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 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.
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles, California 90095-1569 (USA).
Hui
H
Ding
Patrick L
PL
DeRoy
Christian
C
Perreault
Alexandre
A
Larivée
Arshad
A
Siddiqui
Charles G
CG
Caldwell
Susan
S
Harran
Patrick G
PG
Harran
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D001391:Azo Compounds / Q000737:chemistry; D018360:Crystallography, X-Ray; D003500:Cyclization; D006108:Graphite / Q000737:chemistry; D047029:Lactams, Macrocyclic / Q000138:chemical synthesis / Q000737:chemistry*; D008968:Molecular Conformation; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry*; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D013499:Surface Properties
D000577:Amides; D001391:Azo Compounds; C000603931:DZ-2384; D047029:Lactams, Macrocyclic; D010080:Oxazoles; D004364:Pharmaceutical Preparations; D006108:Graphite
anodic oxidation; electrosynthesis; macrocycles; natural products; oxazoles