Base-Mediated Nitrophenyl Reductive Cyclization for the Synthesis of Hexahydro-2,6-methano-1-benzazocines
Laura G Rodríguez1, Ana Delgado2, Carlos J Ciudad2
1Laboratori de Química Orgànica, Facultat de Farmàcia, IBUB, Universitat de Barcelona, Avenida Joan XXIII 27-31, 08028 Barcelona, Spain.
Abstract:
A Diels-Alder reaction leading to 4-nitrophenylcyclohexanones followed by a newly developed base-mediated reductive cyclization of the resulting ketone tethered to the nitrobenzene moiety gives access to the hexahydro-2,6-methano-1-benzazocine ring system present in several biologically interesting natural products such as aspernomine. The scope of the reaction was explored with eight substituted nitrobenzenes, obtaining yields of up to 87%. The highest cytotoxicity was observed in benzazocine 4h, bearing an enone moiety, which was active against eight cancer cell lines.
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