Combinatorial Synthesis of Chiral Esters from Fruit Aroma in Continuous-Flow Reactors by Chemical and Enzymatic Catalysis

Short-chain chiral esters are important constituents in natural fruit flavors, as well as in food and pharmaceutical industries. Different chemical and bio-catalytic routes are used for their synthesis, but the use of simultaneous techniques has not been much explored, as combinatorial synthesis and bio-catalysis in continuous-flow systems. Here, the objective was to synthesize chiral esters typically found in fruit flavors, to obtain chemical libraries with high conversion and enantiomeric excess, using combinations of these three techniques. Combinatorial synthesis in continuous-flow coil-type reactors with fix bed was used in the esterification of the secondary alcohols 2-butanol (1a), 2-pentanol (1b), 3-hexanol (1c), 2-heptanol (1d) and 2-octanol (1e) with acetic (2) and propanoic (3) acids. A surface-response method was applied to optimize the reaction conditions. Conversions were above 88% after 60 min for the reaction with chemical catalysts in continuous-flow reactors compared to 85%, but after 120 min, when conventional batch processes were used. By applying a biocatalyst, a chemical library of R acetates was prepared, with conversions over 48% after 48 h for batch and 40% after only 70 min for continuous flow reactions. It was observed that both enzymatic and homogeneous chemical catalysis showed to be viable for the chiral esters.

Keywords:
fruity esters; enantioselectivity; chiral GC; flow chemistry; rotational central composite design