Chemo-Enzymatic Cascade for the Generation of Fragrance Aldehydes

In this study, we present the synthesis of chiral fragrance aldehydes, which was tackled by a combination of chemo-catalysis and a multi-enzymatic in vivo cascade reaction and the development of a highly versatile high-throughput assay for the enzymatic reduction of carboxylic acids. We investigated a biocompatible metal-catalyzed synthesis for the preparation of alpha or beta substituted cinnamic acid derivatives which were fed directly into the biocatalytic system. Subsequently, the target molecules were synthesized by an enzymatic cascade consisting of a carboxylate reduction, followed by the selective C-C double bond reduction catalyzed by appropriate enoate reductases. We investigated a biocompatible oxidative Heck protocol and combined it with cells expressing a carboxylic acid reductase from Neurospora crassa (NcCAR) and an ene reductase from Saccharomyces pastorianus for the production fragrance aldehydes.

Automated summary

This study focused on the synthesis of chiral fragrance aldehydes using a combination of chemo-catalysis and multi-enzymatic in vivo cascade reaction, as well as the development of a highly versatile high-throughput assay for enzymatic reduction of carboxylic acids. A biocompatible metal-catalyzed synthesis was used to prepare alpha or beta substituted cinnamic acid derivatives, which were then fed into a biocatalytic system for the synthesis of target molecules through enzymatic cascade reactions. The production of fragrance aldehydes was achieved by combining a biocompatible oxidative Heck protocol with specific enzymes expressed in cells.