New sustainable biocatalytic approach for producing lipophilic (hydroxy)cinnamic esters based on deep eutectic mixtures

Abstract

Hydroxycinnamic acids (HCAs) are naturally occurring compounds highly valued for their bioactive properties that contribute to health benefits. The biocatalytic acylation of HCAs with fatty alcohols (FAs) is a suitable strategy to facilitate their incorporation to hydrophobic matrices (e.g. cosmetic creams), although this modification is hampered by the immiscibility between both substrates. This work demonstrates the excellent suitability of deep eutectic mixtures to afford the clean biocatalytic synthesis of natural hydrophobic esters derived from trans-cinnamic, para-coumaric, caffeic and hydrocaffeic acids, and different aliphatic (1-hexanol, 1-dodecanol, cis 9-octadecenol) and terpenic (geraniol, β-citronellol) alcohols in solvent-free conditions. Through the technology of eutectic mixtures, an easy co-solubilization of both substrates was achieved at 1:8 HCA:FA molar ratio without addition of co-adjuvants/solvents. These homogeneous mixtures were shown to be excellent reaction media for Novozym 435-catalyzed esterification processes (e.g. 8–96 h at 70 °C), leading to product yield near to 100% for most cases (up to 1262 µmol ester / g N435 for the case of hydrocaffeic:cis 9-octadecen-1-ol mixture), preserving their antioxidant activity according to the DPPH assay. By this approach, the sustainability of the synthetic processes was enhanced leading to a higher atom efficiency and lower waste production, as measured by different Green Metrics parameters.