Synthesis of 14C labelled electrophilic ligands of the colchicine binding site of tubulin: Chloroacetates of demethylthiocolchicines and of N‐acetylcolchinol; isothiocyanate of 9‐deoxy‐N‐acetylcolchinol

Abstract 14C‐Chloroacetates of 2‐demethylthiocolchicine 7 (specific activity 55.0 mCi/mmol, radiochemical yield 26.1%), and of 3‐demethylthiocolchicine 8 (specific activity 55.0 mCi/mmol, radiochemical yield 5.7%) were synthesized and found to covalently bind with high specificity to the β‐subunit of tubulin. The 14C‐chloroacetate of N‐acetylcolchinol 5 (specific activity 56.0 mCi/mmol, radiochemical yield 7.8%) and the 14C‐isothiocyanate 6 (specific activity 50.0 mCi/mmol, radiochemical yield 32%) were also prepared and found to react covalently with tubulin but in a nonspecific manner. With the radiolabelled chloroacetates 7 and 8 two compounds are now available to further characterize the colchicine binding site on the β subunit of tubulin.