Methylenedioxy ring cleavage

K Zhang, F Lepage, G Cuvier, J Astoin, MS Rashed, TA Baillie. The metabolic fate of stiripentol in the rat. Studies on cytochrome P-450-mediated methylenedioxy ring cleavage and side chain isomerism. Drug Metab Dispos 18 794, 1990. 

Methylenedioxy (Benzodioxole) Ring Cleavage. Methylenedioxy-phenyl compounds, such as safrole or the insecticide synergist, piperonyl butoxide, many of which are effective inhibitors of CYP monooxygenations, are themselves metabolized to catechols. The most probable mechanism appears to be an attack on the methylene carbon, followed by elimination of water to yield a carbene. The highly reactive carbene either reacts with the heme iron to form a CYP-inhibitory complex or breaks down to yield the catechol (Figure 7.8). 

This new procedure is especially valuable in the synthesis of benzoxazinones bearing one or two methoxy substituents or a 6,7-methylenedioxy unit at the aromatic ring. A drawback of the former methyl acetal cleavage method (Fig. (7), [110]) consisted in an insufficient selectivity of the boron trichloride mediated 2-methoxy group... 

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