6-aminopenicillanic acid

Structural formula
General
Surname	6-aminopenicillanic acid
other names	(2 S , 5 R , 6 R ) -6-Amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo [3.2.0] heptane-2-carboxylic acid
Molecular formula	C 8 H 12 N 2 O 3 S
Brief description	beige solid
External identifiers / databases
EC number	208-993-4
ECHA InfoCard	100.008.177
PubChem	11082
Wikidata	Q2823234
properties
Molar mass	216.26 g mol −1
Physical state	firmly
Melting point	198–200 ° C (decomposition); about 205 ° C (decomposition);
solubility	sparingly soluble in water (2.46 g l −1 at 20 ° C)
safety instructions
GHS labeling of hazardous substances	no GHS pictograms
	no GHS pictograms
H and P phrases	H: no H-phrases
	P: no P-phrases
Toxicological data	> 2000 mg kg −1 ( LD 50 , rat , oral ) ; > 1000 mg kg −1 ( LD 50 , mouse , intraperitoneal ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

In the 6-aminopenicillanic acid (6-APA) is the basic building blocks of penicillins . With the help of 6-APA and a precursor (coupling piece), all semisynthetic penicillins such as B. ampicillin or amoxicillin can be produced. 6-APA was described and patent pending by GN Rolinson in 1958.

synthesis

6-APA is both chemically and enzymatically by hydrolysis of Penicillin G prepared. During enzymatic hydrolysis, penicillin G reacts with water to form 6-APA and phenylacetic acid . Chemical hydrolysis takes place at low temperatures with trimethylchlorosilane , phosphorus pentachloride and dichloromethane . The enzymatic hydrolysis takes place with the penicillin G acylase . Due to the highly reactive, difficult to store and toxic substances as well as the required temperatures of −50 ° C, biotechnological production with penicillin G acylase is preferred. The yield of both methods is between 80 and 90%.

Individual evidence

↑ ^a ^b ^c ^d ^e ^f ^g ^h data sheet (+) - 6- Aminopenicillanic acid, 96% Template: Linktext-Check / Escaped from Sigma-Aldrich , accessed on March 1, 2016 ( PDF ).
↑ European Pharmacopoeia , Deutscher Apotheker Verlag Stuttgart, 6th edition, 2008, p. 527, ISBN 978-3-7692-3962-1 .
^ FR Batchelor, FP Doyle, JHC Nayler, GN Rolinson: Synthesis of Penicillin: 6-Aminopenicillanic Acid in Penicillin Fermentations . In: Nature . tape 183 , no. 4656 , January 24, 1959, p. 257-258 , doi : 10.1038 / 183257b0 .
↑ GN Rolinson, AM Geddes: The 50th anniversary of the discovery of 6-aminopenicillanic acid (6-APA). In: International journal of antimicrobial agents. Volume 29, number 1, January 2007, pp. 3–8, doi: 10.1016 / j.ijantimicag.2006.09.003 . PMID 17137753 .
↑ Patent US2941995 : Recovery of solid 6-aminopenicillanic acid. Filed July 22, 1958 , published June 21, 1960 , Applicant: Beecham Research Laboratories, Inventor: Frank Peter Doyle, John Herbert Charles Nayler, George Newbolt Rolinson. ‌
^ A. Nandi, S. Pan, R. Potumarthi, MK Danquah, IP Sarethy: A Proposal for Six Sigma Integration for Large-Scale Production of Penicillin G and Subsequent Conversion to 6-APA. In: Journal of analytical methods in chemistry. 2014, p. 413616, doi: 10.1155 / 2014/413616 . PMID 25057428 , PMC 4099176 (free full text).
↑ A. Brugging, EC Roos, E. de Vroom: Penicillin acylase in the industrial production of β-lactam antibiotics. In: Organic Process Research and Development. 2 (2), 1998, pp. 128-133.
↑ K. Srirangan, V. Orr, L. Akawi, A. Westbrook, M. Moo-Young, CP Chou: Biotechnological advances on penicillin G acylase: pharmaceutical implications, unique expression mechanism and production strategies. In: Biotechnology Advances . Volume 31, number 8, December 2013, pp. 1319-1332, doi: 10.1016 / j.biotechadv.2013.05.006 . PMID 23721991 .
^ RP Elander: Industrial production of beta-lactam antibiotics. In: Applied Microbiology and Biotechnology . Volume 61, Numbers 5-6, June 2003, pp. 385-392, doi: 10.1007 / s00253-003-1274-y . PMID 12679848 .

[Sigma-1] ↑ ^a ^b ^c ^d ^e ^f ^g ^h data sheet (+) - 6- Aminopenicillanic acid, 96% Template: Linktext-Check / Escaped from Sigma-Aldrich , accessed on March 1, 2016 ( PDF ).

[EuropäischesArzneibuch-2] European Pharmacopoeia , Deutscher Apotheker Verlag Stuttgart, 6th edition, 2008, p. 527, ISBN 978-3-7692-3962-1 .

[3] FR Batchelor, FP Doyle, JHC Nayler, GN Rolinson: Synthesis of Penicillin: 6-Aminopenicillanic Acid in Penicillin Fermentations . In: Nature . tape 183 , no. 4656 , January 24, 1959, p. 257-258 , doi : 10.1038 / 183257b0 .

[4] GN Rolinson, AM Geddes: The 50th anniversary of the discovery of 6-aminopenicillanic acid (6-APA). In: International journal of antimicrobial agents. Volume 29, number 1, January 2007, pp. 3–8, doi: 10.1016 / j.ijantimicag.2006.09.003 . PMID 17137753 .

[5] Patent US2941995 : Recovery of solid 6-aminopenicillanic acid. Filed July 22, 1958 , published June 21, 1960 , Applicant: Beecham Research Laboratories, Inventor: Frank Peter Doyle, John Herbert Charles Nayler, George Newbolt Rolinson. ‌

[6] A. Nandi, S. Pan, R. Potumarthi, MK Danquah, IP Sarethy: A Proposal for Six Sigma Integration for Large-Scale Production of Penicillin G and Subsequent Conversion to 6-APA. In: Journal of analytical methods in chemistry. 2014, p. 413616, doi: 10.1155 / 2014/413616 . PMID 25057428 , PMC 4099176 (free full text).

[7] A. Brugging, EC Roos, E. de Vroom: Penicillin acylase in the industrial production of β-lactam antibiotics. In: Organic Process Research and Development. 2 (2), 1998, pp. 128-133.

[8] K. Srirangan, V. Orr, L. Akawi, A. Westbrook, M. Moo-Young, CP Chou: Biotechnological advances on penicillin G acylase: pharmaceutical implications, unique expression mechanism and production strategies. In: Biotechnology Advances . Volume 31, number 8, December 2013, pp. 1319-1332, doi: 10.1016 / j.biotechadv.2013.05.006 . PMID 23721991 .

[9] RP Elander: Industrial production of beta-lactam antibiotics. In: Applied Microbiology and Biotechnology . Volume 61, Numbers 5-6, June 2003, pp. 385-392, doi: 10.1007 / s00253-003-1274-y . PMID 12679848 .