Synergistic effects of ionic liquid-solvent systems on geniposide cinnamoylation catalyzed by whole-cell biocatalysts

A highly efficient and regioselective method for the synthesis of pharmacologically active geniposide 6´-cinnamate is reported herein for the first time, employing Aspergillus oryzae whole cells as biocatalysts in an acetonitrile-ionic liquid co-solvent system. The catalytic performance was markedly enhanced in the presence of ionic liquids compared to the pure acetonitrile system, with catalytic efficiency influenced by the nature of the anion species (e.g., BF₄⁻, PF₆⁻, Tf₂N⁻) and the structure of the cation (including [BMIM]⁺, [OMIM]⁺, [HMIM]⁺). In the optimized acetonitrile-[OMIM][PF₆] (1%, v/v) system, 99% substrate conversion was achieved within 24 h, with an initial reaction rate of 10.88 mmol·L⁻¹·h⁻¹, approximately twice that observed in pure acetonitrile (5.1 mmol·L⁻¹·h⁻¹). Furthermore, the catalyst exhibited excellent 6’-regioselectivity (> 99%) and remarkable operational stability, retaining 42% of its initial activity after six consecutive batches. In conclusion, incorporating ionic liquids as co-solvent effectively promotes catalytic modification of geniposide in whole cells, offering a novel and economically viable strategy for efficiently synthesizing its derivatives.