Rigidone or ent-perezone?

Abstract

Introduction The 13C-NMR data described for perezone (1), a 3-hydroxy p-quinone stated as the first natural product isolated as crystals in the New World, and rigidone (2), a 4-hydroxy o-quinone isolated from a coral species, are essentially the same. Some years ago, we described, using theoretical calculations, that a 4-hydroxy-1,2-quinone is more than 11 kcal/mol less stable than a 3-hydroxy-1,4-quinone making coexistence in nature of this type of quinones. In the present study, we approach the situation by comparing of the experimental 13C-NMR data for 1 and those described for 2 with the calculated using computational methods. Additional evidence was obtained from a X-ray diffraction analysis for the reaction product of perezone with o-phenylendiamine. Methods The 13C-NMR data for the quinoid rings were calculated using the GIAO and CSGT methods, density functional theory (DFT) and the functional/basis set pairs B3LYP/6-31 g(d,p) and MPW1PW91/6-31 g(d,p); and TPSSTPSS/cc-PVTZ and PBE1PBE/aug-cc-PVDZ. Perezone reaction with o-phenylenediamine was achieved using a described method in MeOH at room temperature. X-Ray diffraction analysis of phenazine from perezone reaction was done using Mo Kα radiation. The data were used to calculate the Flack parameter. Results After conformational analysis, complete optimization of the geometry of the conformers found and, calculation of the 13C-NMR chemical shifts for the quinone ring of 1 and 2, in all cases a better agreement was observed between the experimental data for 1 versus 2. Perezone reaction with o-phenylenediamine afforded the corresponding phenazine in its amine-keto tautomeric form as evidenced from a X-ray diffraction study. Conclusion The better agreement observed between the experimental and calculated data for 1 versus 2, along with the free energy difference of more than 11 kcal/mol in favor of the 3-hydroxy p-quinone versus 4-hydroxy o-quinone, previously established for us, allow to say that the structure described for rigidone corresponds to ent -perezone.