text: -Photo-leucine resembles -leucine in its structure. However, the latter contains a photo-activatable diazirine ring, which the former does not, and which yields a reactive carbene after the light-induced loss of nitrogen, fact that confers -photo-leucine its properties. This photo-reactive amino acid is synthesized by α-bromination of the azi-carboxylic acid followed by aminolysis of azi-bromo-carboxylic acid.
  The classic procedure for synthesizing photo-leucine is based on the following steps:
  *4,4-azi-pentanoic acid, CCl and thionyl chloride are heated to 65 °C for 30 minutes. Then, N-bromosuccinimide, CCl and 48% HBr are added and the mixture is stirred at 55 °C for 4 hours. The solvent and free bromine are removed under reduced pressure and the residue is extracted with 50 mL CCl. The solvent is removed and the crude product (2-bromo-4,4-azi-pentanoyl chloride) dissolved in acetone and hydrolyzed with aqueous NaHCO. The crude brominated free acid is obtained upon acidification with HCl and extraction with dichloromethane. The solvent is removed and the product filtered through silica gel in isohexane acetate followed by the removal of the solvent. Following this procedure, we are able to add a diazirine ring to the 4,4-azi-pentanoic acid, and to obtain finally the -2-bromo-4,4-azi-pentanoic acid.
  *Aminolysis of -2-bromo-4,4-azi-pentanoic acid is performed in ammonia-saturated methanol and 25% aq ammonia for 5 days at 55 °C. After evaporation of the ammonia, 20 mL of concentrated HCl are added followed by evaporation of the water at reduced pressure. The dry residue is extracted with 20 mL hot methanol and the extract neutralized with N,N-dimetylethylamine. Upon standing for 2 days at -32 °C a precipitate formed which is isolated and re-crystallized twice from 70% ethanol to yield pure -2-amino-4,4-azi-pentonoic acid.
  *-2-amino-4,4-azi-pentonoic acid is acetylated to obtain acetylation -2-acetamino-4,4-azi-pentanoic acid followed by enzymatic deacetylation to give pure -2-amino-4,4'-azi-pentanoic acid, also known as -photo-leucine.
  Recently, synthesis of photo-leucine has been improved. This new way of synthesizing photo-leucine requires boc-(S)-photo-leucine, which is prepared via ozonolysis of a commercially available product, followed by formation of the diazirine by de method of Church and Weiss. 
  This route supposes a significant improvement over the original six-step synthesis of (S)-photo-leucine, which proceeded in low yield and required enzymatic resolution of a racemic intermediate.