Coenzyme models. Part 45. Synthesis of atropisomeric flavins and their novel redox-induced racemisation

Abstract

Seven (5-carba)isoalloxazines with restricted rotation about the C(1′)–N(10) single bond were synthesized for the first time. They were optically resolved by a liquid chromatographic method. Six of these atropisomers (92.1–100% enantiomeric excess)(e.e.) did not racemise thermally (at 70 °C) or by visible light irradiation (at 30 °C). On the other hand, the (5-carba)isoalloxazines with a 2′-substituted phenyl group or a naphthyl group at N (10) racemised invariably when they were reduced to 1,5-dihydro forms [by four different reducing agents including photoreduction with ethylene diamine tetra-acetic acid (EDTA)]. The kinetic studies confirm that the racemisation process consists of slow, ratedetermining reduction of chiral (5-carba)isoalloxazines followed by rapid rotation of the C(1′)–N(10) single bond. The easy rotation in the reduced state is due to conversion of the ‘planar’ oxidised forms into the ‘bent’ reduced forms. These (5-carba)isoalloxazines are novel examples for atropisomers with a C–N axis, the rotation of which is induced only by the redox reaction.