313692-35-2Relevant academic research and scientific papers
Development of synthetic methodology suitable for the radiosynthesis of combretastatin A-1 (CA1) and its corresponding prodrug CA1P
Shirali, Anupama,Sriram, Madhavi,Hall, John J.,Nguyen, Benson L.,Guddneppanavar, Rajsekhar,Hadimani, Mallinath B.,Ackley, J. Freeland,Siles, Rogelio,Jelinek, Christopher J.,Arthasery, Phyllis,Brown, Rodney C.,Murrell, Victor Leon,McMordie, Austin,Sharma, Suman,Chaplin, David J.,Pinney, Kevin G.
experimental part, p. 414 - 421 (2009/12/05)
Synthetic methodology has been established suitable for the preparation of combretastatin A-1 (CA1) and its corresponding phosphate prodrug salt (CA1P) in high specific activity radiolabeled form. Judicious selection of appropriate phenolic protecting groups to distinguish positions on the A-ring from the B-ring of the stilbenoid was paramount for the success of this project. Methylation of the C-4' phenolic moiety by removal of the tert- butyldimethylsilyl protecting group in the presence of methyl iodide was accomplished in excellent yield without significant Z to E isomerization. This step (carried out with 12C-methyl iodide as proof of concept in this study) represents the process in which a 14C radioisotope could be incorporated in an actual radiosynthesis. CA1 is a natural product isolated from the African bush willow tree (Combretum caffrum) that has important medicinal value due, in part, to its ability to inhibit tubulin assembly. As a prodrug, CA1P (OXi4503) is in human clinical trials as a vascular disrupting agent.
