Fluorinated and Phosphorus-Containing Biomolecules: Synthesis and Applications

Fluorinated biomolecules. Current developments in fluorinated molecules. Fluorination methods: nucleophilic and electrophilic monofluorination; introduction of difluoromethyl or trifluoromethyl groups. The contribution of the fluorine atom(s) to the activity of these compounds. Examples of syntheses of fluorinated compounds used as antitumor and antiviral agents; antidepressants, anxiolytics, anti-inflammatory drugs, etc.

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

We will discuss several synthetic routes for compounds from each of the families covered, highlighting, where appropriate, unconventional activation methods. The focus will be on biomedical applications, as well as other applications in agrochemistry, optoelectronics, nanomaterials, and more.

Hourly volumes*:

CM: 3:00 p.m. (7.5 hours on fluorinated biomolecules and 7.5 hours on phosphorus-containing biomolecules)

TD: 5 hours

Expertise in the synthesis of fluorinated biomolecules

Expertise in phosphorus chemistry

L3 Organic Chemistry

2-hour final written exam:

• Authorized documents: No
• Internet access allowed: No

Resources available on the digital learning platform (Moodle): Course materials, tutorial materials, past exam papers, and reference publications.

Classes

Fluorinated biomolecules

1. Current Developments in Fluorinated Compounds. 1.5 hours

• Significance/Role of Fluorine Atoms in a Biomolecule

1. Methods of Nucleophilic and Electrophilic Monofluorination. 3 hours

• Aminosulfurane 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-containing molecules. 2 x 1.5 hours

 - Structure and Nomenclature of the 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 Medical Applications 3 x 1.5 hours

- Nucleotides, nucleotide analogs, and nucleotide prodrugs (anticancer agents, antivirals, diagnostic applications)

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

- Phosphorus-containing amino acids

- Phosphorylated steroid prodrugs (antibiotics, anti-inflammatory drugs, immunosuppressants)

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

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

Teaching Staff :

Christophe Mathé

Béatrice Roy

Jean-Pierre Uttaro

Administrative contact(s):

Master's in Chemistry Office

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