Conformation and tautomerism of hypocrellins. Revised structure of shiraiachrome A

Abstract

Hypocrellins, natural perylenequinones from the fungi Hypocrella bambusae and Shiraia bambusicola, are being intensively studied for their photodynamic activity. As a recent paper reported the existence of a slow tautomeric equilibrium for hypocrellin A, the behaviour in solution of hypocrellin and hypocrellin A was reinvestigated by NMR. 1D and 2D ROESY spectra at different temperatures and in different solvents have been measured and quantitative NOE experiments have been performed to obtain the cross-relaxation rates and then the interproton distances, to be used for MM and MD calculations. This allowed us to confirm that tautomerism in these compounds is a fast process on the NMR time scale, and to establish the relative population of the two principal tautomers and the preferred conformation of hypocrellin, hypocrellin A and of their atropisomers. The atropisomeric interconversion process is fast enough to be studied by NMR; the rate constants, obtained by ROESY-exchange experiments, gave the activation parameters. The helix inversion also induces the inversion of the seven-membered ring, which adopts a twist–boat conformation in both atropisomers. The values of the dihedral angle C(1)–C(12b)–C(12a)–C(12), which shows the distortion of the perylenequinone system, have been obtained from energy minimisation of the structures derived from NOE data. They are in the range 25–29° for all stereoisomers. The structure of shiraiachrome A, another member of the series, has been revised to M(R),14S,16S. The conformation and the tautomeric equilibrium of this compound have been similarly determined.