Doctoral themes 2023

Sustainable synthesis of novel potentially bioactive nucleotide analogs from biomass resources 

Supervisors

Ana Cristina Silva Fernandes, anacristinafernandes@tecnico.ulisboa.pt

Nuno Manuel R. M. Xavier, nmxavier@ciencias.ulisboa.pt

Registration Institution

Faculdade de Ciências, Universidade de Lisboa

Project description

Synthetic nucleosides, nucleotides and analogs are relevant compounds in organic and medicinal chemistry, owing to their propensity to exhibit a variety of bioactivities, and their interest in drug discovery is well demonstrated by the number of compounds of these groups that became drugs for cancer and for viral diseases. There are however some drawbacks associated with their use, namely low bioavailability and chemotherapeutic resistance. The search for new nucleos(t)ide-like structures as well as the development of practical, efficient and scalable methods for their synthesis remains of interest.  

Herein the sustainable synthesis of innovative types of nucleotide analogs comprising α- and β-aminophosphonate groups, which are relevant phosphate-analogous moieties in medicinal chemistry, particularly due to their structural analogy to the α- and β-amino acid systems, is intended. As starting materials, readily available biomass-derived carbohydrates (e.g. xylose, xylan) will be used and converted into suitable synthons by environmentally-friendly methodologies for further installation of an aminophosphonate system. The core nucleosidic structures will be based on those of previously reported anticancer nucleoside analogs from our team. The therapeutic potential of the new molecules, namely their in-vitro anticancer activities and their abilities to inhibit therapeutically relevant enzymes, will be evaluated in collaboration with foreign academic partners and the student will participate in these studies at the foreign institution during one month each year of his PhD work.  

This proposal lies within the context of 2 CQE thematic lines (SUSChem, MEDLife), aiming at developing new molecules of potential therapeutic interest by using sustainable synthetic methods.  

Keywords

Nucleos(t)ides

Aminophosphonates

Carbohydrates

Bioactive molecules

Biomass