Concerning the Chiral Discrimination and Helix Inversion Barrier in Hypericinates and Hypericin Derivatives

Abstract

It was found that the hypericinate salts of (R)-1-phenylethylamine and (S)-1-(1-naphthyl)-ethylamine display a small chiroptical signal of the same sign only at high concentrations in an apolar solvent. No further indications of a chiral discrimination between the helical conformers of hypericinate could be found in these cases. However, upon esterification of the 3-hydroxyl group of hypericin with (1S)-camphanic chloride, the two diastereomers were found in an 1:1 ratio equilibrating rather fast at temperatures above 30°C with one diastereomer in excess. From the temperature dependence of the equilibrium positions (measured by means of CD and 1H NMR), a ΔG0 value of 5.8±0.5 kJ·mol−1 was derived. Accordingly, the chiral discrimination of the (M)-configured enantiomer of the helix by the (S)-configured auxiliary occurred at an intermediate level. From the temperature dependence of the equilibration kinetics an activation energy of Ea = 70±0.5 kJ·mol−1 was derived, which thus defines the upper limit of the helix inversion of hypericin and hypericinate. This value is by about 10 kJ·mol−1 lower than the recently estimated limit.