Anne Giraud

Synthesis, Biological Evaluation of 1,1‐Diarylethylenes as a Novel Class of Antimitotic Agents

The cytotoxic activities of 23 new isocombretastatin A derivatives with modifications on the B‐ring were investigated. Several compounds exhibited excellent antiproliferative activity at nanomolar concentrations against a panel of human cancer cell lines. Compounds isoFCA‐4 (2 e), isoCA‐4 (2 k) and isoNH2CA‐4 (2 s) were the most cytotoxic, and strongly inhibited tubulin polymerization with IC50 values of 4, 2 and 1.5 μM, respectively. These derivatives were found to be 10‐fold more active than phenstatin and colchicine with respect to growth inhibition but displayed similar activities as tubulin polymerization inhibitors. In addition, cell cycle arrest in the G2/M phase and subsequent apoptosis was observed in three cancer cell lines when treated with these compounds. The disruptive effect of 2 e, 2 k and 2 s on the vessel‐like structures formed by human umbilical vein endothelial cells (HUVEC) suggest that these compounds may act as vascular disrupting agents. Both compounds 2 k and 2 s have the potential for further prodrug modification and development as vascular disrupting agents for treatment of solid tumors.

Radical reactions leading to substituted coumarins

Abstract The reaction of 4-hydroxycoumarins with a series of quinonic chlorides under photostimulation was shown to provide an efficient approach to 3-alkylated coumarin derivatives. Alkylation reactions of this type proceeded via an electron transfer mechanism (SRN1).

Stereoselective hetero-Diels–Alder reactions: structure determination of new xanthenedione derivatives by NMR spectroscopy and x-ray crystallography

The proton and carbon spectra of chromane derivatives were completely assigned by the use of 1H, 13C and 2D NMR spectroscopy, including NOESY and 2D INADEQUATE. The unambiguous configurational assignments of all regioisomers were achieved via 2D NOESY. The structure of the regioisomer 7A was confirmed using x‐ray diffraction.