CHEMOENZYMATIC APPROACHES TO THE PREPARATION OF BIOLOGICALLY ACTIVE COMPOUNDS
type: CreativeWork
description: Biologically active compounds are usually polyfunctional molecules bearing one or more stereocenters. Enzyme catalyzed transformations are well suitable for their preparation since they act in a very mild and selective manner. The study of three selected biocatalyzed transformations has been the aim of my PhD researches. The first project, regards the development of an advantageous and mild method to selectively transform the 24-hydroxyl function of ascomycin, a 23-membered macrolactam, bearing two secondary alcoholic moieties bounded at position 24 and 32 of its macrocycle. This selective protection is required to transform ascomycin into pimecrolimus, its 32-epi chlorine analogue, an immunomodulator useful for the treatment of inflammatory skin diseases. The advantage offered by enzymes, showed to be not only their ability to regioselective discriminate between the two secondary hydroxyl groups, but also, their chemoselectivity, i.e. the capacity to leave intact the other functional groups present in the structure of ascomycin. Among enzymes to screen for the desired transformation we selected lipases, taking into account their well know regioselectivity in the acylation of secondary alcohols and their efficiency to transform lipofilic compounds. The second topic regards the clopidogrel, a thienopyridine compound that inhibits platelet aggregation by selectively binding to adenylate cyclase-coupled ADP receptors. It is indicated for the reduction of atherosclerotic events. Its structure contains a stereocenter: since only the S(+) isomer is biologically active, the compound must be prepared in the enantiomerically pure form. Although it is known and used by several years, usually this target is achieved by means of time consuming and expensive fractional crystallization of the unnatural aminoacid easily recognizable in its structure, 2-chloro-phenylglycine. The aim of my work was to find an enzymatic approach to achieve the suitable resolution with a low cost and …
abstract: Biologically active compounds are usually polyfunctional molecules bearing one or more stereocenters. Enzyme catalyzed transformations are well suitable for their preparation since they act in a very mild and selective manner. The study of three selected biocatalyzed transformations has been the aim of my PhD researches. The first project, regards the development of an advantageous and mild method to selectively transform the 24-hydroxyl function of ascomycin, a 23-membered macrolactam, bearing two secondary alcoholic moieties bounded at position 24 and 32 of its macrocycle. This selective protection is required to transform ascomycin into pimecrolimus, its 32-epi chlorine analogue, an immunomodulator useful for the treatment of inflammatory skin diseases. The advantage offered by enzymes, showed to be not only their ability to regioselective discriminate between the two secondary hydroxyl groups, but also, their chemoselectivity, i.e. the capacity to leave intact the other functional groups present in the structure of ascomycin. Among enzymes to screen for the desired transformation we selected lipases, taking into account their well know regioselectivity in the acylation of secondary alcohols and their efficiency to transform lipofilic compounds. The second topic regards the clopidogrel, a thienopyridine compound that inhibits platelet aggregation by selectively binding to adenylate cyclase-coupled ADP receptors. It is indicated for the reduction of atherosclerotic events. Its structure contains a stereocenter: since only the S(+) isomer is biologically active, the compound must be prepared in the enantiomerically pure form. Although it is known and used by several years, usually this target is achieved by means of time consuming and expensive fractional crystallization of the unnatural aminoacid easily recognizable in its structure, 2-chloro-phenylglycine. The aim of my work was to find an enzymatic approach to achieve the suitable resolution with a low cost and …
author: M. DE MIERI
language: eng
keywords: Biocatalysis, Lipases, Proteases, Pimecrolimus, Clopidogrel, Amidotransferase inhibitors, Settore BIO/10 - Biochimica
date published: 2010-12-09
date modified: 2026-07-27T20:19:17Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2434/148883

PropertyValue
property ID: DOI
value: 10.13130/de-mieri-maria_phd2010-12-09