Pouteria sapota hydroxynitrile lyase catalyzed synthesis of optically active cyanohydrins from ortho-substituted benzaldehydes

Abstract

Chiral cyanohydrins are important building blocks in the preparation of pharmaceuticals and agrochemicals. The synthesis of optically active o-substituted mandelonitriles was carried out in a biphasic system, using the defatted meal of Pouteria sapota seeds as (R)-hydroxynitrile lyase (PsHNL) source to biocatalyze the enantioselective addition of HCN to the sterically hindered o-chloro, o-bromo, o-fluoro, o-nitro, o-methyl, and 2,4-dichlobenzaldehydes, that are poor substrates for other HNLs. The enantiomeric excess (ee) of the cyanohydrins obtained was from 98 to 100 %, except in the case of o-nitromandelonitrile (82 % ee), the conversion was from 56 % to 100 %, at the optimum conditions of 2 mL diisopropyl ether (i-pr2O), 37.5 %, of aqueous phase and ratio 60 mg/0.5 mmol of PsHNL meal/aldehyde. The relationship between molecular descriptors and bioconversion of the o-substituted benzaldehydes was analyzed using Person´s correlation (r ≤ 0.8) and path analysis, the molecular descriptors that had a highest influence over the conversion were Total size indexes (T) weighted by atomic van der Waals volume (Tv), atomic polarizability (Tp), atomic Sanderson electronegativity (Te) and unweighted (Tu). The P. sapota seed is an inexpensive source of HNL, that was able to biocatalyze the conversion of sterically hindered benzaldehydes to the corresponding enantiopure cyanohydrins.