Synephrine, oxidation

Symphytine lb 188 Symphytine N-oxide lb 243 Synclisia alkaloids la 314 Synephrine lb 229... 

Recently adrenochrome has been obtained (as its semicarbazone) by the air oxidation of synephrine [i.e. /9-hydroxy-/J-(4-hydroxy-phenyl)ethylmethylamine (5)] in the presence of potato tyrosinase.46 This overall reaction must involve an initial hydroxylation of synephrine (5) to give adrenaline (2), which is subsequently oxidized to adrenochrome (1). 

Ephedrine, synephrine, and caffeine are all well absorbed from the gastrointestinal tract, hollowing ingestion of an oral dose, clinical effects are seen within 60 min and persist from 2 to 6 h. Ephedrine is metabolized in the liver by oxidative deamination, demethylation, aromatic hydroxylation, and... 

Suzuki O, Matsumoto T, Oya M, Katsumata Y. Oxidation of synephrine by type A and type B monoamine oxidase. Experientia 1979 35 1283-1284. 

Stohs, S., H.G. Preuss, and M. Shara. 2011. A review of the receptor-binding properties of p-synephrine as related to its pharmacological effects. Oxid. Med. Cell. Longev. voL 2011, doi 10.1155/2011/482973. 

Considering that, studies have been developed to establish the toxicological profile of p-synephrine. The acute administration of C. aurantium extract (2.5 % p-synephrine) and p-synephrine produced reduction in locomotor activity, gasping, exophthalmia, piloerection, and salivation, corroborating to the hypothesis that p-synephrine acts not only in p3-adrenoreceptors but also in other adrenergic receptors. However, all the effects were reversible and persisted for 3 h. The adrenergic stimulation alerts for the same possible side effects of p-synephrine and C. aurantium [78]. The subchronic toxicity of Citrus aurantium extract and p-synephrine were also determined and indicated a low subchronic toxicity in mice but a possible alteration in the oxidative metabolism [79]. 

On irradiation with ultraviolet light, tyrosine is readily converted to DOPA, which is then oxidised further, probably to dopachrome and then to melanin [29, 85-88]. Synephrine (41) behaves similarly, being oxidised first to adrenaline and then probably to adrenochrome which rearranges to adrenolutin [89]. These oxidations probably involved the initial formation of the semi-quinone followed by oxidation to the open-chain quinone [90]. Ultraviolet irradiation was also found to increase the rate of oxidation of tyrosine by tyrosinase in rat skin. OrrAo-quinones were produced in the reaction and it was concluded that the acceleration was due to the formation of low levels of these compounds from tyrosine [91]. 

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