40277-05-2Relevant articles and documents
4 Hydroxycyclophosphamide anhydro dimer: revised structure of the Fenton oxidation product of cyclophosphamide
Takamizawa,Matsumoto,Iwata
, p. 517 - 520,518, 519 (1974)
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Oxime derivatives of the intermediary oncostatic metabolites of cyclophosphamide and ifosfamide: Synthesis and deuterium labeling for applications to metabolite quantification
Ludeman,Shulman-Roskes,Wong,Han,Anderson,Strong,Colvin
, p. 393 - 398 (1995)
There is ongoing interest in the selective, quantitative analysis of the cyclophosphamide metabolites 4-hydroxycyclophosphamide (2a) and aldophosphamide (3a) because these tautomers are generally believed to play a key role in oncostatic selectivity and metabolite transport. O-(2,3,4,5,6- Pentafluorobenzyl)hydroxylamine (C6F5CH2ONH2, 1 equiv) provided for the complete conversion (by 31P NMR, 60% reaction within 15 min at 20 °C) of 2a/3a (17 mM in H2O/CH3OH) to E/Z-aldophosphamide O-(2,3,4,5,6- pentafluorobenzyl)oxime [C6F5CH2ON=CHCH2CH2OP-(O)(NH2)N(CH2CH2Cl)2; E:Z = 54:46 (±3% average deviation)]. Under these conditions, the oxime exhibited little (6%) decomposition over 3 weeks. Parallel studies showed that 4-hydroxyifosfamide/aldoifosfamide reacted completely to give the analogous aldoifosfamide oxime [C6F5- CH2ON=CHCH2CH2OP(O)(NHCH2CH2Cl)2; E:Z = 52:48 (±1% average deviation)] with 50% reaction within 15 min at 20 °C with no product decomposition over 3 weeks. In aqueous methanol and with 2 equiv C6F5CH2ONH2, clinically useful 4-hydroperoxycyclophosphamide (10 mM; τ = 10 min, 37 °C) and its isomer 4-hydroperoxyifosfamide (10 mM; τ = 25 min, 20 °C) underwent complete conversion to the corresponding aldehyde oximes. Each oxime was synthesized with deuterium in the chloroethyl moieties for use as internal standards in GC/MS applications.
4-Peroxycyclophosphamide use thereof
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Page/Page column 2, (2010/09/18)
4-Peroxycyclophosphamide is provided along with its method of preparation. The compound is useful for treating human cancer, particularly human primary and metastatic malignant brain tumors.
The Mechanism of Activation of 4-Hydroxycyclophosphamide
Borch, Richard F.,Millard, Jo Ann
, p. 427 - 431 (2007/10/02)
4-Hydroxycyclophosphamide (2/3) of unknown stereochemistry is the initial metabolite formed after administration of cyclophosphamide (1).Ultimate conversion to the cytotoxic metabolite phosphoramide mustard (6) is initiated by ring opennig of 4-hydroxycyclophosphamide to produce aldophosphamide (4).The ring-opennig reaction and subsequent equilibration of 2-4 are subject to general-acid catalysis, and the equilibrium composition is independent of buffer structure and pH.In contrast, formation of 6 from 4 proceeds by general-base-catalyzed β-elimination. trans-4-Hydroxycyclophosphamide undergoes ring opening ca. 4 times faster than the cis isomer, and cyclization of 4 favors the trans isomer by a factor of ca. 3 over the cis isomer.The rapid equilibration of 2-5 and the absence of elimination to give 6 at pH ca. 5 provides a convenient method to prepare a stable equilibrium mixture of activated cyclophosphamide metabolites suitable for in vitro use.
