Oxidation of 5 x 10(-3) M noradrenaline in aqueous phosphate buffer, pH 7.4, with K3Fe(CN)(6), NaIO4 or Fe2+/EDTA/H2O2 followed by extraction with ethyl acetate and acetylation with Ac2O/Pyr led to a main reaction product which was isolated and identified as 4-[bis-(1H-5,6-diacetoxyindol-2-yl)methyl]-1,2-diacetoxybenzene, an unprecedented [bis-(indol-2-yl)methyl] -benzene derivative unsubstituted on the 3-position of the indole rings. This product was also obtained in 40% yield by reaction of 5,6-dihydroxyindole with 3,4-dihydroxybenzaldehyde. Other components of the oxidation mixture were 1-acetyl-3,5,6-triacetoxyindole, derived from noradrenolutin, and 5,6-diacetoxyindole, originating from cyclisation/dehydration of the o-quinone of noradrenaline, along with some 3,4-diacetoxybenzaldehyde. Inspection of the aqueous phase revealed the presence of 3,4-dihydroxymandelic acid and 3,4-dihydroxybenzaldehyde, derived from oxidative breakdown of the 2-amino-1-hydroxyethyl chain via a p-quinomethane intermediate. These results disclose new aspects of the oxidative chemistry of noradrenaline beyond the aminochrome stage and provide a route to novel [bis-(indol-2-yl)methyl]-benzene derivatives of potential pharmacological interest. (c) 2005 Elsevier Ltd. All rights reserved.

New insight into the oxidative chemistry of noradrenaline: competitive o-quinone cyclisation and chain fission routes leading to an unusual 4-[bis-(1H-5,6-dihydroxyindol-2-yl)methyl]-1,2-dihydroxybenzene derivative / Manini, Paola; Pezzella, Alessandro; Panzella, Lucia; Napolitano, Alessandra; D'Ischia, Marco. - In: TETRAHEDRON. - ISSN 0040-4020. - STAMPA. - 61:16(2005), pp. 4075-4080. [10.1016/j.tet.2005.02.030]

New insight into the oxidative chemistry of noradrenaline: competitive o-quinone cyclisation and chain fission routes leading to an unusual 4-[bis-(1H-5,6-dihydroxyindol-2-yl)methyl]-1,2-dihydroxybenzene derivative.

MANINI, PAOLA;PEZZELLA, ALESSANDRO;PANZELLA, LUCIA;NAPOLITANO, ALESSANDRA;D'ISCHIA, MARCO
2005

Abstract

Oxidation of 5 x 10(-3) M noradrenaline in aqueous phosphate buffer, pH 7.4, with K3Fe(CN)(6), NaIO4 or Fe2+/EDTA/H2O2 followed by extraction with ethyl acetate and acetylation with Ac2O/Pyr led to a main reaction product which was isolated and identified as 4-[bis-(1H-5,6-diacetoxyindol-2-yl)methyl]-1,2-diacetoxybenzene, an unprecedented [bis-(indol-2-yl)methyl] -benzene derivative unsubstituted on the 3-position of the indole rings. This product was also obtained in 40% yield by reaction of 5,6-dihydroxyindole with 3,4-dihydroxybenzaldehyde. Other components of the oxidation mixture were 1-acetyl-3,5,6-triacetoxyindole, derived from noradrenolutin, and 5,6-diacetoxyindole, originating from cyclisation/dehydration of the o-quinone of noradrenaline, along with some 3,4-diacetoxybenzaldehyde. Inspection of the aqueous phase revealed the presence of 3,4-dihydroxymandelic acid and 3,4-dihydroxybenzaldehyde, derived from oxidative breakdown of the 2-amino-1-hydroxyethyl chain via a p-quinomethane intermediate. These results disclose new aspects of the oxidative chemistry of noradrenaline beyond the aminochrome stage and provide a route to novel [bis-(indol-2-yl)methyl]-benzene derivatives of potential pharmacological interest. (c) 2005 Elsevier Ltd. All rights reserved.
2005
New insight into the oxidative chemistry of noradrenaline: competitive o-quinone cyclisation and chain fission routes leading to an unusual 4-[bis-(1H-5,6-dihydroxyindol-2-yl)methyl]-1,2-dihydroxybenzene derivative / Manini, Paola; Pezzella, Alessandro; Panzella, Lucia; Napolitano, Alessandra; D'Ischia, Marco. - In: TETRAHEDRON. - ISSN 0040-4020. - STAMPA. - 61:16(2005), pp. 4075-4080. [10.1016/j.tet.2005.02.030]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/204345
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