The total synthesis of (+)-migrastatin.
The first total synthesis of (+)-migrastatin, a macrolide natural product with interesting antimetastatic properties, has been accomplished. Our concise and flexible approach utilizes a Lewis acid-catalyzed diene aldehyde condensation to install the three contiguous stereocenters and the trisubstituted (Z)-alkene of migrastatin. Construction of the two remaining stereocenters and incorporation of the glutarimide-containing side chain have been achieved via an anti-selective aldol reaction, followed by a Horner-Wadsworth-Emmons olefination. Finally, the assembly of the macrocycle has been realized by a highly (E)-selective ring-closing metathesis.
Gaul
Christoph
C
Laboratory for Bioorganic Chemistry, Sloan-Kettering Institute for Cancer Research, 1275 York Avenue, New York, New York 10021, USA.
Njardarson
Jon T
JT
Danishefsky
Samuel J
SJ
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D007783:Lactones / Q000138:chemical synthesis*; D018942:Macrolides; D010881:Piperidones / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry
D000970:Antineoplastic Agents; D007783:Lactones; D018942:Macrolides; D010881:Piperidones; C418199:migrastatin