Fluorinated and phosphorated biomolecules: synthesis and application

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

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

Some synthetic routes of compounds of each of the treated families will be discussed, highlighting, if necessary, non-conventional activation methods. Biomedical applications will be targeted, as well as other applications in agrochemistry, optoelectronics, nanomaterials, ...

Hourly volumes* :

CM : 15 h (7,5h Fluorinated biomolecules and 7,5h Phosphorated biomolecules)

TD : 5 h

Expertise in the synthesis of fluorinated biomolecules

Phosphorus chemistry skills

L3 Organic Chemistry

Final written exam of 2 hours:

• Authorized documents: no
• Internet allowed : no

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

Course

Fluorinated biomolecules

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

• Interest/ Contribution of the fluorine atom(s) on 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 drugs, antidepressants, ...). 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 physicochemical characterization and reaction monitoring

- The 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 h

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

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

- Phosphorus-containing 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 prepare 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/