Asymmetric synthesis of the fully functional macrolide core of salicylihalamide: remote control of olefin geometry during RCM.
A catalysis-based approach to the core region 24 of the antitumor agents salicylihalamides A and B is reported. Key steps are two asymmetric hydrogenations of beta-keto esters 13 and 16 catalyzed by [(R)-BINAP.RuCl(2)](2).NEt(3) and an RCM-based macrocyclization effected by the NHC-containing ruthenium carbene 21. The stereochemical outcome of the latter reaction is controlled by remote substituents on the phenolic OH group of the cyclization precursor 23.
Fürstner
A
A
Max-Planck-Institut für Kohlenforschung, D-45470 Mülheim/Ruhr, Germany. fuerstner@mpi-muelheim.mpg.de
Thiel
O R
OR
Blanda
G
G
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry*; D011161:Porifera / Q000737:chemistry*
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C410986:salicylihalamide A