FATE-MP: Fluorine as a unique tool to engineer molecular properties

• Forschungsstelle: EU FRP
• Projektnummer: 97.0083
• Projekttitel Englisch: FATE-MP: Fluorine as a unique tool to engineer molecular properties

Schlüsselwörter (Englisch)

Organofluorine chemistry; new synthetic methods; bioactive compounds

Alternative Projektnummern (Englisch)

EU project number: FMRXCT970120

Forschungsprogramme (Englisch)

EU-programme: 4. Frame Research Programme - 10.1 Stimulation of training and mobility

Kurzbeschreibung (Englisch)

See abstract

Partner und Internationale Organisationen (Englisch)

Coordinator: Universität Bochum.(D)

Abstract (Englisch)

The work accomplished was driven by two major impulses. On one hand, we wanted to gain deeper insight in the behavior of fluorine as substituent in order to make predictable how it affects the physical, chemical and biological properties of given organic compounds. At the same time, we endeavored to open an access to novel building blocks displaying structural patterns which look enticing for life science-oriented research.
We were fortunate enough to attain all principal objectives. A few achievements are highlighted below :
· In collaboration with industry we have collected pKa and lgP values of whole families of fluorinated model compounds. The long-term goal is to compile huge numbers of such physiologically significant characteristics in order to parametrize fluorine effects.
· The mechanic shop of our institute has tailor-made a superb monel 1 L-autoclave according to our plans. This equipment allows us to carry out pressure reactions with corrosive gases or liquids such as hydrogen fluoride and sulfur tetrafluoride. In this way, many new compounds have been prepared, among them derivatives harboring the 1-(trifluoromethyl)cyclopropyl group, an isosteric, but metabolically stable analog of the tert-butyl group.
· 'Aryne' mechanisms have been studied and exploited to realize cascade substitutions of the halogen atoms in 1,3,5-trifluorobenzene and to open selective entries to naphthalene derivatives bearing trifluoromethyl and trifluoromethoxy groups at sensitive positions.
· Molecular 'scaffolds' have been developed on the basis of iodo(bromo)chloropyridines to facilitate the assembly of functional subunits and to optimize their binding to enzymes or receptors.
· Regioflexible organometallic methods have been employed to create a wealth of pharmaceutically attractive key intermediates from simple starting materials such as F-, F3C- and F3CO-substituted phenols, benzyl alcohols, phenethyl alcohols, anilines and benzyl amines.
· Pyridines and quinolines carrying simultaneously bromo and trifluoromethyl substituents were converted into whole populations of functionalized derivatives which are promising candidates for application in the agricultural area.

Datenbankreferenzen (Englisch)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 97.0083