Lown J W, Chauhan S M
J Med Chem. 1981 Mar;24(3):270-9. doi: 10.1021/jm00135a007.
Three examples of the postulated but hitherto unisolated 2-(alkylimino)-3-nitrosooxazolidines (2) have been prepared containing cyclohexyl, trans-4-methylcyclohexyl, and 2-chloroethyl groups at the 2 position, respectively. These compounds correspond to intermediates previously postulated to be formed in the aqueous decomposition of the antitumor agents 1-(2-chloroethyl)-3-cyclohexyl- (CCNU), 1-(2-chloroethyl)-3-(4'-trans-methylcyclohexyl)- (MeCCNU), and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), respectively, Compounds 2 decompose under physiological conditions to give a range of products similar to those formed from the corresponding (2-chloroethyl)nitrosoureas, including the hitherto unrecognized 2-hydroxyethl N-alkylcarbamates (9). Compounds 2a and 2b are converted with hydrochloric acid into CCNU and MeCCNU, respectively, suggesting that 2a and 2b may be reaction intermediates of decomposition. The corresponding 3-alkyl-1-nitroso-1-(2-hydroxyethyl)ureas (4) were characterized and, since they also decompose to give the same products as 2, may arise from the ring opening of 2. The intermediacy of compounds 4 can explain the formation of hydroxyethylated nucleosides isolated by other workers from the reaction of (2-chloroethyl)nitrosoureas on polynucleotides.
已制备出三种假定但迄今尚未分离出来的2-（烷基亚氨基）-3-亚硝基恶唑烷（2）的示例，它们在2位分别含有环己基、反式-4-甲基环己基和2-氯乙基。这些化合物分别对应于先前假定在抗肿瘤药物1-（2-氯乙基）-3-环己基（卡莫司汀，CCNU）、1-（2-氯乙基）-3-（4'-反式甲基环己基）（司莫司汀，MeCCNU）和1,3-双（2-氯乙基）-1-亚硝基脲（卡氮芥，BCNU）的水分解过程中形成的中间体。化合物2在生理条件下分解，产生一系列与由相应的（2-氯乙基）亚硝基脲形成的产物相似的产物，包括迄今未被识别的2-羟乙基N-烷基氨基甲酸酯（9）。化合物2a和2b分别与盐酸反应转化为CCNU和MeCCNU，这表明2a和2b可能是分解的反应中间体。对相应的3-烷基-1-亚硝基-1-（2-羟乙基）脲（4）进行了表征，并且由于它们也分解产生与2相同的产物，可能是由2开环产生的。化合物4作为中间体可以解释其他研究人员从（2-氯乙基）亚硝基脲与多核苷酸的反应中分离出的羟乙基化核苷的形成。
