Synthesis of Fluorenes with Potential Bioactivities

Aromatic compounds (aminopurine, pyridine, quinoline, fluorene…) are excellent building blocks for the development of new drugs. Fluorenone and Fluorene containing natural products display diverse structural features due to their various ring junctions and chiral centers. Together with potential bioactivities, this family of natural products aroused considerable attention from synthetic chemists. They have interesting physicochemical properties and could be used as fluorescent probes¹. They display also high therapeutic activities as anti-oxidant, anti-bacterial, anti-cancer, anti-malarial, anti-myocardial or anti-Alzheimer^2-7.

For example, Dendroflorin isolated from Dendrobium densiflorum, displays a high antioxidant activity. This compound is cytotoxic at 125.8 µg/mL and have an antimigratory effect at 1.0 µg/mL in 24h for H 460 cells (lungs cancer)³. Some 1,6-disubstituted fluorenones can also induce apoptosis and inhibited the tubulin polymerization in cells. They are active in the range of 0.15 to 0.29 µM for many cancer cells (T47D (breast), HCT 116 (colon), SNU 398 (carcinoma)) and represent thus interesting pharmacophore for the research of new anticancer drugs⁴. Isolated from the radix of Caulophyllum robustum Maxim, Caulophine has an anti-myocardial ischemia activity as a calcium antagonist⁵. Interestingly, some fluorenes have also shown a capacity to reduce the amyloid burden which induces severe neurodegeneration and cognitive deficits in Alzheimer’s disease⁶.

Thus, fluorenes are attractive scaffolds for the design of new therapeutic agents. In our laboratory, we focus in the design and the preparation of novel asymmetric 2,7,9-trisusbtituted fluorenes. Herein, we describe the first steps of a convergent synthesis able to lead to a new library of fluorene enantiopurs with high potential bioactivities.

References

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