Novel biocatalyzed flow synthesis of nature-inspired Phenolic Carbonate and Carbamate derivatives as antiradical and antimicrobial agents

• Main Author: Sara Vicinanza
• Other Authors: S. Vicinanza
• Format: Conference Object
• Language: English
• Published: 2022
• Subjects: Settore CHIM/08 - Chimica Farmaceutica; Antarc*; Antarctica
• Online Access: https://hdl.handle.net/2434/1021510; http://www.sintesi.unimi.it/index.html

Green Chemistry allows the control of environmental hazards and pollution, reducing chemical waste and dangerous effects on workers’ health [1]. Recently, the use of continuous biocatalysis has become widespread in API synthesis, stimulating the application of immobilized enzymes in packed bed reactors, allowing the overcoming of some practical problems connected to batch procedures, such as product inhibition, low productivity, scalability, biocatalyst stability and product and/or intermediate degradation [2]. During my Thesis, I worked on the development of two novel continuous synthetic protocols exploiting the combination of the flow chemistry and biocatalysis for the obtainment of carbonate and carbamate derivatives of natural phenolic compounds, characterized by increased lipophilicity compared to the parent compounds (Figure 1). As natural phenolic compounds, I selected tyrosol and hydroxytyrosol, mainly present in olive oil, due to their broad range of biological activities and their potential health benefits in particular as natural antioxidants [3]. It is noteworthy that phenols and catechols can transfer the hydrogen from the phenolic hydroxyl group to different reactive oxygen species, reducing the oxidative stress in cells (Figure 2) and, as reported in literature, several alkyl-carbonate derivatives of hydroxytyrosol possess an increased activity compared to the parent compound, heightening the molecule lipophilicity and dimensions [4]. In addition, different natural antimicrobial agents can be plant origin, such as tyrosol, whose mechanism is related to the ATP synthase inhibition, and hydroxytyrosol, whose activity depends on the bacterial strains [5]. During my Thesis, first, I synthesized tyrosol and hydroxytyrosol carbonate derivatives (Figure 1, compounds 1-3) exploiting an immobilized lipase from Candida antarctica (CaLB) as biocatalyst in an unconventional organic medium as dimethyl carbonate (DMC). The reaction was studied in batch and then moved to flow. The switch from a batch ...