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Synthesis of double carbon‐14 labeled CI‐937 1 and CI‐942, potential new anticancer drugs
Author(s) -
Hicks James L.,
Huang C. C.,
Showalter H. D. Hollis
Publication year - 1987
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.2580241008
Subject(s) - chemistry , phthalic anhydride , benzoic acid , acylation , carboxylation , amide , hydrolysis , friedel–crafts reaction , medicinal chemistry , organic chemistry , catalysis
CI‐937 and CI‐942, compounds which show potent anticancer activity, were synthesized with double labeled high specific activity carbon‐14. The key intermdiate in the synthesis, 3,6‐dichloro‐[dicarbonyl‐ 14 C 2 ]phthalic anhydride was made by treating 2‐bromo‐1,4‐dichlorobenzene with n‐butyllithium and 14 CO 2 to give 2,5‐dichloro[carboxy‐ 14 C]benzoic acid, which was converted to its diethylamide. Ortho‐directed lithiation followed by a second carboxylation produced the ortho acid‐amide. Hydrolysis and dehydration generated the anhydride. Friedel‐Crafts acylation of the anhydride with 1,4‐benzenediol gave 1,4‐dichloro‐5,8‐dihydroxy[9,10‐ 14 C 2 ]‐9,10‐anthracenedione. Protection and hydrazination gave a chloroanthrapyrazole intermediate which was converted into [ 14 C 2 ]CI‐937 or [ 14 C 2 ]CI‐942 in two steps. The specific activities of the final compounds were 196 μCi/mg and 182 μCi/mg respectively.