Preparation of spin-labeled analogs of the antitumor agents TEPA and thio-TEPA.

In recent years, a considerable amount of work has been done in order to elucidate the role of free radical intermediates in carcinogenesis 3. Particular­ ly, with the EPR technique a series of interesting but controversial results have been obtained 3. As a con­ sequence, to date, no conclusions can be made con­ cerning the role of free radicals and other paramagnetig species during the induction and propagation of tumors 3. However, there is hope that it might be possible to develop the EPR technique into a useful diagnostic tool for detection of tumors 3. Until present, the application of chemotherapy in treatment of cancer has been of modest success4. Nevertheless, in certain types of cancers a consider­ able progress has been achieved, and therefore, there exists a justifiable optimism that with the ad­ vance in better understanding of the mechanisms of initiation and propagation of tumors, more effective drugs can also be devised for treatment of cancers 4. Now we would like to report the synthesis of two new spin-labeled analogs (5, X = 0 and 5, X = S) of the well known antineoplastic drugs TEPA (6, X = 0 ) and Thio-TEPA (6, X = S) 5. It is believed that the new compounds will be of value in cancer research since they possess not only an easily by EPR-detectable label but may also exhibit through the nitroxyl moiety an inhibitory-scavening effect on radicals and/or other paramagnetic species in tumor tissues 6. The synthesis of 5 (X = 0 ) and 5 (X = S) was achieved by a “one-batch” process. Thus, the reac­ tion of a benzene solution of 4-hydroxy-2,2,6,6-