Total synthesis of the microtubule-stabilizing agent (-)-laulimalide.
[structure: see text] The total synthesis of the potent microtubule-stabilizing anticancer agent (-)-laulimalide has been achieved in 27 steps and 2.9% overall yield. Notable features are the use of Jacobsen HDA chemistry for the enantioselective construction of the side chain dihydropyran, a diastereoselective aldol coupling using chiral boron enolate methodology, a Mitsunobu macrolactonization, and a Sharpless AE to introduce the epoxide onto des-epoxy-laulimalide.
Paterson
I
I
University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK. ip100@cus.cam.ac.uk
De Savi
C
C
Tudge
M
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D018942:Macrolides; D008870:Microtubules / Q000187:drug effects; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D043823:Taxoids
D000970:Antineoplastic Agents; D018942:Macrolides; D043823:Taxoids; C117305:laulimalide; D017239:Paclitaxel