Synthesis and Structure‒Activity Relation Studies of Cytotoxic Epoxide Derivatives of 7-Oxabicyclo[2.2.1]heptane

Dimethyl exo-5,6-oxido-7-oxabicyclo[2.2.1]hept-2-ene-2,3-dicarboxylate (1) and the 1-methyl homologue 2 were shown to exhibit significant cytotoxicity in the 9KB tissue culture assay. Several analogues of 1 were prepared and it was found that removal of the epoxide, or the oxygen bridge, or the 2,3 double bond from 1 resulted in loss of significant cytotoxic activity. One compound which lacked the epoxide moiety, dimethyl 1-methyl-7-oxabicyclo[2.2.1]hepta-2,5-diene-2,3-dicarboxylate (5), also exhibited marginal cytotoxic activity.