Author(s): Queda, Fausto Daniel dos Santos
Date: 2019
Persistent ID: http://hdl.handle.net/10362/90888
Origin: Repositório Institucional da UNL
Subject(s): Peptidoglycan; Sustainable Chemistry; Chitin; Chitosan; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química
Peptidoglycan (PGN) is a major component of the bacteria cell wall that surrounds and protect bacteria from the surrounding environment. The composition of PGN is often linked with the outcome of bacterial infections and its synthesis is the target of the different classes of antibiotics frequently used in the treatment of these bacterial infections. The scientific community has been requesting to availability of increasing amounts of pure, well defined, PGN fragments in order to be able to move forward with the biological studies in a reliable way. The extraction processes used to purify PGN from bacteria rely on the use of harsh conditions that can be harmful to the user and also the environment. Thus, through the last thirty years, different groups have been dedicating time and resources to establish new synthetic routes to produce PGN fragments of different composition. These routes rely on the use of fully functionalized glucosamine building blocks, through a protecting group orthogonal synthesis, followed by glycosylation and peptide coupling reactions. The challenge, fully framed in a sustainable chemistry doctoral program, was to develop new synthetic routes towards PGN fragments using more sustainable processes. In this thesis it is reported the synthesis of PGN fragments using as starting material the polymers of chitin and chitosan, which are present in significant amount in food industry wastes. In the first approach, an acetolysis reaction of chitin was used to give a peracetylated disaccharide, in a gram scale amount, which, through protecting group orthogonal synthesis, can give an advanced PGN intermediate in a five synthetic steps. As this intermediate possesses all the functional groups in the correct position as the PGN fragments, it may be considered a high value synthetic intermediate. On the second approach, the polymer of chitosan was used as starting material in a chemoenzymatic synthesis. Through orthogonal protecting group strategy, it was possible modify a high weight chitosan molecules in order to produce a PGN surrogate. Using commercially available PGN hydrolases, we were able to hydrolyze this surrogate in order to identify the oligosaccharides that are present in the PGN sugar backbone.
