6-APA ((+)-6-aminopenicillanic acid) is an

organic compound Some chemical authorities define an organic compound as a chemical compound that contains a carbon–hydrogen or carbon–carbon bond; others consider an organic compound to be any chemical compound that contains carbon. For example, carbon-co ...

that is used in the synthesis of β–lactam antibiotics including

amoxicillin Amoxicillin is an antibiotic medication belonging to the aminopenicillin class of the penicillin family. The drug is used to treat bacterial infections such as middle ear infection, strep throat, pneumonia, skin infections, odontogenic inf ...

ampicillin Ampicillin is an antibiotic belonging to the aminopenicillin class of the penicillin family. The drug is used to prevent and treat several bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, s ...

oxacillin Oxacillin (trade name Bactocill) is a narrow-spectrum second-generation beta-lactam antibiotic of the penicillin class developed by Beecham. It was patented in 1960 and approved for medical use in 1962. Medical uses Oxacillin is a penicill ...

, and

carbenicillin Carbenicillin is a bactericidal antibiotic belonging to the carboxypenicillin subgroup of the penicillins. It was discovered by scientists at Beecham and marketed as Pyopen. It has Gram-negative coverage which includes ''Pseudomonas aeruginosa' ...

. The major commercial source of 6-APA is natural penicillin G, which contains an N-phenylacetyl substituent. The semi-synthetic penicillins derived from 6-APA are also referred to as penicillins and are considered part of the penicillin family of antibiotics.

History

In 1958, Beecham scientists from Brockham Park,

Surrey Surrey () is a Ceremonial counties of England, ceremonial county in South East England. It is bordered by Greater London to the northeast, Kent to the east, East Sussex, East and West Sussex to the south, and Hampshire and Berkshire to the wes ...

, found a way to obtain 6-APA from

penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...

. Other β-lactam antibiotics could then be synthesized by attaching various side-chains to the nucleus.F.P. Doyle, J.H.C. Nayler, G.N. Rolinson ''US Patent 2,941,995'', filed July 22, 1958, granted June 21, 1960. Recovery of solid 6-aminopenicillanic acid. The reason why this was achieved so many years after the commercial development of penicillin by

Howard Florey Howard Walter Florey, Baron Florey, (; 24 September 1898 – 21 February 1968) was an Australian pharmacologist and pathologist who shared the Nobel Prize in Physiology or Medicine in 1945 with Ernst Chain and Sir Alexander Fleming for his ro ...

and

Ernst Chain Sir Ernst Boris Chain (19 June 1906 – 12 August 1979) was a German-born British biochemist and co-recipient of the Nobel Prize in Physiology or Medicine for his work on penicillin. Life and career Chain was born in Berlin, the son of Marg ...

lies in the fact that penicillin itself is very susceptible to

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

, so direct replacement of the side-chain was not a practical route to other β-lactam antibiotics.{{cn, date=March 2023

References

Beta-lactam antibiotics Sulfur heterocycles Amines