Total synthesis of epothilone E and related side-chain modified analogues via a Stille coupling based strategy.
A Stille coupling strategy has been utilized to complete a total synthesis of epothilone E from vinyl iodide 7 and thiazole-stannane 8h. The central core fragment 7 and its trans-isomer 11 were prepared from triene 15 using ring-closing metathesis (RCM), and were subsequently coupled to a variety of alternative stannanes to provide a library of epothilone analogues 18a-o and 19a-o. The Stille coupling approach was then used to prepare epothilone B analogues from the key macrolactone intermediate 24 which was itself synthesized by a macrolactonization based strategy.
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
K C
KC
Nicolaou
N P
NP
King
M R
MR
Finlay
Y
Y
He
F
F
Roschangar
D
D
Vourloumis
H
H
Vallberg
F
F
Sarabia
S
S
Ninkovic
D
D
Hepworth
D002855:Chromatography, Thin Layer; D034261:Epothilones; D004852:Epoxy Compounds / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008956:Models, Chemical; D013844:Thiazoles / Q000138:chemical synthesis*
D034261:Epothilones; D004852:Epoxy Compounds; D013844:Thiazoles; C121425:epothilone E; C093788:epothilone B