Improved synthesis of epothilone B employing alkylation of an alkyne for assembly of subunits.
[formula: see text] A strategy for assembling the two principal modules of epothilone B was developed that merges an allylic bromide with a terminal acetylene to fabricate the C10-C11 bond of the macrocycle. The resulting alkyne was semihydrogenated to give a seco ester previously employed in our total synthesis of epothilone B. This new approach affords a more efficient route to the naturally occurring macrolide and to its 9,10-dehydro analogue.
White
J D
JD
Department of Chemistry, Oregon State University, Corvallis 97331-4003, USA. james.white@orst.edu
Sundermann
K F
KF
Carter
R G
RG
D000478:Alkylation; D000480:Alkynes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D034261:Epothilones; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry
D000480:Alkynes; D000970:Antineoplastic Agents; D034261:Epothilones; D004852:Epoxy Compounds; D013844:Thiazoles; C093788:epothilone B