BIOCATALYTIC STRATEGIES FOR SELECTIVE ORGANIC SYNTHESIS

• Main Author: I. Bassanini
• Other Authors: tutor: D. Passarella, co-tutor: S. Riva, coordinatore: E. Licandro, PASSARELLA, DANIELE, LICANDRO, EMANUELA
• Format: Doctoral or Postdoctoral Thesis
• Language: English
• Published: Università degli Studi di Milano 2018
• Subjects: Biocatalisi; sintesi organica; enzimi; natural products; Settore CHIM/06 - Chimica Organica; Antarc*; Antarctica
• Online Access: http://hdl.handle.net/2434/541374; https://doi.org/10.13130/bassanini-ivan_phd2018-01-26

Proteins are macromolecules constituted by a network of chiral (L)-alpha-amino acids linked by amide bonds that, thanks to their extensive chirality and 3D-folding, can catalyze highly selective transformations. Thus, enzymes can discriminate between two enantiomers (ndr kinetic resolution), interact with a pro-chiral group leading to the stereoselective formation of a new stereocenter (ndr asymmetric synthesis) or can guide the chemical bonds formation or breaking in a specific direction as well as toward a specific functional group (ndr regio- and chemo-selective processes). In this research work, different enzymatic activities have been exploited to promote selective transformations to assess synthetic problems in organic chemistry. The regioselective lipase-mediated trans-acylation reactions, discussed in a review article published by our research group in 2015, have been exploited to selectivity produce aloin conjugates) to be tested for their ability as self-assembly inducers. The outstanding regioselectivity of an immobilized Candida antarctica (Novozym435) and lipase PS allowed to produce key synthons of the target compounds via the selective acylation of the aglycone primary hydroxyl group. A subclass of novel thermostable aminotransferases (B3, It6 and Is3; TM up to 80 °C) discovered from hot-spring metagenomes, was investigated for their potential synthetic exploitation to prepare enantiomerically enriched amines. In this work, more than 10 amino donors and acceptors were screened as substrates to produce (S)-primary amines by direct asymmetric synthesis from the correspondent pro-chiral ketones. A sustainable, convenient, scalable, one-pot, two-enzyme method for the glucosylation of arylalkyl alcohols was developed. The reaction scheme was based on a transrutinosylation catalyzed by a rutinosidase from A. niger using the cheap commercially available natural flavonoid rutin as glycosyl donor, followed by selective ‘trimming’ of the rutinoside unit catalyzed by a rhamnosidase from A. terreus. The ...