First synthesis of important secondary oxidative metabolites of morphine and codeine with the Michael addition

Abstract: Morphine ( © Versita Sp. z o.o. Keywords: Morphine • Codeine • Metabolite • Glutathione • Cysteine 1 Department of Organic Chemistry, University of Debrecen, H-4032 Debrecen, Hungary 2 Department of Pharmaceutical Chemistry, Medical and Health Science Center, University of Debrecen, H-4032 Debrecen, Hungary Sandor Garadnay 1# , Zsuzsanna Gyulai 1 , Sandor Makleit 1† , Attila Sipos 2* Research Article 1 ) and codeine ( 2 ) are two representatives of medically important, frequently used natural opiates, therefore the exploration of their metabolic pathways and the exact characterization of the metabolites are main targets of their pharmacological studies. These morphinans also play a crucial role in drug abuse; therefore, the analysis and preparation of the metabolites for identification and quantitation in human samples are considered important aims. In order to allow the in-depth analysis of metabolites derived from the oxidative pathways through morphinone ( 3 ) and codeinone (