An efficient synthetic strategy for obtaining 4-methoxy carbon isotope labeled combretastatin A-4 phosphate and other Z-combretastatins.
Human cancer and other clinical trials under development employing combretastatin A-4 phosphate (1b, CA4P) should benefit from the availability of a [(11)C]-labeled derivative for positron emission tomography (PET). In order to obtain a suitable precursor for addition of a [(11)C]methyl group at the penultimate step, several new synthetic pathways to CA4P were evaluated. Geometrical isomerization (Z to E) proved to be a challenge, but it was overcome by development of a new CA4P synthesis suitable for 4-methoxy isotope labeling.
Pettit
George R
GR
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287-1604, USA. bpettit@asu.edu
Minardi
Mathew D
MD
Hogan
Fiona
F
Price
Pat M
PM
D001632:Bibenzyls / Q000138:chemical synthesis* / Q000737:chemistry; D007553:Isotope Labeling; D015394:Molecular Structure; D049268:Positron-Emission Tomography; D013237:Stereoisomerism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry
D001632:Bibenzyls; D013267:Stilbenes; C040105:combretastatin; C058728:fosbretabulin