3 research outputs found
Short and Straightforward Enantioselective Synthesis of Both Enantiomers of Mequitazine through Iridium-Catalyzed Asymmetric Hydrogenation of a Nonfunctionalized Cyclic Enamine
International audienceA short and straightforward asymmetric synthesis of both enantiomers of the antihistaminic drug mequitazine is reported. This atom-economical and attractive method features an iridium-catalyzed asymmetric hydrogenation of a nonfunctionalized cyclic enamine as a key step to install the C 3-stereogenic center. After a full investigation of the effects of catalyst precursors, ligands, solvents, temperature, and hydrogen pressure, mequitazine (1) is obtained in good yield (up to 80%) and with acceptable enantiomeric excesses up to 47%
Synthesis and Antiproliferative and Metabolic Evaluations of Novel Securinine Derivatives
New securinine analogues have been
prepared by semisynthesis. Two
series were developed using either Suzuki or Sonogashira cross coupling
reactions. The <i>in vitro</i> cytotoxicity of the compounds
was assayed against HCT-116 colon cancer cells. The most potent derivatives
showed promising growth inhibition on four tumoral cell lines giving
a valuable insight on the structure–activity relationship (SAR)
of securinine. Moreover, high antiproliferative effect against A-375
(melanoma) was observed with IC<sub>50</sub> up to 60 nM