Dihydroflavins are facile reducing agents and potent nucleophiles. The dihydroflavin nucleophilic reactivity, as measured by the rate of covalent flavin adduct formation with tetrahydronaphthalene epoxides, is comparable to that of the thiolate anion (Y. T. Lee and J. F. Fisher (1993) J. Org. Chem. 58, 3712). In these reactions there appears subsequent to the nucleophilic cleavage of the epoxide by the dihydroflavin the product corresponding to formal hydride reduction product (at the benzylic carbon) of these epoxides. Thus the reaction of (+/-)-1a,2,3, 7b-tetrahydro-(1aalpha,2alpha,3beta,7balpha)-naphth[1,2-b]oxirene-2,3-diol (1), (+/-)-1a,2,3,7b-tetrahydro-(1aalpha,2beta,3alpha,7balpha)-naphth[1,2-b]oxirene-2,3-diol (2), and (+/-)-1a,2,3,7b-tetrahydro-(1aalpha,7balpha)-naphth[1,2-b]oxirene (3) in 9:1 (v/v) aqueous Tris buffer-dioxane, at both acidic and neutral pH, with FMNH(2) and 1,5-dihydrolumiflavin (LFH(2)) gave (following covalent flavin-epoxide adduct formation) the products having a methylene group at the benzylic position. The reduction product yield was proportional to the yield of the N(5) flavin-epoxide adduct intermediate, and the rate of the reaction was proportional to the dihydroflavin concentration. These observations are consistent with these reduction products resulting from bimolecular reaction between the dihydroflavin-epoxide adduct and a second molecule of dihydroflavin. Copyright 2000 Academic Press.