Comparative stereochemistry in the aziridine ring openings of N-methylmitomycin A and 7-methoxy-1,2-(N-methylaziridino)mitosene.
A useful method was found for the conversion of mitomycin C into N-methylmitomycin A. The latter compound gave only two products on acid hydrolysis, the cis- and trans-1-hydroxy-7-methoxy-2-methylaminomitosenes. This selectivity allowed the cis--trans ratio to be quantitatively determined as 4:1. Such a predominance of the cis isomer is unexpected in view of the trans stereochemistry obtained in the opening of simple aziridines. In order to determine if the 9a-methoxy group of mitomycins controlled the direction of aziridine ring opening 7-methoxy-1,2-(N-methylaziridino)mitosene, which lacks this substituent, was prepared and hydrolyzed in acid. It gave the same two products in a 3:1 cis-trans ratio. In the induction of lambda-bacteriophage in Escherichia coli cis-1-hydroxy-7-methoxy-2-methylaminomitosene was more active than the corresponding trans isomer, but both of these compounds were less active than the aziridinomitosene or the mitomycins. Mitomycin A, mitomycin C, and N-methylmitomycin A were active against P388 leukemia in mice.
D000818:Animals; D001388:Aziridines / Q000494:pharmacology / Q000627:therapeutic use; D001389:Azirines / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D003090:Coliphages / Q000187:drug effects / Q000502:physiology; D006868:Hydrolysis; D007942:Leukemia, Experimental / Q000188:drug therapy; D008297:Male; D051379:Mice; D008937:Mitomycins / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D008968:Molecular Conformation; D013237:Stereoisomerism
D001388:Aziridines; D001389:Azirines; D008937:Mitomycins; C014675:N-methylmitomycin A