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

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.

SUBMITTER: Ghosh AK

PROVIDER: S-EPMC5333946 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Ghosh Arun K AK Lv Kai K Ma Nianchun N Cárdenas Emilio L EL Effenberger Kerstin A KA Jurica Melissa S MS

Organic & biomolecular chemistry 20160518 23

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 ...[more]

PMID: 27188838

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