Alkylating properties of phosphoramide mustard.
Alkylating properties of phosphoramide mustard.
复制标题
磷酰胺芥末的烷基化特性。
作者：
M. Colvin;R. Brundrett;M. N. Kan;I. Jardine;C. Fenselau
环磷酰胺、磷酰胺芥末和去甲氮芥这两种细胞毒性代谢物的相对烷基化活性已在 pH 4.6 和 7.4 下进行了研究。这些代谢物对乙硫醇进行烷基化形成的产物已得到鉴定，证实磷酰胺芥子气作为完整分子进行烷基化反应。已经合成了两种代谢物的氘代类似物，即 N,N-双(2,2-二氘代-2-氯乙基)-磷二酰胺酸和 N,N-双(2,2-二氘代-2-氯乙基)胺，并用于确定烷基化直接通过氮丙啶鎓中间体进行，而不是直接通过 SN2 置换氯原子。
The relative alkylating activities of two of the cytotoxic metabolites of cyclophosphamide, phosphoramide mustard and nornitrogen mustard, have been studied at pH 4.6 and 7.4. The products formed on alkylation of ethanethiol by these metabolites have been identified, confirming that phosphoramide mustard undergoes alkylation reactions as an intact molecule. Deuterated analogs of the two metabolites have been synthesized, namely N,N-bis(2,2-dideutero-2-chloroethyl)-phosphorodiamidic acid and N,N-bis(2,2-dideutero-2-chloroethyl)amine and used to determine that alkylation proceeds directly via an aziridinium intermediate rather than a direct SN2 displacement of the chlorine atom.