Carbamazepine oxidation catalyzed by manganese porphyrins: Effects of the β-bromination of the macrocycle and the choice of oxidant

Carbamazepine (CBZ), which is one of the most commonly prescribed antiepileptic drugs and also used in the treatment of trigeminal neuralgia and psychiatric disorders, is metabolized primarily by the cytochromes P450. A homologous series of β-brominated porphyrins derived from 5,10,15,20-tetrakis(4-carbomethoxyphenyl)porphyrinatomanganese(III) chloride, i.e., Mn(III)(BrxTCMPP)Cl (x = 0, 2, 4, 6, and 8), was investigated as cytochrome P450 models for CBZ oxidation in CH2Cl2 by iodosylbenzene, iodobenzene diacetate, tert-butyl hydroperoxide, meta-chloroperoxybenzoic acid, and hydrogen peroxide. Unlike previous studies on metalloporphyrin-based CBZ oxidation, which yielded CBZ epoxide (CBZ-EP) as the sole product, the Mn(III)(BrxTCMPP)Cl systems catalyzed both the oxidation of CBZ to CBZ-EP and the formation of the respective vicinal diol, CBZ-DiOH. The influence of β-bromination of the macrocycle and the choice of the oxidant on the catalytic properties of the Mn(III)(BrxTCMPP)Cl (x = 0, 2, 4, 6, and 8) series were examined. Some partially β-brominated Mn-porphyrins surpass the corresponding octabrominated analogue in efficiency and selectivity, but the extent by which the β-bromination affects the catalytic activity depends on the choice of oxidant. The selectivity for CBZ oxidation to yield the respective epoxide reached 100% or ∼94% by using tert-butyl hydroperoxide or hydrogen peroxide as oxygen donors, respectively.

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► Mn-porphyrins can be used as cytochrome P450 models for carbamazepine oxidation.
► Extension of porphyrin β-bromination affects the catalytic outcome.
► 100% selectivity to the epoxide was achieved by using tert-butyl hydroperoxide.
► Mn-porphyrins are promising, bioinspired catalysts for the oxidation of drugs.