Electrolytic Macrocyclizations: Scalable Synthesis of a Diazonamide-Based Drug Development Candidate

An electrochemical method to synthesize the core macrolactam of diazonamides is described. Large ring‐forming dehydrogenation is initiated by anodic oxidation at a graphite surface. The reaction requires no tailoring of the substrate and occurs at ambient temperature in aqueous DMF in an undivided c...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2015-04, Vol.54 (16), p.4818-4822
Main Authors: Ding, Hui, DeRoy, Patrick L., Perreault, Christian, Larivée, Alexandre, Siddiqui, Arshad, Caldwell, Charles G., Harran, Susan, Harran, Patrick G.
Format: Article
Language:English
Subjects:
Ambient temperature
Amides - chemical synthesis
Amides - chemistry
Analogue
anodic oxidation
Anodizing
Azo Compounds - chemistry
Cancer
Crystallography, X-Ray
Cyclization
Dehydrogenation
Electrolytic cells
electrosynthesis
Forming
Graphite
Graphite - chemistry
Lactams, Macrocyclic - chemical synthesis
Lactams, Macrocyclic - chemistry
macrocycles
Macrocyclic compounds
Molecular Conformation
natural products
oxazoles
Oxazoles - chemical synthesis
Oxazoles - chemistry
Oxidation-Reduction
Pharmaceutical Preparations - chemistry
Surface Properties
Synthesis
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Summary:An electrochemical method to synthesize the core macrolactam of diazonamides is described. Large ring‐forming dehydrogenation is initiated by anodic oxidation at a graphite surface. The reaction requires no tailoring of the substrate and occurs at ambient temperature in aqueous DMF in an undivided cell open to air. This unique chemistry has enabled a concise, scalable preparation of DZ‐2384; a refined analog of diazonamide A slated for clinical development as a cancer therapeutic. Electrifying chemistry! The core macrolactam of diazonamides can be synthesized electrochemically. This large ring forming dehydrogenation has enabled a concise preparation of DZ‐2384, a refined analogue of diazonamide A slated for clinical development as a cancer therapeutic.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201411663