Fluorination in Medicinal Chemistry

BYRonald Mensah

Introduction Fluorination methods Fluorination in Medical chemistry Conclusion Writing Component References Questions

Outline

Introduction

What is fluorine? Location on the

periodic table Electronegativity Ionization energy Natural abundance

http://www.ebi.ac.uk/chebi/searchId.do?chebiId=24065. accessed on 10/2/2014

Electrophilic Fluorinations

Nucleophilic Fluorinations

Procedures

What occurs in electrophilic fluorination reaction?

Cationic fluorine atom N-F and 0-F reagent Removal of electron density

Electrophilic Fluorination

Electrophilic addition

Direct displacement with fluoride

Protic vs aprotic solvent tetrabutylammoniumfluoride(TBAF)

Other Regents HF (diethylamino)-sulfur trifluoride (DAST)

Use of transition metals

Nucleophilic fluorination.

http://www.sigmaaldrich.com/catalog/product/aldrich/216143?lang=en&region=US

Nucleophilic Fluorination mechanism

H---F

Orthogonal reactivity of Hydrogen and

Fluoride H+ vs F+

H- vs F-

enzyme activity design 5-fluorouracil (5-FU) pyridoxal phosphate (PLP)-dependent enzyme-

catalyzed reactions

Medicinal Chemistry

5-fluorouracil (5-FU)

DFMO (Eflornithine)

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Conclusion

References

Banks, Alton. "Fluorine." Journal of Chemical Education 67.5 (1990): 373. ACS. Web

Kirk, Kenneth L. "Fluorination in Medicinal Chemistry: Methods, Strategies, and Recent Developments." Organic Process Research & Development 12.2 (2008): 305-21.

Lal, G. Sankar, Guido P. Pez, and Robert G. Syvret. "Electrophilic NF Fluorinating Agents." Chemical Reviews 96.5 (1996): 1737-756. Print.

Questions?