Intramolecular Addition of the Riboflavin Side Chain

The presence of higher (> 0.2 M) concentrations of divalent anions A 2‐ (hydrogenphosphate, sulfate) is found to accelerate as well as to change entirely the course of riboflavin photolysis: instead of 10‐dealkylation to yield lumichrome, intramolecular addition of the 2′‐hydroxyl group is found to occur at the peri‐position C(9). The reaction is analogous to the “photohydration” of the flavin nucleus in the cationic state as described by Schöllnhammer and Hemmerich [ Eur. J. Biochem. (1974) 44 , 561–577]. The final product of the new addition reaction arises from autoxidation of a dihydroflavin intermediate and exhibits the structureIt is thus representative for a new class of flavins (“cyclo‐dehydroflavins”). Earlier reports on “anomalous” flavin photodegradation products absorbing around 410 nm [Holmström (1964) Ark. Kem. 22 , 281; Massey and Atherton (1962) J. Biol. Chem. 237 , 2965] are readily explained. The reaction is found to depend strictly on the presence of a nucleophilic function in the N(10)‐side chain, e.g. N(10)‐CH 2 ‐C(OH)RR′ or even N(10)‐(CH 2 ) 2 ‐SO − 3 . Quenching experiments suggest that the new reaction occurs via the singlet state 1 Fl* ox , while the normal photolysis is mediated by the triplet 3 Fl* ox . The new photoaddition is thought to occur via a Flavin‐A 2‐ complex which creates sterically favorable conditions for C(9)/O(2′α)‐interaction.