Brandt J A, Ludeman S M, Zon G, Todhunter J A, Egan W, Dickerson R
J Med Chem. 1981 Dec;24(12):1404-8. doi: 10.1021/jm00144a007.
Hydrogenolysis of 3-(benzyloxy)cyclophosphamide (10) using Pd/C catalyst and ethyl acetate as solvent leads to the formation of 3-hydroxycyclophosphamide (3, approximately 20%) and cyclophosphamide (1, approximately 10%), accompanied by regioselective hydrogen-exchange reactions at the C-4 and C-5 positions in 3 and 1. A variety of oxidizing reagents and liver microsomal incubation failed to provide evidence (31P NMR) for conversion of 1 into 3, whereas identical incubation of 3 led to its reduction to 1. Compound 3 is stable at pH 6.5-8.2, 37 degrees C, and exhibits anticancer activity comparable to 1 when tested against L1210 leukemia in mice. Data are discussed with regard to a previously reported suggestion that metabolism of 1 may involved oxidation to give 3 followed by rearrangement of 3 to 2.
使用钯碳催化剂并以乙酸乙酯作为溶剂对3-(苄氧基)环磷酰胺(10)进行氢解反应，会生成3-羟基环磷酰胺(3，约20%)和环磷酰胺(1，约10%)，同时在3和1的C-4和C-5位会发生区域选择性氢交换反应。各种氧化试剂以及肝微粒体孵育均未能提供(31P NMR)将1转化为3的证据，而对3进行相同的孵育会导致其还原为1。化合物3在pH 6.5 - 8.2、37℃条件下稳定，并且在针对小鼠L1210白血病进行测试时，其抗癌活性与1相当。针对先前报道的关于1的代谢可能涉及氧化生成3随后3重排为2的建议，对相关数据进行了讨论。
