SENSITIZED PHOTOOXIDATION OF HISTIDINE AND ITS DERIVATIVES . PRODUCTS AND MECHANISM OF REACTION

In connection with the chemical modification of protein, the photooxidation of histidine and N-benzoylhistidine was investigated. It was confirmed that histidine is photooxidized to aspartic acid and urea via several intermediate compounds. The isolation of the intermediates as pure compounds, however, was difficult because of their instability during the purification. In the photooxidation of N-benzoylhistidine also, besides the final products, many kinds of intermediate products were detected and among them 17 compounds were isolated in pure state and characterized. The structures of five compounds were determined, and those of other five compounds were proposed. The same products were obtained when riboflavin or rose bengal instead of methylene blue was used as the photosensitizer in the photooxidation of N-benzoylhistidine though their relative yields were slightly different. The reaction of the photooxidation of N-benzoylhistidine was explained by the following proposed mechanism given in Scheme I. Thus, the substrate was first converted into a cyclo peroxide by a 1,4-cycloaddition of the singlet oxygen. The cyclo peroxide ring then was ruptured to give the hydroxyl compounds such as XXI and XXII. The subsequent nucleophilic additions at the C4 or C5 position of XXI or XXII, respectively, gave several intermediate compounds such as, III and XXIII, or dimers; XV (XVI) or XI (XII). Further photooxidation of the N-benzoylhistidine moiety of some of these dimers might give rise to monomeric compounds which were finally converted into N-benzoylaspartic acid and N-benzoylasparagine, as is discussed in the text. © 1969, American Chemical Society. All rights reserved.