title: Total synthesis of murisolins and evaluation of tumor-growth inhibitory activity.
abstract: Convergent total syntheses of murisolin (1), natural 16,19-cis-murisolin 2, and unnatural 16,19-cis-murisolin 3 were accomplished by asymmetric alkynylation of alpha-tetrahydrofuranic aldehyde with a diyne and Sonogashira coupling with a gamma-lactone segment as the key steps. Stereoisomers of alpha-tetrahydrofuranic aldehyde were synthesized with high optical purity and the asymmetric alkynylation of these with 1,6-heptadiyne proceeded in good yield and with high diastereoselectivity. The cell-growth inhibition profile and COMPARE analysis of the synthetic compounds 1-3 were also investigated.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Maezaki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tominaga
authors.forename: Naoto
authors.initials: N
authors.lastname: Kojima
authors.forename: Minori
authors.initials: M
authors.lastname: Yanai
authors.forename: Daisuke
authors.initials: D
authors.lastname: Urabe
authors.forename: Risa
authors.initials: R
authors.lastname: Ueki
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takao
authors.initials: T
authors.lastname: Yamori
mesh_terms: D000480:Alkynes / Q000138:chemical synthesis / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D005663:Furans / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013055:Spectrophotometry, Infrared
chemical_list: D000480:Alkynes; D000970:Antineoplastic Agents; D005663:Furans; D007202:Indicators and Reagents; D007783:Lactones; C507543:murisolin