Alkene-alkyne coupling as a linchpin: an efficient and convergent synthesis of amphidinolide P.
A short and efficient synthesis of the cytotoxic macrolide amphidinolide P is described. A remarkably chemo- and regioselective ruthenium-catalyzed alkene-alkyne coupling allows for a convergent synthesis and demonstrates that both enynes and beta-lactones are suitable coupling partners. This work also features a novel strategy for the preparation of macrolactones via intramolecular transesterification of beta-lactones. The target structure was prepared in 15 steps for the longest linear sequence and 10% overall yield, 24 steps total.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, California 94305-5080, USA. bmtrost@stanford.edu
Papillon
Julien P N
JP
D000475:Alkenes / Q000737:chemistry*; D000480:Alkynes / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D018942:Macrolides; D000097442:Amphidinolides
D000475:Alkenes; D000480:Alkynes; D006571:Heterocyclic Compounds; D018942:Macrolides; C407987:amphidinolide P; D000097442:Amphidinolides