A direct and efficient total synthesis of the tubulin-binding agents ceratamine A and B; use of IBX for a remarkable heterocycle dehydrogenation

Robert S Coleman; Erica L Campbell; Daniel J Carper

doi:10.1021/ol900709n

A direct and efficient total synthesis of the tubulin-binding agents ceratamine A and B; use of IBX for a remarkable heterocycle dehydrogenation

Org Lett. 2009 May 21;11(10):2133-6. doi: 10.1021/ol900709n.

Authors

Robert S Coleman¹, Erica L Campbell, Daniel J Carper

Affiliation

¹ Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210, USA. coleman@chemistry.ohio-state.edu

PMID: 19385610
DOI: 10.1021/ol900709n

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Azepines / chemical synthesis*
Azepines / chemistry
Azepines / pharmacology
Drug Design
Imidazoles / chemical synthesis*
Imidazoles / chemistry
Imidazoles / pharmacology
Iodobenzenes / chemistry*
Molecular Structure
Porifera / chemistry
Tubulin Modulators / chemical synthesis*
Tubulin Modulators / chemistry
Tubulin Modulators / pharmacology

Substances

Azepines
Imidazoles
Iodobenzenes
Tubulin Modulators
ceratamine A
ceratamine B
o-iodoxybenzoic acid

Grants and funding

T32 GM08512/GM/NIGMS NIH HHS/United States