title: Enantioselective synthesis of spliceostatin E and evaluation of biological activity.
abstract: An enantioselective total synthesis of spliceostatin E has been accomplished. The δ-lactone unit A was constructed from readily available (R)-glycidyl alcohol using a ring-closing olefin metathesis as the key reaction. A cross-metathesis of ring A containing δ-lactone and the functionalized tetrahydropyran B-ring provided spliceostatin E. Our biological evaluation of synthetic spliceostatin E revealed that it does not inhibit splicing in vitro and does not impact speckle morphology in cells. Spliceostatin E was reported to possess potent antitumor activity.
authors.affiliation: †Department of Chemistry and Department of Medicinal Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ghosh
authors.affiliation: †Department of Chemistry and Department of Medicinal Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Veitschegger
authors.affiliation: †Department of Chemistry and Department of Medicinal Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907, United States.
authors.forename: Venkata Reddy
authors.initials: VR
authors.lastname: Sheri
authors.affiliation: ‡Department of Molecular Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California, Santa Cruz, California 95064, United States.
authors.forename: Kerstin A
authors.initials: KA
authors.lastname: Effenberger
authors.affiliation: ‡Department of Molecular Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California, Santa Cruz, California 95064, United States.
authors.forename: Beth E
authors.initials: BE
authors.lastname: Prichard
authors.affiliation: ‡Department of Molecular Cell and Developmental Biology and Center for Molecular Biology of RNA, University of California, Santa Cruz, California 95064, United States.
authors.forename: Melissa S
authors.initials: MS
authors.lastname: Jurica
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D011714:Pyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D011714:Pyrans; D011753:Pyrones; D013141:Spiro Compounds; C553684:spliceostatin A; C000596810:spliceostatin E