Pharmacophore mapping in the laulimalide series: total synthesis of a vinylogue for a late-stage metathesis diversification strategy.
An efficient synthesis of the macrocyclic core of laulimalide with a pendant vinyl group at C20 is described, allowing for late-stage introduction of various side chains through a selective and efficient cross metathesis diversification step. Representative analogues reported herein are the first to contain modifications to only the side chain dihydropyran of laulimalide and des-epoxy laulimalide. This step-economical strategy enables the rapid synthesis of new analogues using alkenes as an inexpensive, abundantly available diversification feedstock.
Wender
Paul A
PA
Departments of Chemistry and Molecular Pharmacology, Stanford University, Stanford, CA 94305-5080, USA. wenderp@stanford.edu
Hilinski
Michael K
MK
Skaanderup
Philip R
PR
Soldermann
Nicolas G
NG
Mooberry
Susan L
SL
D047028:Macrocyclic Compounds / Q000138:chemical synthesis*; D018942:Macrolides; D015394:Molecular Structure; D043823:Taxoids / Q000737:chemistry*
D047028:Macrocyclic Compounds; D018942:Macrolides; D043823:Taxoids; C117305:laulimalide