High- and Low-Potential Flavin Mimics. 3. 3,7,10-Trimethyl-(1H,3H,5H,7H,9H,10H)-pyrimidopteridine-2,4,6,8-tetrone-Mediated Reduction of Carbon-Carbon Double Bond α-β to an Acyl Function

Article abstract of DOI:10.1021/ja00267a040

The reduction of the carbon-carbon double bond of maleimide (MI), N-methylmaleimide (NMM), ethyl fumarate, diethyl fumarate, diethyl maleate, fumaric acid, and maleic acid was investigated by employing the low redox potential flavin mimic 3,7,10-trimethyl-(1H,3H,5H,7H,9H,10H)-pyrimido<5,4-g>pteridine-2,4,6,8-tetrone (PPTH2) as the reductant.The reaction of these substrates with PPTH2 to produce PPT_ox and the corresponding succinimide or succinate consists of three processes.The first process occurs on mixing and pertains to the formation of a mixture of N(1)- and C(4a)-substrate adducts of PPTH2.The other two processes, which are kinetically distinguishable, pertain to the breakdown of each of these adducts to PPT_ox and the reduced substrate.Breakdown of the C(4a)-adduct is catalyzed by hydroxide and is independent of substrate concentration.Hydroxide catalysis is proposed to represent a concerted process whereby the hydroxide abstracts the N(5)-proton while the anionic reduced substrate is departing (Bronsted β approaching 1.0).Breakdown of the N(1)-adduct to the observed products is substrate-dependent pertaining to the rate-determining formation of the N(9),C(4a)-diadduct.In a fast step, base-catalyzed elimination from the C(4a)-position of the latter provides the reduced substrate anion and the N(9)-monosubstrate adduct of PPT_ox.Rapid dissociation of the N(9)-adduct then provides PPT_ox.It is concluded that the reduction of a carbon-carbon double bond to an acyl function by the low-potential flavin mimic proceeds via C(4a)-adducts.This conclusion and the principle of microreversibility infers that enzyme-bound flavins of high potential, as in dehydrogenating flavoenzymes, may oxidize succinates to fumarates via C(4a)-adducts.