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 IC₅₀ up to 60 nM