Total synthesis of murisolins and evaluation of tumor-growth inhibitory activity.
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.
Maezaki
Naoyoshi
N
Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Japan.
Tominaga
Hiroaki
H
Kojima
Naoto
N
Yanai
Minori
M
Urabe
Daisuke
D
Ueki
Risa
R
Tanaka
Tetsuaki
T
Yamori
Takao
T
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
D000480:Alkynes; D000970:Antineoplastic Agents; D005663:Furans; D007202:Indicators and Reagents; D007783:Lactones; C507543:murisolin