Kinetic resolution of (±)-1,2-O-isopropylidene-3,6-di-O-benzyl-myo-inositol by lipases: An experimental and theoretical study on the reaction of a key precursor of chiral inositols

The study on kinetic resolution of two myo-inositol derivatives by lipases is reported. Treatment of the triether derivative, (±)-1,2-O-isopropylidene-3,5,6-tri-O-benzyl-myo-inositol, with acylating agents in the presence of different lipases did not afford any detectable amount of acylated products. We speculate that the severe steric hindrance posed by this substrate precluded interaction with the enzymes’ catalytic site. Conversely, diol (±)-1,2-O-isopropylidene-3,6-di-O-benzyl-myo-inositol, a key precursor of chiral myo-inositol derivatives, bearing one less benzyl protecting group, underwent a successful transesterification in EtOAc, catalyzed by CaL-B (Novozym 435). Thus, monoacetate l-(−)-1,2-O-isopropylidene-3,6-di-O-benzyl-5-O-acetyl-myo-inositol was regioselectively formed in >99% ee. Additionally, we developed theoretical models of the second tetrahedral intermediate (TI) complex of this reaction to explain the success of the CaL-B and the inactivity of RmL against the same substrate.