6-APA

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6-Aminopenicillanic acid
6-Aminopenicillanic acid.svg
6-Aminopenicillanic acid (6-APA).gif
Names
IUPAC name
6β-Amino-2,2-dimethylpenam-3α-carboxylic acid
Systematic IUPAC name
(2S,5R,6R)-6-Amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.008.177 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 208-993-4
PubChem CID
UNII
  • InChI=1S/C8H12N2O3S/c1-8(2)4(7(12)13)10-5(11)3(9)6(10)14-8/h3-4,6H,9H2,1-2H3,(H,12,13)/t3-,4+,6-/m1/s1 Yes check.svgY
    Key: NGHVIOIJCVXTGV-ALEPSDHESA-N Yes check.svgY
  • InChI=1/C8H12N2O3S/c1-8(2)4(7(12)13)10-5(11)3(9)6(10)14-8/h3-4,6H,9H2,1-2H3,(H,12,13)/t3-,4+,6-/m1/s1
    Key: NGHVIOIJCVXTGV-ALEPSDHEBW
  • O=C(O)[C@@H]1N2C(=O)[C@@H](N)[C@H]2SC1(C)C
Properties
C8H12N2O3S
Molar mass 216.26 g·mol−1
Appearancecolourless
Melting point 198 °C (388 °F; 471 K)
0.4 g/100 mL
log P 0.600
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

6-APA ((+)-6-aminopenicillanic acid) is a chemical compound used as an intermediate in the synthesis of β–lactam antibiotics. The major commercial source of 6-APA is still natural penicillin G: the semi-synthetic penicillins derived from 6-APA are also referred to as penicillins and are considered part of the penicillin family of antibiotics. [1]

In 1958, Beecham scientists from Brockham Park, Surrey, found a way to obtain 6-APA from penicillin. [2] Other β-lactam antibiotics could then be synthesized by attaching various side-chains to the nucleus. [3] The reason why this was achieved so many years after the commercial development of penicillin by Howard Florey and Ernst Chain lies in the fact that penicillin itself is very susceptible to hydrolysis, so direct replacement of the side-chain was not a practical route to other β-lactam antibiotics.[ citation needed ]

Related Research Articles

<span class="mw-page-title-main">Amoxicillin</span> Beta-lactam antibiotic

Amoxicillin is an antibiotic medication used to treat a number of bacterial infections. These include middle ear infection, strep throat, pneumonia, skin infections, and urinary tract infections among others. It is taken by mouth, or less commonly by injection.

<span class="mw-page-title-main">Beta-lactam</span> Family of chemical compounds

A beta-lactam (β-lactam) ring is a four-membered lactam. A lactam is a cyclic amide, and beta-lactams are named so because the nitrogen atom is attached to the β-carbon atom relative to the carbonyl. The simplest β-lactam possible is 2-azetidinone. β-lactams are significant structural units of medicines as manifested in many β-lactam antibiotics Up to 1970, most β-lactam research was concerned with the penicillin and cephalosporin groups, but since then, a wide variety of structures have been described.

<span class="mw-page-title-main">Beta-lactamase</span> Class of enzymes

Beta-lactamases, (β-lactamases) are enzymes produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties.

<span class="mw-page-title-main">Penicillin</span> Group of antibiotics derived from Penicillium fungi

Penicillins are a group of β-lactam antibiotics originally obtained from Penicillium moulds, principally P. chrysogenum and P. rubens. Most penicillins in clinical use are synthesised by P. chrysogenum using deep tank fermentation and then purified. A number of natural penicillins have been discovered, but only two purified compounds are in clinical use: penicillin G and penicillin V. Penicillins were among the first medications to be effective against many bacterial infections caused by staphylococci and streptococci. They are still widely used today for different bacterial infections, though many types of bacteria have developed resistance following extensive use.

<span class="mw-page-title-main">Beta-lactam antibiotics</span> Class of broad-spectrum antibiotics

β-lactam antibiotics are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and carbacephems. Most β-lactam antibiotics work by inhibiting cell wall biosynthesis in the bacterial organism and are the most widely used group of antibiotics. Until 2003, when measured by sales, more than half of all commercially available antibiotics in use were β-lactam compounds. The first β-lactam antibiotic discovered, penicillin, was isolated from a strain of Penicillium rubens.

<span class="mw-page-title-main">Methicillin</span> Antibiotic medication

Methicillin (USAN), also known as meticillin (INN), is a narrow-spectrum β-lactam antibiotic of the penicillin class.

<span class="mw-page-title-main">Cephalosporin</span> Class of pharmaceutical drugs

The cephalosporins are a class of β-lactam antibiotics originally derived from the fungus Acremonium, which was previously known as Cephalosporium.

<span class="mw-page-title-main">DD-transpeptidase</span>

DD-transpeptidase is a bacterial enzyme that catalyzes the transfer of the R-L-aca-D-alanyl moiety of R-L-aca-D-alanyl-D-alanine carbonyl donors to the γ-OH of their active-site serine and from this to a final acceptor. It is involved in bacterial cell wall biosynthesis, namely, the transpeptidation that crosslinks the peptide side chains of peptidoglycan strands.

A lactam is a cyclic amide, formally derived from an amino alkanoic acid. The term is a portmanteau of the words lactone + amide.

<span class="mw-page-title-main">Ticarcillin</span> Chemical compound

Ticarcillin is a carboxypenicillin. It can be sold and used in combination with clavulanate as ticarcillin/clavulanic acid. Because it is a penicillin, it also falls within the larger class of beta-lactam antibiotics. Its main clinical use is as an injectable antibiotic for the treatment of Gram-negative bacteria, particularly Pseudomonas aeruginosa and Proteus vulgaris. It is also one of the few antibiotics capable of treating Stenotrophomonas maltophilia infections.

<span class="mw-page-title-main">Flucloxacillin</span> Penicillin

Flucloxacillin, also known as floxacillin, is an antibiotic used to treat skin infections, external ear infections, infections of leg ulcers, diabetic foot infections, and infection of bone. It may be used together with other medications to treat pneumonia, and endocarditis. It may also be used prior to surgery to prevent Staphylococcus infections. It is not effective against methicillin-resistant Staphylococcus aureus (MRSA). It is taken by mouth or given by injection into a vein or muscle.

<span class="mw-page-title-main">Dicloxacillin</span> Chemical compound

Dicloxacillin is a narrow-spectrum β-lactam antibiotic of the penicillin class. It is used to treat infections caused by susceptible (non-resistant) Gram-positive bacteria. It is active against beta-lactamase-producing organisms such as Staphylococcus aureus, which would otherwise be resistant to most penicillins. Dicloxacillin is available under a variety of trade names including Diclocil (BMS).

<span class="mw-page-title-main">Penicillin-binding proteins</span> Class of proteins

Penicillin-binding proteins (PBPs) are a group of proteins that are characterized by their affinity for and binding of penicillin. They are a normal constituent of many bacteria; the name just reflects the way by which the protein was discovered. All β-lactam antibiotics bind to PBPs, which are essential for bacterial cell wall synthesis. PBPs are members of a subgroup of enzymes called transpeptidases. Specifically, PBPs are DD-transpeptidases.

<span class="mw-page-title-main">Oxacillin</span> Chemical compound

Oxacillin is a narrow-spectrum beta-lactam antibiotic of the penicillin class developed by Beecham.

<span class="mw-page-title-main">History of penicillin</span> Aspect of medical history

The history of penicillin follows observations and discoveries of evidence of antibiotic activity of the mould Penicillium that led to the development of penicillins that became the first widely used antibiotics. Following the production of a relatively pure compound in 1942, penicillin was the first naturally-derived antibiotic.

<span class="mw-page-title-main">Beecham Group</span> Former British pharmaceutical company (1859–1989)

The Beecham Group plc was a British pharmaceutical company. It was once a constituent of the FTSE 100 Index. Beecham, after having merged with American pharmaceutical company SmithKline Beckman to become SmithKline Beecham, merged with Glaxo Wellcome to become GlaxoSmithKline (GSK). GSK still uses the Beechams brand name in the UK for its over-the-counter cold and flu relief products.

<span class="mw-page-title-main">Thienamycin</span> Chemical compound

Thienamycin is one of the most potent naturally produced antibiotics known thus far, discovered in Streptomyces cattleya in 1976. Thienamycin has excellent activity against both Gram-positive and Gram-negative bacteria and is resistant to bacterial β-lactamase enzymes. Thienamycin is a zwitterion at pH 7.

<span class="mw-page-title-main">John C. Sheehan</span> American chemist (1915–1992)

John Clark Sheehan was an American organic chemist whose work on synthetic penicillin led to tailor-made forms of the drug. After nine years of hard work at the Massachusetts Institute of Technology (M.I.T.), he became the first to discover a practical method for synthesizing penicillin V. While achieving total synthesis, Sheehan also produced an intermediate compound, 6-aminopenicillanic acid, which turned out to be the foundation of hundreds of kinds of synthetic penicillin. Dr. Sheehan's research on synthetic penicillin paved the way for the development of customized forms of the lifesaving antibiotic that target specific bacteria. Over the four decades he worked at M.I.T., Sheehan came to hold over 30 patents, including the invention of ampicillin, a commonly used semi-synthetic penicillin that is taken orally rather than by injection. His research covered not only penicillin, but also peptides, other antibiotics, alkaloids, and steroids.

Cephalosporins are a broad class of bactericidal antibiotics that include the β-lactam ring and share a structural similarity and mechanism of action with other β-lactam antibiotics. The cephalosporins have the ability to kill bacteria by inhibiting essential steps in the bacterial cell wall synthesis which in the end results in osmotic lysis and death of the bacterial cell. Cephalosporins are widely used antibiotics because of their clinical efficiency and desirable safety profile.

Dr Frank Ralph Batchelor, known as Ralph, was a British biochemist and businessman.

References

  1. Patrick GL (2017). Medicinal Chemistry (6th ed.). Oxford, UK: Oxford University Press. p. 425. ISBN   978-0198749691.
  2. Batchelor, F. R.; Doyle, F. P.; Nayler, J. H. C.; Rolinson, G. N. (1959). "Synthesis of Penicillin: 6-Aminopenicillanic Acid in Penicillin Fermentations". Nature. 183 (4656): 257–258. Bibcode:1959Natur.183..257B. doi:10.1038/183257b0. PMID   13622762. S2CID   4268993.
  3. 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.