Stereoselective synthesis and anticancer activity of broussonetine analogues

The stereoselective synthesis of two broussonetine analogues 14 center dot HC1 and ent-14 center dot HCl with differing stereochemistry of the polyhydroxylated pyrrolidine core and a simple C-13 alkyl fragment has been achieved. For their construction, the known oxazolidinones 15 and 16 were chosen as appropriate advanced scaffolds. The common hydrophobic side chain was incorporated at an early stage of the synthesis through Grubbs' cross metathesis chemistry. The required pyrrolidine skeleton was then formed by the cyclization of open chain intermediates 17 and 18. Four synthesized compounds were screened in vitro for antiproliferative/cytotoxic activity against six cancer cell lines by MTT assay. Compounds 14 center dot HCl (HeLa and A-549) and ent-14 center dot HCl (Caco-2 and Jurkat) showed comparable or higher potency than conventional anticancer agent cisplatin on at least two evaluated cancer cells, respectively. (C) 2017 Elsevier Ltd. All rights reserved.