title: Chemo- and Regioselective Functionalization of Nortrilobolide: Application for Semisynthesis of the Natural Product 2-Acetoxytrilobolide.
abstract: The difference in reactivity of the hexaoxygenated natural product thapsigargin (1) and the pentaoxygenated nortrilobolide (3) was compared in order to develop a chemo- and regioselective method for the conversion of nortrilobolide (3) into the natural product 2-acetoxytrilobolide (4). For the first time, a stereoselective synthesis of 2-acetoxytrilobolide (4) is described, which involves two key reactions: the first chemical step was a one-pot substitution-oxidation reaction of an allylic ester into its corresponding α,β-unsaturated ketone. The second process consisted of a stereoselective α'-acyloxylation of the key intermediate α,β-unsaturated ketone to afford its corresponding acetoxyketone, which was converted into 2-acetoxytrilobolide (4) in a few steps. This innovative approach would allow the synthesis of a broad library of novel and valuable penta- and hexaoxygenated guaianolides as potential anticancer agents.
authors.affiliation: †Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
authors.forename: Nhu Thi Quynh
authors.initials: NT
authors.lastname: Doan
authors.affiliation: †Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
authors.forename: François
authors.initials: F
authors.lastname: Crestey
authors.affiliation: ‡Department of Plant and Environmental Sciences, Faculty of Science, University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C, Denmark.
authors.forename: Carl Erik
authors.initials: CE
authors.lastname: Olsen
authors.affiliation: †Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen Ø, Denmark.
authors.forename: Søren Brøgger
authors.initials: SB
authors.lastname: Christensen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D052176:Azulenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D045789:Sesquiterpenes, Guaiane / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D053629:Thapsia / Q000737:chemistry*; D019284:Thapsigargin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: C000601157:2-acetoxytrilobolide; D000970:Antineoplastic Agents; D052176:Azulenes; D045789:Sesquiterpenes, Guaiane; C070242:nortrilobolide; D019284:Thapsigargin