Total synthesis of the antimitotic marine macrolide (-)-leiodermatolide.
Leiodermatolide is an antimitotic macrolide isolated from the marine sponge Leiodermatium sp. whose potentially novel tubulin-targeting mechanism of action makes it an exciting lead for anticancer drug discovery. In pursuit of a sustainable supply, we report a highly stereocontrolled total synthesis (3.2% yield) based on a convergent sequence of palladium-mediated fragment assembly and macrolactonization. Boron-mediated aldol reactions were used to configure the three key fragments 2, 5, and 6 by employing the appropriate enantiomer of the lactate-derived ketone 7.
University Chemical Laboratory, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW (UK) http://www-paterson.ch.cam.ac.uk. ip100@cam.ac.uk.
Ian
I
Paterson
Kenneth K-H
KK
Ng
Simon
S
Williams
David C
DC
Millican
Stephen M
SM
Dalby
D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D011161:Porifera / Q000737:chemistry*; D013237:Stereoisomerism
D050256:Antimitotic Agents; D018942:Macrolides; C559222:leiodermatolide
aldol reaction; antitumor agents; cross-coupling; macrolides; total synthesis