Photolabile Precursors of Biological Amides: Synthesis and Characterization of Caged o-Nitrobenzyl Derivatives of Glutamine, Asparagine, Glycinamide, and γ-Aminobutyramide

Article abstract of DOI:10.1021/jo00069a021

The synthesis and photochemical properties of o-nitrobenzyl derivatives of glutamine, asparagine, glycinamide, and γ-aminobutyramide (GABA amide) linked through the amide nitrogen are reported.The time scale for the release of the amides from the photolabile o-nitrobenzyl protecting group was unknown and has now been investigated.The compounds are photolyzed by UV irradiation at 308 and 350 nm to release free amino acid amide and the presumed aromatic nitroso side product, with quantum yields in the range of 0.13 for the methyl derivative of glutamine (20) to 0.24 for the carboxy derivative of glutamine (21).Both pH and the α-substituent of the o-nitrobenzyl protecting group affect the rate of the photolysis reaction which is initiated by a single laser pulse at 308 nm and monitored by the optical absorbance decay time course of the transient aci-nitro anion intermediate.The rate of disappearance of this intermediate, assumed to reflect the appearance of products, is influenced by pH and the α-substituent attached to the benzylic carbon.For example, the rates for the α-carboxyl (21) and α-H (19) derivatives of glutamine increase by a factor of 50 as the pH is lowered from 11.5 to 5.5, whereas the rate for the α-methyl derivative (20) shows a minimum at pH 9.5.The half lives of the aci-nitro intermediates of the α-methyl, α-carboxyl, and α-H derivatives of glutamine at pH 7.5 are 360, 720, and 1800 μs, respectively.