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Electrolytic Macrocyclizations: Scalable Synthesis of a Diazonamide‐Based Drug Development Candidate |
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| Authors: | Dr Hui Ding Patrick L DeRoy Christian Perreault Dr Alexandre Larivée Dr Arshad Siddiqui Dr Charles G Caldwell Susan Harran Prof?Dr Patrick G Harran |
| Institution: | 1. Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, California 90095‐1569 (USA);2. Paraza Pharma Inc. 7171, Frédérick‐Banting, Montréal, QC, H4S 1Z9 (Canada);3. Joyant Pharmaceuticals, 2600 North Stemmons Freeway, Dallas, TX 75207‐2113 (USA) |
| Abstract: | 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. |
| Keywords: | anodic oxidation electrosynthesis macrocycles natural products oxazoles |