Synthesis of novel 11-desmethyl analogues of laulimalide by Nozaki-Kishi coupling.
As a first entry into structurally simplified analogues of the anticancer agent laulimalide, 11-desmethyl compounds 2 and 3 were selected by molecular modeling. The unfavorable diastereoselectivity in the key synthetic step, a Nozaki-Kishi coupling between macrocyclic aldehyde 4 and vinyl iodide 5, was overcome either by use of catalytic amounts of DIANANE-type ligands or L-Selectride reduction of the derived enone. This methodology should allow modular introduction of other, unnatural, side chains. [reaction: see text]
Paterson
Ian
I
University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, U.K. ip100@cam.ac.uk
Bergmann
Hermann
H
Menche
Dirk
D
Berkessel
Albrecht
A
D000447:Aldehydes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D006571:Heterocyclic Compounds / Q000737:chemistry; D008024:Ligands; D018942:Macrolides; D008956:Models, Chemical; D013237:Stereoisomerism; D043823:Taxoids / Q000138:chemical synthesis* / Q000494:pharmacology; D014753:Vinyl Compounds / Q000737:chemistry
D000447:Aldehydes; D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D008024:Ligands; D018942:Macrolides; D043823:Taxoids; D014753:Vinyl Compounds; C117305:laulimalide