An unusual reaction of the natural compound benaphthamycin B: theoretical study of a model system

The surprising and complex transformation of benaphthamycin B to give quinone 2a is investigated theoretically with a model compound, 1,5-dihydroxy-4-methoxy-2,3-dimethylanthraquinone (3). The detailed study is performed using both DFT and perturbation theory under inclusion of solvent effects. Several individual steps (reduction and hydrolysis, water elimination, ether cleavage, and oxidation) of the proposed reaction cascade calculated at the PCM-MP2/6-31G(d)//B3LYP/6-31G(d) level of theory are presented and discussed. It is shown that the key step, the ether cleavage as an S(N)2 reaction leading to the anthrone 12a, possesses a smaller activation barrier compared to the alternative process yielding 12b. Therefore, the formation of the thermodynamically preferred model quinone 13a is also the kinetically favored pathway: The results of the calculated model reaction should also be valid for benaphthamycin B (1).