Amino acid ''N''-carboxyanhydrides, also called Leuchs' anhydrides, are a family of

heterocyclic A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

s derived from

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...

s. They are white, moisture-reactive solids. They have been evaluated for applications the field of

biomaterials A biomaterial is a substance that has been engineered to interact with biological systems for a medical purpose, either a therapeutic (treat, augment, repair, or replace a tissue function of the body) or a diagnostic one. As a science, biomateria ...

Preparation

140px, Glycine N-carboxyanhydride is the parent member of the amino acid N-carboxyanhydrides. NCAs are typically prepared by

phosgenation Phosgene is the organic chemical compound with the formula COCl2. It is a toxic, colorless gas; in low concentrations, its musty odor resembles that of freshly cut hay or grass. Phosgene is a valued and important industrial building block, esp ...

s: They were first synthesized by Hermann Leuchs by heating an ''N''-ethoxycarbonyl or ''N''-methoxycarbonyl

chloride in a vacuum at 50-70 °C: A moisture-tolerant route to unprotected NCAs employs

epoxide In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale ...

s as scavengers of hydrogen chloride. This synthesis of NCAs is sometimes called the . The relatively high temperatures necessary for this cyclization results in the decomposition of several NCAs. Of several improvements, one notable procedure involves treating an unprotected amino acid with phosgene or its trimer.

Reactions

NCAs are prone to hydrolysis to the parent amino acid: :RCHNHC(O)OC(O) + H₂O → H₂NCH(R)CO₂H + CO₂ Some derivatives however tolerate water briefly. NCAs convert to homopolypeptides ( (H)CH(R)CO)sub>n) through ring-opening polymerization: :nRCHNHC(O)OC(O) → (H)CH(R)CO)sub>n + nCO₂ Poly-L-lysine has been prepared from ''N''-carbobenzyloxy-α-''N''-carboxy-L-lysine anhydride, followed by

deprotection 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 ...

with

phosphonium iodide Phosphonium iodide is a chemical compound with the formula . It is an example of a salt containing an unsubstituted phosphonium cation (). Phosphonium iodide is commonly used as storage for phosphine and as a reagent for substituting phosphorus int ...

Peptide synthesis In organic chemistry, peptide synthesis is the production of peptides, compounds where multiple amino acids are linked via amide bonds, also known as peptide bonds. Peptides are chemically synthesized by the condensation reaction of the carboxyl ...

from NCAs does not require protection of the amino acid

functional group In organic chemistry, a functional group is a substituent or moiety in a molecule that causes the molecule's characteristic chemical reactions. The same functional group will undergo the same or similar chemical reactions regardless of the re ...

s. N-Substituted NCAs, such as sulfenamide derivatives have also been examined. The

ring-opening polymerization In polymer chemistry, ring-opening polymerization (ROP) is a form of chain-growth polymerization, in which the terminus of a polymer chain attacks cyclic monomers to form a longer polymer (see figure). The reactive center can be radical, anion ...

of NCAs is catalyzed by metal

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

s. The polymerization of NCA’s have been considered as a prebiotic route to polypeptides.

References

{{Reflist Organic chemistry Organic reactions

Preparation

Reactions

Further reading

See also

References