The Total Synthesis of (+)-Migrastatin

2003/04/25 by Christoph Gaul, Jón T. Njardarson, Samuel J. Danishefsky · 7 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · #Aldehyde #Aldol condensation #Aldol reaction #Alkene #Catalysis #Chemical Synthesis and Analysis #Chemistry #Combinatorial chemistry #Diene #Enantioselective synthesis #Lewis acids and bases #Metathesis #Natural product #Organic chemistry #Ring-closing metathesis #Stereocenter #Stereochemistry #Synthesis and Catalytic Reactions #Synthetic Organic Chemistry Methods #Total synthesis

paper · doi:10.1021/ja0349103

openalex publication_date 2003/04/25 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01

Abstract

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.

Citations

• A Rapid Esterification by Means of Mixed Anhydride and Its Application to Large-ring Lactonization

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• Macrocyclization by Ring‐Closing Metathesis in the Total Synthesis of Natural Products: Reaction Conditions and Limitations
• Selective monodeprotection of bis-silyl ethers
• Ring-closing metathesis [wikipedia]