Ricerc@Sapienza

One of the most important challenges in synthetic chemistry is the rapid and high-yield synthesis of complex molecules from simple building blocks. Many of these syntheses require the highly reactive aldehyde functional group, which can be used for (asymmetric) aldol, and Mannichtype reactions as well as Grignard additions, Wittig reactions, oxidations and reductions. Aldehydes are not only essential building blocks for the synthesis of pharmaceuticals, they also play an important role in food and flavor industry. Aldehydes are mainly synthesized by chemical oxidation of primary alcohols, by ozonolysis or the reduction of activated carboxylic acid derivatives. However, these systems are not environmentally friendly. Over the last decade, novel methodologies were developed, especially in the field of biocatalysis. Indeed, aldehydes can be synthesized in a completely green way by enzymatic means. In nature, several enzymes produce aldehydes: alcohol oxidases and alcohol dehydrogenases that convert alcohols to aldehydes; carboxylic acid reductases and aldehyde oxidoreductases that reduce carboxylates to aldehydes; amine oxidases that catalyze the oxidative deamination of primary amines. At present, none of these enzymes have been used for semi-preparative or preparative aldehyde synthesis.
Amine oxidases, the copper containing enzymes extracted from Leguminosae seedlings, appeared particularly attractive because they show a rather broad substrate specificity and a remarkable stability profile. On this basis, we will develop an enzymatic green method for gram-scale synthesis of aldehydes starting from a variety of beta-substituted ethylamines using Lathyrus cicera (chick pea) amine oxidase (LCAO). To this purpose, we will set up a new purification method involving cross flow ultrafiltration and a series of immobilization strategies to allow for enzyme recovery and reutilization. Evaluation of LCAO activity will be done also in Natural Deep Eutectic Solvents (NADES).