Catalytic and molecular properties of rabbit liver carboxylesterase acting on 1,8-cineole derivatives.

Rabbit liver carboxylesterase (rCE) was evaluated as the catalyst for the enantioselective hydrolysis of (+/-)-3-endo-acetyloxy-1 ,8-cineole [(+/-)-4], which yields (1S,3S,4R)-(+)-3-acetyloxy-1,8-cineole [(+)-4] and (1R,3R,4S)-(-)-3-hydroxy-1,8-cineole [(-)-3]. Enantioselective asymmetrization of meso-3,5-diacetoxy-1,8-cineol (5) gives (1S,3S,4R,5R)-(-)-3-acetyloxy-5-hydroxy-1,8-cineole (6), with high enantioselectivity. rCE has been chosen to perform both experiments and molecular modeling simulations. Docking simulations combined with molecular dynamics calculations were used to study rCE-catalyzed enantioselective hydrolysis of cineol derivatives. Both compounds were found to bind with their acetyl groups stabilized by hydrogen bond interactions between their oxygen atoms and Ser221.

Vibrational circular dichroism of Africanane and lippifoliane sesquiterpenes from Lippia integrifolia.

The agreement between theoretical and experimental vibrational circular dichroism curves of (4R,9R,10R)-(+)-african-1(5)-ene-2,6-dione (1) and (4R,9S,10R)-lippifoli-1(6)-en-5-one (2), isolated from the widely used plant Lippia integrifolia, allowed the determination of the conformation and absolute configuration of 1 and confirmed both structural features for 2. Molecular modeling of 1 and 2 was carried out by means of a systematic and a Monte Carlo search protocol followed by geometry optimization employing density functional theory calculations with the B3LYP/6-31G(d), B3LYP/DGDZVP, and/or B3PW91/DGDZVP2 functionals/basis sets. Validation of the minimum energy conformations for both tricyclic substances was achieved by comparison of the experimental and theoretical vicinal (1)H-(1)H NMR coupling constants obtained by DFT-GIAO calculations.