Formal enantioselective synthesis of (+)-compactin.
[reaction: see text] The challenging structural features and important biological activity of (+)-compactin (1) explain the substantial synthetic interest that it has generated. We report a novel enantioselective approach to the advanced intermediate 2a, which constitutes a formal synthesis of (+)-1. The sequence utilizes MacMillan's organocatalytic Mukaiyama-Michael reaction, which stereoselectively adds the silyloxyfuran 6 to alpha,beta-unsaturated aldehyde 7. The chirality generated in this reaction guides the formation of the other three consecutive stereocenters found in 2a.
Merck Frosst Canada Ltd., 16711 Trans Canada Highway, Kirkland, Québec H9H 3L1, Canada. joel_robichaud@merck.com
Joël
J
Robichaud
François
F
Tremblay
D003500:Cyclization; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C012258:mevastatin; D008148:Lovastatin