Strecker amino acid synthesis

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Strecker synthesis
Named after Adolph Strecker
Reaction type Substitution reaction
Identifiers
Organic Chemistry Portal strecker-synthesis
RSC ontology ID RXNO:0000207

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]

Reaction mechanism

In the first part of the reaction, the

iminium ion
intermediate. A cyanide ion then attacks the iminium carbon yielding an aminonitrile.

Mechanism of the Strecker-Synthesis, part 1.
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.

Mechanism of the Strecker synthesis
Mechanism of the Strecker synthesis

Asymmetric Strecker reactions

One example of the Strecker synthesis is a multikilogram scale synthesis of an

L-valine derivative starting from Methyl isopropyl ketone:[5]

(CH3)2CHC(O)CH3 + HCN + NH3 → (CH3)2CHC(CN)(NH2)CH3 + H2O

The initial reaction product of 3-methyl-2butanone with

(S)-alpha-phenylethylamine as chiral auxiliary the ultimate reaction product was chiral alanine.[6]

Catalytic asymmetric Strecker synthesis. The catalyst 1a is based on chiral 1,1′-Bi-2-naphthol (BINOL), the "R" indicating the chirality. "Boc" is tert-Butyloxycarbonyl protecting group.

Catalytic asymmetric Strecker reaction can be effected using thiourea-derived

BINOL-derived catalyst was employed to generate chiral cyanide anion (see figure).[8]

History

The German chemist Adolph Strecker discovered the series of chemical reactions that produce an amino acid from an aldehyde or ketone.[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.

chiral catalyst was published in 1996.[15] However, this was retracted in 2023.[16]

Commercial syntheses of amino acids

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.

fumarate using a lyase.[3]

References

  1. doi:10.15227/orgsyn.009.0004
    .
  2. doi:10.15227/orgsyn.011.0004
    .
  3. ^
    ISBN 978-3527306732
    .
  4. PMID 12733893
    .
  5. PMID 17713956
    .
  6. PMID 21851054
    .
  7. PMID 19829379
    .
  8. PMID 23169053
    .
  9. doi:10.1002/jlac.18500750103
    .
  10. ^
    doi:10.1002/jlac.18540910309
    .
  11. doi:10.1016/S0040-4039(00)78540-6
    .
  12. doi:10.1021/ja9935207
    .
  13. PMID 15606127
    .
  14. S2CID 43857409
    .
  15. PMID 24178715
    .
  16. ISSN 0002-7863
    .
  17. doi:10.1016/S0040-4020(01)80840-1
    .

See also
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