Methylation of hallerin: conformational aspects from X-ray analysis and MO calculations

Abstract

The stereochemistry at the ketal centre of methylhallerin (6) has been established by X-ray analysis. The stereochemical outcome of the methylation of hallerin and of pairs of related anomeric sesquiterpene lactols has been studied by means of geometrical and theoretical calculations (MNDO method). Model lactols and methyl lactols were chosen with conformational features simulating the effects of the presence of the ten-membered ring in as found in (6) the solid state. The results showed that neither thermodynamic nor steric effects alone can explain the fact that exclusively one methyl derivative is obtained upon alkylation of the pairs of anomeric lactols with CH₃I–Ag₂O. However, the anomeric lactols investigated show a difference in accessibility towards methylation, which, although not relevant in solution, might play an important role when the molecule is adsorbed on the surface of Ag₂O, where the alkylation reaction is expected to take place.