A direct and efficient total synthesis of the tubulin-binding agents ceratamine A and B; use of IBX for a remarkable heterocycle dehydrogenation.
The total synthesis of the tubulin-binding agents ceratamine A and B is reported, along with des-methyl analogs, via a synthetic route that is high-yielding and operationally efficient. The synthetic route involved a Beckmann rearrangement to form an azepine ring precursor, a Knoevenagel condensation to install the benzylic side chain, and an effective imidazole annulation onto an alpha-aminoketone precursor with a protected S-methylisothiourea. Final dehydrogenation proved remarkably facile using IBX.
Coleman
Robert S
RS
Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, USA. coleman@chemistry.ohio-state.edu
Campbell
Erica L
EL
Carper
Daniel J
DJ
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007462:Iodobenzenes / Q000737:chemistry*; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D001381:Azepines; D007093:Imidazoles; D007462:Iodobenzenes; D050257:Tubulin Modulators; C485389:ceratamine A; C485390:ceratamine B; C476101:o-iodoxybenzoic acid