The Bailey peptide synthesis is a

name reaction A name reaction is a chemical reaction named after its discoverers or developers. Among the tens of thousands of organic reactions that are known, hundreds of such reactions are well-known enough to be named after people. Well-known examples include ...

organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, ...

developed 1949 by J. L. Bailey. It is a method for the synthesis of a peptide from ''α''-amino acid-''N''-carboxylic acid anhydrides (NCAs) and amino acids or peptide esters.J. Leggett Bailey: ''A new Peptide Synthesis.'' In: ''

Nature Nature, in the broadest sense, is the physical world or universe. "Nature" can refer to the phenomena of the physical world, and also to life in general. The study of nature is a large, if not the only, part of science. Although humans are ...

.'' Band 164, Nr. 4177, 1949, S. 889, DOI:10.1038/164889a0. The reaction is characterized by short reaction times and a high yield of the target peptide. The reaction can be carried out at low temperatures in organic solvents. The residues R¹ and R² can be organic groups or hydrogen atoms, R³ is the used amino acid or peptide ester: UEV4 Bailey Peptid Synthese

Reaction mechanism

The reaction mechanism is not known in detail. Supposedly, the reaction begins with a nucleophilic attack of the amino group on the carbonyl carbon of the anhydride group of the N-carboxylic acid anhydride (1). After an intramolecular proton migration, a 1,4-proton shift and the cleavage of

carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...

follows, resulting in the peptide bond in the final product (2): RMV5 Bailey Peptid Synthese

Atom economy

The advantage in

atom economy Atom economy (atom efficiency/percentage) is the conversion efficiency of a chemical process in terms of all atoms involved and the desired products produced. The simplest definition was introduced by Barry Trost in 1991 and is equal to the ratio ...

of using NCAs for peptide formation is that there is no need for a protecting group on the functional group reacted with the amino acid.Ryoichi Katakai: ''Peptide Synthesis Using o-Nitrophenylsulfenyl N-Carboxy α-Amino Acid Anhydrides.'' In: ''The Journal of Organic Chemistry.'', Band 40, Nr. 19, 1975, S. 2697–2702, DOI:10.1021/jo00907a001. For example, the Merrifield synthesis depends on the use of Boc and Bzl

protecting groups A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In man ...

, which need be removed after the reaction. In the case of Bailey peptide synthesis, the free peptide is directly obtained after the reaction. However, unwanted and difficult to remove

by-products A by-product or byproduct is a secondary product derived from a production process, manufacturing process or chemical reaction; it is not the primary product or service being produced. A by-product can be useful and marketable or it can be consid ...

may be formed. An ''N''-substitution of the NCA (for example, by an ''o''-nitrophenylsulfenyl group) can simplify the subsequent purification process, but on the other hand deteriorates the atom economy of the reaction. The synthesis of NCAs can be carried out by the Leuchs reactionHans Rytger Kricheldorf: ''α-Aminoacid-N-Carboxy-Anhydrides and Related Heterocycles. Syntheses, Properties, Peptide Synthesis, Polymerization.'' Springer Verlag, Berlin Heidelberg, 1987, S. 1–4, DOI: 10.1007/978-3-642-71586-0, (Druck), (Online). or by the reaction of ''N''-(benzyloxycarbonyl)-amino acids with

oxalyl chloride Oxalyl chloride is an organic chemical compound with the formula (COCl)2. This colorless, sharp-smelling liquid, the diacyl chloride of oxalic acid, is a useful reagent in organic synthesis. Preparation Oxalyl chloride was first prepared in 1892 ...

.D. Konopinska, I.Z. Siemion: ''Synthesis of N-Carboxy-α-amino Acid Anhydrides.'' In: ''Angewandte Chemie International Edition.'' Band 6, Nr. 3, 1967, S. 248, DOI:10.1002/anie.196702481. In the latter case, again the procedure is less efficient in the sense of atom economy.

Synthesized peptides

The following peptides were synthesized using this method by 1949:
* DL-

Ala Ala, ALA, Alaa or Alae may refer to: Places * Ala, Hiiu County, Estonia, a village * Ala, Valga County, Estonia, a village * Ala, Alappuzha, Kerala, India, a village * Ala, Iran, a village in Semnan Province * Ala, Gotland, Sweden * Alad, S ...

Gly Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid (carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinogeni ...

* L- Tyr-

* DL- Tyr- Tyr * DL-

-DL-

* DL-di-

-L- cystinyl-di-

* DL-

-L- Tyr-

* DL-

-L- Tyr-

* DL-

-DL-

-L- Tyr-

* L- Tyr-L- Tyr-L- Tyr * L- Cystinyl-di-

Literature

* P. Katsoyannis: ''The Chemistry of Polypeptides.'' Springer Science & Business Media, 2012, {{ISBN, 978-1-461-34571-8, S. 129.

References

Biochemistry Name reactions