Design, synthesis and in vitro splicing inhibition of desmethyl and carba-derivatives of herboxidiene?

Organic & Biomolecular Chemistry Pub Date: 2016-05-18 DOI: 10.1039/C6OB00725B

Abstract

Herboxidiene is a potent inhibitor of spliceosomes. It exhibits excellent anticancer activity against multiple human cancer cell lines. Herein, we describe an enantioselective synthesis of a desmethyl derivative and the corresponding carba-derivatives of herboxidiene. The synthesis involved Suzuki coupling of a vinyl iodide with boronate as the key reaction. For the synthesis of carba-derivatives, the corresponding optically active cyclohexane-1,3-dicarbonyl derivatives were synthesized using an enantioselective desymmetrization of meso-anhydride. The biological properties of these derivatives were evaluated in an in vitro splicing assay.

Graphical abstract: Design, synthesis and in vitro splicing inhibition of desmethyl and carba-derivatives of herboxidiene
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