4-Hydroperoxidation in the Fenton oxidation of the antitumor agent cyclophosphamide

Abstract

CH5) and (C7H7+ -CH3), are shifted to higher masses in the spectrum of C7H4D3+ from p-CD3C6H4N02 (Figure 1G), strongly supporting the tolyl structure 3 as the major form of these ions.19Although appearance potentials indicate that C7H7+ ions from m-and p-CH3C6H4Br and o-and m-CHr C6H4I have structure 3 on formation,5 their CA spectra show that only the ions formed from the iodo compounds have retained this structure for 10-5 sec. Similarly, in contrast to previous conclusions,6 our data indicate that ions of structure 3, not 1, are formed from p-c H3C6H4COCH3.(19) However, we find for P-CD3C6H4NO2 and P-CH3C6D4NO2 that the metastable decompositions used in the previous study6 involve complete H/D scrambling, indicating that the differences noted by these authors are due to differences in ion internal energy, not to differences in ion structure.9•16 (20) Postdoctoral fellow supported by grants from the National Institutes of Health and the Army Research Office, Durham.

Comparison of TiO2 photocatalysis, electrochemically assisted Fenton reaction and direct electrochemistry for simulation of phase I metabolism reactions of drugs

“…The mechanisms of CYP450-catalysed reactions, such as hydroxylation, dehydrogenation, and heteroatom oxidation and dealkylation, depend on the chemical structure of a particular substrate and the enzyme isoform involved to the metabolic reactions (For extensive reviews, see Guengerich, 2001;Meunier et al, 2004). Even though the exact reaction mechanism may differ from the enzymatic route, many CYP450 reactions can be simulated by non-enzymatic oxidation methods, such as electrochemical oxidation (Johansson et al, 2007;Jurva et al, 2003), Fenton reaction (Liang et al, 2013;Van der Steen et al, 1973;Zbaida et al, 1986Zbaida et al, , 1987 and titanium dioxide (TiO 2 ) photocatalysis (Calza et al, 2004;Nissilä et al, 2011), which have been proposed as affordable and convenient alternatives to the traditional in vitro experiments in the early preclinical phase of metabolite screening.…”

Ulicyclamide and ulithiacyclamide, two new small peptides from a marine tunicate

“…H (CDC13, 220 MHz) ( ) 4.82 (dq, 7=4, 7 Hz) 2.1 (m, 2 H) 0.85 (t, 3 H,7 = 7 Hz) 7.85 (d,7 = 10 Hz) 4.52 (t,7 = 8 Hz) 1.9 (m, 2 H) 0.73 (d, 3 H,7= 7 Hz) 7.30 (s, 5 H) 4.26 (d, 7 = 4 Hz) 1.71 (d, 3 H, 7 = 7 Hz) °Carbon assignments are based on literature values for amino acids and on values measured for the synthetic thiazole model compound.…”

Synthesis of cyclophosphamide metabolites by a peroxygenase from Marasmius rotula for toxicological studies on human cancer cells

“…PPA can be produced by Fenton oxidation of CPA, which uses Fe 2+ ions as iron(II) sulphate and hydrogen peroxide in an acidic solution. This oxidation method achieved a yield of only 3–4% PPA and 11% 4-keto-CPA (van der Steen et al, 1973 ). Direct ozonation of cyclophosphamide or of O -3-butenyl- N , N -bis(2-chloroethyl)-phosphordamidate is another option for PPA synthesis in only one step.…”