Strecker Synthesis of Amino Acids

Overview

• Strecker Synthesis is a two-step procedure for synthesizing amino acids.
• Involves the addition of cyanide ion to an imine, forming an alpha-amino nitrile, which is then hydrolyzed to give an alpha-amino acid.
• Allows synthesis of a variety of amino acids by varying the R group on the imine.

Mechanism

Part 1: Formation of Alpha-Amino Nitrile

• Cyanide ion acts as a nucleophile.
• Reacts with electrophiles such as imines, resulting in alpha-amino nitriles.
• Hydrolysis of alpha-amino nitriles with acid yields amino acids.
• Example: Synthesis of phenylalanine from aldehydes via imines.
• Original method used NH3 and HCN; safer method uses NH4Cl and KCN.
  • NH4Cl protonates aldehyde, activating it for NH3 attack.
  • Cyanide ion attacks imine to form the alpha-amino nitrile.

Part 2: Hydrolysis of Nitrile

• Involves protonation, attack of water, proton transfers, and elimination steps.
• Results in the formation of valine as a racemic mixture.

Applications

Synthesis of L-DOPA

• Important for treatment of Parkinson's disease.
• L-DOPA synthesized through hydroxylation of tyrosine in vivo.
• Chemically can be built via Strecker reaction starting from 3,4-dihydroxyphenylacetaldehyde.
• Results in a racemic mixture, resolved to obtain pure L-DOPA.

Other Applications

• Strecker synthesis can produce non-natural amino acids with unique properties (e.g., fluorescence, azides for click chemistry).
• Reaction is important in organic chemistry, capable of producing racemic mixtures.

Advances and Challenges

• Strecker has been modified to produce predominantly one enantiomer.
• Chiral auxiliaries and asymmetric catalytic approaches developed.
• Enantiomerically pure L-DOPA was achieved through catalytic hydrogenation (Nobel Prize-winning work).

Additional Notes

• Related to Kiliani-Fischer synthesis for sugar chain extension.
• Safer methods and handling of reagents like cyanide are emphasized.

References

• Original reaction by Adolf Strecker in 1850.
• Further developments and methods in synthetic organic chemistry.