Synthesis of fluorine containing analogues of natural products
In last decades, fluorine is recognized as the second favorite heteroatom in current drug design, after nitrogen. Following this paradigm, e.g. the replacement of a C-H or C=O bond with a C-F bond in biologically active compounds frequently introduce beneficial properties such as higher metabolic stability, increased binding to target proteins, and increased membrane permeability. Thus most of the Active Pharmaceutical Ingredients (API) under development contain fluorine, i.e. these molecules have C(sp3)-F, C(Ar)-F, C(HetAr)-F, C(sp3)-CF3, C(Ar)-CF3, C(HetAr)-CF3 moieties.
For these reasons, the synthesis of fluorinated analogues of biologically active natural products (`Fluorine mapping`) is an important and interesting field. In order to find the molecular structure having optimal biological effect, we plan to prepare natural products with fluorine containing functional groups (eg, F, CF3, CH2CF3) at different positions, and then biological tests in collaboration.
Naturally occurring alkaloids can be useful molecules in drug development. Thus, in the first part of our synthetic work, we plan to implement modifications of the isoquinoline alkaloids commonly used in the pharmaceutical industry (e.g. apomorphine 1, Parkinson`s disease; berberine 2, type 2 diabetes; cherylline 3).
During designing of the syntheses, it is another important aspect to develop environmentally friendly, cost effective and easy-to-scale-up synthetic routes.
The compounds prepared can also be used as building blocks for molecules with more complex structure.
Dénes Szabó, Anikó Nemes