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

• Published in: Journal of molecular catalysis. B, Enzymatic Enzymatic, 2011, Vol.70 (1), p.32-40
• Main Authors: Simas, Alessandro Bolis Costa, Silva, Angelo Amaro Theodoro da, Cunha, Aline Gomes, Assumpção, Rafael Silva, Hoelz, Lucas Villas Bôas, Neves, Bianca Cruz, Galvão, Teca Calcagno, Almeida, Rodrigo Volcan, Albuquerque, Magaly Girão, Freire, Denise Maria Guimarães, de Alencastro, Ricardo Bicca
• Format: Article
• Language: English
• Subjects: active sites; Bioconversions. Hemisynthesis; Biological and medical sciences; Biotechnology; carboxylic ester hydrolases; catalytic activity; ethyl acetate; Fundamental and applied biological sciences. Psychology; Inositol; Kinetic resolution; Lipase; Methods. Procedures. Technologies; Molecular modeling; myo-inositol; Second tetrahedral intermediate; transesterification
• ISSN: 1381-1177; 1873-3158
• DOI: 10.1016/j.molcatb.2011.02.001

[Display omitted] ► Partially protected myo-inositol derivatives were assayed against different lipases. ► Diol (±)-1,2- O-isopropylidene-3,6-di- O-benzyl- myo-inositol ( rac-2) was resolved by CaL-B. ► Theoretical models of the tetrahedral intermediates from rac-2 and RmL or CaLB were developed. 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.