Studies related to anthracyclines. Part 1. Some Diels–Alder reactions of 4a,9a-epoxy-4a,9a-dihydroanthracene-1,4,9,10-tetrone

Abstract

The title compound (5b), prepared by the oxidation of anthracene-1,4,9,10-tetrone (4) with m-chloroperbenzoic acid, undergoes Dieels–Aldr reactions with cyclohexa-1,3-diene, cyclopentadiene, and 2-methylbuta-1,3-diene to give 5a,11a-epoxy-1,4-ethano-1,4,4a,5a,11a,12a-hexahydronaphthacene-5,6,11,12-tetrone (7a), 5a,11 a epoxy-1,4,4a,5a,11 a,12a-hexahydro-1,4-methanonaphthacene-5,6,11,12-tetrone (7b), and 5a,11a-epoxy-1,4,4a,5a,11a,12a-hexahydro-2-methylnaphthacene-5,6,11,12-tetrone (12), respectively. The foregoing cycloadducts, which are isolated as single stereoisomers, are assigned their stereo-structures on the assumption that the cycloaddition reactions occur by way of the least hindered endo-transition states. Reduction of the cycloadducts (7a), (7b), and (12) to give 1,4-ethano-1,4,4a,12a-tetrahydro-6,11-dihydroxynaphthacene-5,16-dione (10a), 1,4,4a,12a-tetrahydro-6,11-dihydroxy-1,4-methanonaphthacene-5,12-dione (10b), and 1,4,4a,12a-tetrahydro-6,11-dihydroxy-2-methylnaphthacene-5,12-dione (13), respectively, is achieved by using zinc in acetic acid or sodium dithionite in aqueous methanol. Lead(IV) acetate in acetic acid converts the dienes (10a), (10b), and (13) into 1,4-ethano-1,4,4a,12a-tetrahydronaphthacene-5,6,11,12-tetrone (9a), 1,4,4a,12a-tetrahydro-1,4-methanonaphthacene-5,6,11,12-tetrone (9b), and 1,4,4a,12a-tetrahydro-2-methylnaphthacene-5,6,11,12-tetrones (14), respectively. Aromatisation of the tetrones (9a), (9b), and (14) occurs in the presence of triethylamine to give the corresponding quinizarin derivatives (8a), (8b), and (15).