title: Total synthesis of natural and non-natural Δ(5,6)Δ(12,13)-jatrophane diterpenes and their evaluation as MDR modulators.
abstract: We report the details of the total synthesis of natural and non-natural jatropha-5,12-dienes. The successful tactic for the assembly of the strained trans-bicyclo[10.3.0]pentadecane scaffold employed a B-alkyl Suzuki-Miyaura cross-coupling for the formation of the C5/C6 double bond and a ring-closing metathesis for the construction of the C12/C13 double bond. The key step of the synthesis of the cyclopentane fragment, an uncatalyzed intramolecular carbonyl-ene reaction, was studied computationally by DFT calculations. The members of the ensemble of synthetic natural and non-natural jatrophanes were subsequently examined as modulators for the ABCB1, ABCG2, and ABCC1 efflux proteins, which are associated with multidrug resistance in cancer chemotherapy.
authors.affiliation: Technische Universität Dortmund, Fakultät Chemie, D-44227 Dortmund, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Schnabel
authors.forename: Katja
authors.initials: K
authors.lastname: Sterz
authors.forename: Henrik
authors.initials: H
authors.lastname: Müller
authors.forename: Julia
authors.initials: J
authors.lastname: Rehbein
authors.forename: Michael
authors.initials: M
authors.lastname: Wiese
authors.forename: Martin
authors.initials: M
authors.lastname: Hiersemann
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D003432:Cross-Linking Reagents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003500:Cyclization; D003517:Cyclopentanes / Q000737:chemistry*; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D028481:Euphorbia / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010936:Plant Extracts / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D003432:Cross-Linking Reagents; D003517:Cyclopentanes; D004224:Diterpenes; D010936:Plant Extracts; C530345:jatrophane