Fluorinated and phosphorated biomolecules: synthesis and application

Fluorinated biomolecules. Current developments in fluorinated molecules. Fluorination methods: nucleophilic or electrophilic mono-fluorination, introduction of difluoromethyl or trifluoromethyl groups. Contribution of fluorine atoms to the activity of these compounds. Examples of the synthesis of fluorinated compounds used as antitumoral agents, antiviral agents, antidepressants, anxiolytics, anti-inflammatories, etc.

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

A number of synthesis routes for compounds in each of the families covered will be discussed, highlighting unconventional activation methods where appropriate. Biomedical applications will be targeted, as well as other applications in agrochemistry, optoelectronics, nanomaterials, etc.

Hourly volumes* :

CM: 15 h (7.5h Fluorinated biomolecules and 7.5h Phosphorus biomolecules)

TD: 5 h

Expertise in the synthesis of fluorinated biomolecules

Phosphorus chemistry skills

L3 Organic chemistry

Final written exam, 2 hours:

• Authorized documents: no
• Internet allowed: no

Support(s) available on ENT (Moodle) : Course documents, TD documents, exam annals and reference publications.

Courses

Fluorinated biomolecules

1. Current developments in fluorinated molecules. 1,5 h

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

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

• Aminosulfurane and derivatives, N-fluorosulfinimide and derivatives

1. Introduction of trifluoromethyl or difluoromethyl groups. 1,5 h

• Ruppert-Prakash reagent and derivatives

1. Synthesis of fluorinated biomolecules (antitumor agents, antidepressants, etc.). 1,5 h

Phosphorus biomolecules

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

 - 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 to physico-chemical 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 medical applications 3 x 1.5 h

- Nucleotides, nucleotide analogues and prodrugs (anticancer, antiviral, diagnostic uses)

- Bisphosphonates (anti-osteoporosis, anticancer, theranostics)

- Phosphorus amino acids

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

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

TD (5 H) for both parts of the course: individual work, exercises to be prepared before and during the session.

Teaching team :

Christophe Mathé

Béatrice Roy

Jean-Pierre Uttaro

Administrative contact(s) :

Secretariat Master Chemistry

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