Cheng L, Remers W A
J Med Chem. 1977 Jun;20(6):767-70. doi: 10.1021/jm00216a006.
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.
发现了一种将丝裂霉素C转化为N - 甲基丝裂霉素A的有效方法。后一种化合物在酸性水解时仅产生两种产物，即顺式和反式-1-羟基-7-甲氧基-2-甲基氨基丝裂霉素。这种选择性使得顺反比例能够定量测定为4:1。鉴于在简单氮丙啶开环时得到反式立体化学结构，这种顺式异构体的优势出乎意料。为了确定丝裂霉素的9a - 甲氧基是否控制氮丙啶环的开环方向，制备了缺乏该取代基的7 - 甲氧基-1,2-(N - 甲基氮丙啶基)丝裂霉素并在酸性条件下水解。它产生了相同的两种产物，顺反比例为3:1。在大肠杆菌中诱导λ噬菌体时，顺式-1-羟基-7-甲氧基-2-甲基氨基丝裂霉素比相应的反式异构体更具活性，但这两种化合物的活性均低于氮丙啶丝裂霉素或丝裂霉素。丝裂霉素A、丝裂霉素C和N - 甲基丝裂霉素A对小鼠P388白血病有活性。
