Fluorinated and phosphorous biomolecules: synthesis and applications

Fluorinated biomolecules. Current developments in fluorinated molecules. Fluorination methods: nucleophilic and electrophilic monofluorination, introduction of difluoromethyl or trifluoromethyl groups. Contribution of fluorine atoms to the activity of these compounds. Examples of syntheses of fluorinated compounds used as antitumor agents, antivirals, antidepressants, anxiolytics, anti-inflammatories, etc.

Phosphorus-containing biomolecules. Structure, nomenclature, reactivity, structural analysis, and applications.

Several methods for synthesizing compounds from each of the families covered will be discussed, highlighting unconventional activation methods where applicable. Biomedical applications will be targeted, as well as other applications in agrochemistry, optoelectronics, nanomaterials, etc.

Hourly volumes:

CM: 15 hours (7.5 hours fluorinated biomolecules and 7.5 hours phosphorous biomolecules)

Tutorial: 5 hours

Skills in the synthesis of fluorinated biomolecules

Skills in phosphorus chemistry

L3 Organic Chemistry

2-hour final written exam:

• Authorized documents: no
• Internet access: no

Support materials available on the digital workspace (Moodle): Course documents, tutorial documents, past exam papers, and reference publications.

Class

Fluorinated biomolecules

1. Current developments in fluorinated molecules. 1.5 hours

• Interest/Contribution of fluorine atom(s) to a biomolecule

1. Nucleophilic and electrophilic mono-fluorination methods. 3 hours

• Aminosulfuran and derivatives, N-fluorosulfinimide and derivatives

1. Introduction of trifluoromethyl or difluoromethyl groups. 1.5 hours

• Ruppert-Prakash reagent and derivatives

1. Synthesis of fluorinated biomolecules (antitumor agents, antidepressants, etc.). 1.5 hours

Phosphorus-containing biomolecules

1. The element phosphorus and phosphorus molecules. 2 x 1.5 hours

 - Structure and nomenclature of functional groups of P(III) and P(V) derivatives

 - Structure and biological functions of phosphorus-containing biomolecules: nucleotides, nucleic acids, phospholipids, etc.

- Phosphorus NMR: applications in physicochemical characterization and reaction monitoring

- Major reactions involving phosphines (Appel, Mitsunobu, Staudinger, aza-Wittig), phosphites (Michaelis-Arbuzov), phosphonium ylides (Wittig), phosphine oxides (Wittig-Horner), phosphonates (Horner-Wadsworth-Emmons), and H-phosphonates (Michaelis-Becker, Atherton–Todd)

1. 2. Organophosphorus compounds: synthesis and applications in the medical field 3 x 1.5 hours

- Nucleotides, analogues, and nucleotide prodrugs (anti-cancer, antiviral, use in diagnostics)

- Bisphosphonates (anti-osteoporotic, anti-cancer, theranostic agents)

- Phosphorus amino acids

- Phosphate prodrugs of steroids (antibiotics, anti-inflammatories, immunosuppressants)

- Oxazaphosphorines and phosphorotriamidates (DNA alkylating agents, anticancer drugs)

Tutorial (5 hours) for both parts of the course: Individual work, exercises to be prepared before and during the session.

Teaching staff :

Christophe Mathé

Beatrice Roy

Jean-Pierre Uttaro

Administrative contact(s):

Master's Program in Chemistry Secretariat

https://master-chimie.edu.umontpellier.fr/