Tyrosine reaction with nitrous acid

The synthesis of a structurally somewhat more complex indolone tyrosine kinase inhibitor starts with the construction of the pyrrole ring. Reaction of tert-butyl acetoacetate (87) with nitrous acid leads to nitrosa-tion on the activated methylene carbon. This reaction introduces the nitrogen atom that will appear in the target pyrrole. Condensation of 88 with... 

Much of Landsteiner s pioneer work was carried out with haptens that were aromatic amines. The compounds were converted to diazonium salts with nitrous acid and aUowed to react with proteins at alkaline pH (approximately 9). Reaction occurred primarily with histidine, tyrosine, and tryptophan residues of the protein carrier. For a representative procedure, see Kabat (p. 799 seq.). An interesting application of this procedure was the preparation of a chloramphenicol-protein conjugate which was used to elicit antibodies specific for chloramphenicol. In this case, a prior reduction of the nitro group of chloramphenicol to an amino group was required. As early as 1937, carcinogenic compounds were conjugated to protein carriers by means of their isocyanate derivatives which were prepared from amines. Immune sera were raised, and their properties were studied. - ... 

The reaction of sRNA with formaldehyde was studied by Marini (83) and also by Tissiferes (84)- The latter found the reactivity to be such as to suggest intramolecular hydrogen-bonding between different strands of RNA. Marini found that reaction with formaldehyde, as well as that with nitrous acid and with glyoxal, affected different amino acid acceptor activities to different extents (tyrosine and isoleucine being generally least affected), which indicates that the specificity for different amino acids resides in different nucleotide sequences of the respective RNA molecules. 

Xanthoprotein reactions are given by proteins with aromatic side groups On addition of nitric acid, the product turns yellow and, after further addition of ammonia, orange. The Millon reaction is specific for tyrosine On boiling, e.g., egg-white solution with a solution of mercury in nitric-acid containing nitrous acid, a red-brown precipitate is formed. 

Excess tyrosine in the serum and urine can be detected by chromatography. It can be measured fluorimetrically in serum by its reaction with a-nitroso-jS-naphthol and nitrite in the presence of nitric acid. Tyrosine can be detected in urine by the Millon reaction when it gives a red colour with mercuric nitrate in nitric acid containing a trace of nitrous acid. 

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