” is mentioned in this article or in the scientific literature without any additional name ( prefix ), L- pyroglutamic acid is meant.

Occurrence

L -pyroglutamic acid is a cyclized inner amide of L -glutamic acid and is found in vegetables, fruits, grasses and molasses. Peptides with N -terminal L -glutamine, the amino function of which is unprotected, are easily converted into pyroglutamyl peptides. In the human body, for example, it occurs in the peptide hormone gonadoliberin , which is formed in the hypothalamus .

Extraction and presentation

When a mixture of equal parts by weight of glutamic acid and water is heated in an autoclave, pyroglutamic acid is obtained at reaction temperatures of 135-140 ° C. with elimination of water .

Chemical properties

The carboxy group of L- pyroglutamic acid can be esterified with alcohols in an acid medium to form L- pyroglutamic acid esters (together with the salts of pyroglutamic acid also referred to as pyroglutamates ), the lactam function remains unchanged. Treatment with phosphorus pentasulfide converts the lactam function of the L -pyroglutamic acid ester into a thiolactam function.

D - and also L pyroglutamic acid are not to amino acids , because next to the acidic carboxyl group no basic amino group in the molecule is present, since the nitrogen in the five-membered ring part of a lactam (cyclic amide is). At the same time, D - and L - pyroglutamic acid are derivatives of an amino acid, D - or L - glutamic acid . Pyroglutamic acid at the N terminus of a protein is a typical block in Edman degradation , which means that the N terminus has to be cleaved off beforehand.

use

The pure enantiomers of pyroglutamic acid, i.e. L- pyroglutamic acid and D -pyroglutamic acid, are often used for the resolution of racemic amines. From L pyroglutamic acid also can be L - proline synthesis. The chiral auxiliary RAMP was synthesized from D -pyroglutamic acid. The use of both enantiomers of pyroglutamic acid in further stereoselective syntheses was described in a review article. The natural product domoic acid was synthesized from ( S ) -pyroglutamic acid in a multi-step synthesis .

Individual evidence

↑ ^a ^b ^c ^d The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition, 2006, p. 1373, ISBN 978-0-911910-00-1 .
↑ ^a ^b Safety Data Sheet , Iris Biotech , accessed on November 28, 2017.
↑ Hans-Dieter Jakubke and Hans Jeschkeit: Amino acids, peptides, proteins. Verlag Chemie, 1982, p. 139, ISBN 3-527-25892-2 .
↑ Axel Kleemann, Jürgen Martens and Karlheinz Drauz: Synthesis of proline from glutamic acid , Chemiker-Zeitung 105 (1981) 266.
^ Karlheinz Drauz, Axel Kleemann , Jürgen Martens , Paul Scherberich and Franz Effenberger (1986): Amino Acids 7. A Novel Synthetic Route to L- Proline. In: J. Org. Chem. Vol. 51, pp. 3494-3498. doi : 10.1021 / jo00368a019
↑ Dieter Enders, Herbert Eichenauer and Reimund Pieter: Enantioselective synthesis of (-) - ( R ) - and (+) - ( S ) - [6] -Gingerol - spice principle of ginger , Chemical Reports 112 (1979) 3703-3714. doi : 10.1002 / cber.19791121118 .
↑ Carmen Nájera and Miguel Yus: Pyroglutamic acid: a versatile building block in asymmetric synthesis , In: Tetrahedron: Asymmetry 10 (1999) 2245-2303, doi : 10.1016 / S0957-4166 (99) 00213-X .
↑ Yasufumi Ohfune, Masako Tomita: Total synthesis of (-) - domoic acid. A revision of the original structure. In: Journal of the American Chemical Society. 104, 1982, pp. 3511-3513, doi : 10.1021 / ja00376a048 .

[Merck_index-1] The Merck Index. An Encyclopaedia of Chemicals, Drugs and Biologicals. 14th edition, 2006, p. 1373, ISBN 978-0-911910-00-1 .

[Iris-2] Safety Data Sheet , Iris Biotech , accessed on November 28, 2017.

[Jakubke-3] Hans-Dieter Jakubke and Hans Jeschkeit: Amino acids, peptides, proteins. Verlag Chemie, 1982, p. 139, ISBN 3-527-25892-2 .

[Kleemann-4] Axel Kleemann, Jürgen Martens and Karlheinz Drauz: Synthesis of proline from glutamic acid , Chemiker-Zeitung 105 (1981) 266.

[Drauz-5] Karlheinz Drauz, Axel Kleemann , Jürgen Martens , Paul Scherberich and Franz Effenberger (1986): Amino Acids 7. A Novel Synthetic Route to L- Proline. In: J. Org. Chem. Vol. 51, pp. 3494-3498. doi : 10.1021 / jo00368a019

[Enders_et_al.-6] Dieter Enders, Herbert Eichenauer and Reimund Pieter: Enantioselective synthesis of (-) - ( R ) - and (+) - ( S ) - [6] -Gingerol - spice principle of ginger , Chemical Reports 112 (1979) 3703-3714. doi : 10.1002 / cber.19791121118 .

[Nájera-7] Carmen Nájera and Miguel Yus: Pyroglutamic acid: a versatile building block in asymmetric synthesis , In: Tetrahedron: Asymmetry 10 (1999) 2245-2303, doi : 10.1016 / S0957-4166 (99) 00213-X .

[Ohfune-8] Yasufumi Ohfune, Masako Tomita: Total synthesis of (-) - domoic acid. A revision of the original structure. In: Journal of the American Chemical Society. 104, 1982, pp. 3511-3513, doi : 10.1021 / ja00376a048 .