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 the presence of ammonia. The condensation reaction yields an α-aminonitrile, which is subsequently hydrolyzed to give the desired amino acid.[1][2] The method is used for the commercial production of racemic methionine from methional.[3]
Primary and secondary amines also give N-substituted amino acids. Likewise, the usage of ketones, instead of aldehydes, gives α,α-disubstituted amino acids.[4]
In the first part of the reaction, the carbonyl oxygen of an aldehyde is protonated, followed by a nucleophilic attack of ammonia to the carbonyl carbon. After subsequent proton exchange, water is cleaved from the iminium ion intermediate. A cyanide ion then attacks the iminium carbon yielding an aminonitrile.
Mechanism of the Strecker-Synthesis, part 1.
In the second part of the Strecker synthesis, 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.
Catalytic asymmetric Strecker reaction can be effected using thiourea-derived catalysts.[7] In 2012, a BINOL-derived catalyst was employed to generate chiral cyanide anion (see figure).[8]
The German chemist Adolph Strecker discovered the series of chemical reactions that produce an amino acid from an aldehydeorketone.[9][10] Using ammonia or ammonium salts in this reaction gives unsubstituted amino acids. In the original Strecker reaction acetaldehyde, ammonia, and hydrogen cyanide combined to form after hydrolysis alanine. Using primary and secondary amines in place of ammonium was shown to yield N-substituted amino acids.[10]
The classical Strecker synthesis gives racemic mixtures of α-amino acids as products, but several alternative procedures using asymmetric auxiliaries[11] or asymmetric catalysts[12][13] have been developed.
The asymmetric Strecker reaction was reported by Harada in 1963.[14] The first reported asymmetric synthesis via a chiral catalyst was published in 1996.[15] However, this was retracted in 2023.[16]
Several methods exist to synthesize amino acids aside from the Strecker synthesis.[17][3]
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 is an intermediate in one industrial synthesis of L-cysteine. Aspartic acid is produced by the addition of ammonia to fumarate using a lyase.[3]
^Davis, Franklin A.; Reddy, Rajarathnam E.; Portonovo, Padma S. (December 1994). "Asymmetric strecker synthesis using enantiopure sulfinimines: A convenient synthesis of α-amino acids". Tetrahedron Letters. 35 (50): 9351–9354. doi:10.1016/S0040-4039(00)78540-6.
^Ishitani, Haruro; Komiyama, Susumu; Hasegawa, Yoshiki; Kobayashi, Shū (February 2000). "Catalytic Asymmetric Strecker Synthesis. Preparation of Enantiomerically Pure α-Amino Acid Derivatives from Aldimines and Tributyltin Cyanide or Achiral Aldehydes, Amines, and Hydrogen Cyanide Using a Chiral Zirconium Catalyst". Journal of the American Chemical Society. 122 (5): 762–766. doi:10.1021/ja9935207.
^Huang, Jinkun; Corey, E. J. (December 2004). "A New Chiral Catalyst for the Enantioselective Strecker Synthesis of α-Amino Acids". Organic Letters. 6 (26): 5027–5029. doi:10.1021/ol047698w. PMID15606127.
^Iyer, Mani S.; Gigstad, Kenneth M.; Namdev, Nivedita D.; Lipton, Mark (January 1996). "Asymmetric Catalysis of the Strecker Amino Acid Synthesis by a Cyclic Dipeptide". Journal of the American Chemical Society. 118 (20): 4910–4911. doi:10.1021/ja952686e. PMID24178715.
^Duthaler, Rudolf O. (January 1994). "Recent developments in the stereoselective synthesis of α-aminoacids". Tetrahedron. 50 (6): 1539–1650. doi:10.1016/S0040-4020(01)80840-1.
