title: 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.
authors.affiliation: Department of Chemistry and Department of Medicinal Chemistry, Purdue University, West Lafayette, IN 47907, USA. akghosh@purdue.edu.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Kai
authors.initials: K
authors.lastname: Lv
authors.forename: Nianchun
authors.initials: N
authors.lastname: Ma
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Cárdenas
authors.forename: Kerstin A
authors.initials: KA
authors.lastname: Effenberger
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Jurica
mesh_terms: D001897:Boronic Acids / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D005233:Fatty Alcohols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D012326:RNA Splicing / Q000187:drug effects*; D013237:Stereoisomerism
chemical_list: D001897:Boronic Acids; D005233:Fatty Alcohols; D011714:Pyrans; C076087:herboxidiene