The Strecker amino acid synthesis, also known simply as the Strecker synthesis, is a method for the synthesis of amino acids by the reaction of an aldehyde with
cyanide
In chemistry, cyanide () is an inorganic chemical compound that contains a functional group. This group, known as the cyano group, consists of a carbon atom triple-bonded to a nitrogen atom.
Ionic cyanides contain the cyanide anion . This a ...
in the presence of
ammonia
Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...
. The
condensation reaction
In organic chemistry, a condensation reaction is a type of chemical reaction in which two molecules are combined to form a single molecule, usually with the loss of a small molecule such as water. If water is lost, the reaction is also known as a ...
yields an α-aminonitrile, which is subsequently hydrolyzed to give the desired amino acid. The method is used for the commercial production of racemic
methionine
Methionine (symbol Met or M) () is an essential amino acid in humans.
As the precursor of other non-essential amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine play ...
from
methional
Methional is an organic compound with the formula CH3SCH2CH2CHO. It is a colorless liquid that is a degradation product of methionine. It is a notable flavor in potato-based snacks, namely potato chips, one of the most popular foods containing met ...
.
[
Primary and secondary amines also give N-substituted amino acids. Likewise, the usage of ]ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
s, instead of aldehydes, gives α,α-disubstituted amino acids.
Reaction mechanism
In the first part of the reaction process, the carbonyl
In organic chemistry, a carbonyl group is a functional group with the formula , composed of a carbon atom double bond, double-bonded to an oxygen atom, and it is divalent at the C atom. It is common to several classes of organic compounds (such a ...
is converted to an iminium
In organic chemistry, an iminium cation is a polyatomic ion with the general structure . They are common in synthetic chemistry and biology.
Structure
Iminium cations adopt alkene-like geometries: the central C=N unit is nearly coplanar with a ...
, to which a cyanide ion adds. First, the carbonyl oxygen of an aldehyde
In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...
is protonated, followed by a nucleophilic attack
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they a ...
of ammonia to the carbonyl carbon. After subsequent proton exchange, water is cleaved to form the iminium ion intermediate. A cyanide ion then attacks the iminium carbon yielding an aminonitrile.
In the second part of the reaction process, the nitrile is hydrolyzed
Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile.
Biological hydrolysi ...
. First, the nitrile nitrogen of the aminonitrile is protonated, and the nitrile carbon is attacked by a water molecule. A 1,2-diamino-diol is then formed after proton exchange and a nucleophilic attack of water to the former nitrile carbon. Ammonia is subsequently eliminated after the protonation of the amino group, and finally the deprotonation of a hydroxyl group produces an amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
.
Asymmetric Strecker reactions
One example of the Strecker synthesis is a multikilogram scale synthesis of an L-valine derivative starting from Methyl isopropyl ketone:
:
The initial reaction product of 3-methyl-2butanone with sodium cyanide
Sodium cyanide is a compound with the formula Na C N and the structure . It is a white, water-soluble solid. Cyanide has a high affinity for metals, which leads to the high toxicity of this salt. Its main application, in gold mining, also expl ...
and ammonia
Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...
is resolved by application of L-tartaric acid. In contrast, asymmetric Strecker reactions require no resolving agent. By replacing ammonia with (S)-alpha-phenylethylamine as chiral auxiliary
In stereochemistry, a chiral auxiliary is a Stereogenic center, stereogenic group or unit that is temporarily incorporated into an organic compound in order to control the stereochemical outcome of the synthesis. The chirality present in the auxil ...
the ultimate reaction product was chiral alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group sid ...
.
Catalytic asymmetric Strecker reaction can be effected using thiourea
Thiourea () is an organosulfur compound with the formula and the structure . It is structurally similar to urea (), with the oxygen atom replaced by sulfur atom (as implied by the '' thio-'' prefix). The properties of urea and thiourea differ s ...
-derived catalyst
Catalysis () is the increase in rate of a chemical reaction due to an added substance known as a catalyst (). Catalysts are not consumed by the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recycles quick ...
s. In 2012, a BINOL-derived catalyst was employed to generate chiral cyanide anion (see figure).
History
The German chemist Adolph Strecker
Adolph Strecker (21 October 1822 – 7 November 1871) was a German chemist who is known primarily for his work with amino acids.
Life and work
Strecker was born in Darmstadt, the son of Friedrich Ludwig Strecker, an archivist working for the h ...
discovered the series of chemical reaction
A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...
s that produce an amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
from an aldehyde
In organic chemistry, an aldehyde () (lat. ''al''cohol ''dehyd''rogenatum, dehydrogenated alcohol) is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred ...
or ketone
In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...
. Using ammonia or ammonium salts in this reaction gives unsubstituted amino acids. In the original Strecker reaction acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic compound, organic chemical compound with the chemical formula, formula , sometimes abbreviated as . It is a colorless liquid or gas, boiling near room temperature. It is one of the most ...
, ammonia
Ammonia is an inorganic chemical compound of nitrogen and hydrogen with the chemical formula, formula . A Binary compounds of hydrogen, stable binary hydride and the simplest pnictogen hydride, ammonia is a colourless gas with a distinctive pu ...
, and hydrogen cyanide
Hydrogen cyanide (formerly known as prussic acid) is a chemical compound with the chemical formula, formula HCN and structural formula . It is a highly toxic and flammable liquid that boiling, boils slightly above room temperature, at . HCN is ...
combined to form after hydrolysis alanine
Alanine (symbol Ala or A), or α-alanine, is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a carboxylic acid group, both attached to the central carbon atom which also carries a methyl group sid ...
. Using primary and secondary amines in place of ammonium was shown to yield N-substituted amino acids.[
The classical Strecker synthesis gives ]racemic mixture
In chemistry, a racemic mixture or racemate () is a mixture that has equal amounts (50:50) of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as r ...
s of α-amino acids as products, but several alternative procedures using asymmetric auxiliaries or asymmetric catalysts have been developed.
The asymmetric Strecker reaction was reported by Harada in 1963. The first reported asymmetric synthesis via a chiral catalyst was published in 1996. However, this was retracted in 2023.
Commercial syntheses of amino acids
Several methods exist to synthesize amino acids aside from the Strecker synthesis.[
The commercial production of amino acids, however, usually relies on mutant bacteria that overproduce individual amino acids using glucose as a carbon source. Otherwise amino acids are produced by enzymatic conversions of synthetic intermediates. ]2-Aminothiazoline-4-carboxylic acid
2-Aminothiazoline-4-carboxylic acid (ACTA) is the organosulfur compound and a heterocycle with the formula HO2CCHCH2SCNH2N. This derivative of thiazoline is an intermediate in the industrial synthesis of L-cysteine, an amino acid
Amino a ...
is an intermediate in one industrial synthesis of L-cysteine
Cysteine (; symbol Cys or C) is a semiessential proteinogenic amino acid with the chemical formula, formula . The thiol side chain in cysteine enables the formation of Disulfide, disulfide bonds, and often participates in enzymatic reactions as ...
. Aspartic acid
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids, i.e., the building blocks of protei ...
is produced by the addition of ammonia to fumarate
Fumaric acid or ''trans''-butenedioic acid is an organic compound with the formula HO2CCH=CHCO2H. A white solid, fumaric acid occurs widely in nature. It has a fruit-like taste and has been used as a food additive. Its E number is E297.
The sa ...
using a lyase.
References
See also
* Bucherer–Bergs reaction
The Bucherer–Bergs reaction is the chemical reaction of carbonyl compounds (aldehydes or ketones) or cyanohydrins with ammonium carbonate and potassium cyanide to give hydantoins. The reaction is named after Hans Theodor Bucherer.
Reaction me ...
{{Authority control
Multiple component reactions
Substitution reactions
Name reactions
Chemical synthesis of amino acids