Thebaine after vinylether cleavage yields neopinone which exis& in a chemical equilibrium with codernone. It is demanstmted that cc&ii: NADP oxidoreductase in the presence of NAUPH shifts this equilibrium quantitatively towards codeine. The opium poppy, Papaver somniferum, is unique in its ability to cleave the enolic ether in the thebaine molecule yielding neopinone.14 In an elegant set of experiments it was shown that this methyl cleavage occurs with retention of the 6-oxygen atom. 4 Neopinone has been demonstrated to be a natural constituent of P. somniferuml and is known to rearrange into codeinonez in aqueous solution. It was assumed that this marrangement could also occur in the P. somnifenun plant in vivo.1 The stereoselective reduction of codeinone to codeine was observed to take place in cNde extracts of the poppy plant or cell culture in the presence of NADH as a reductant.5-7 An obviously different enzyme has now been purified to homogeneity from P. somniferum cell cultures and differentiated poppy plants and shown to be absolutely specific for NADPH and codeinonelcodeine as well as a few analogues (Lenz and Zenk. manuscript in preparation). This highly substrate specific and stereoselective enzyme was named codeine: NADP oxidoreductase. This part of the morphine biosynthetic pathway leads from thebaine via nwpinone and codeinone to codeine, which is one of the most effective and widely used analgesic and antitussive agents. tJ.4 However, until now, no enzymic analysis has been conducted to demonstrate whether the predicted transformation of neopinone to codeinone occurs spontaneously or whether it is enzyme catalyzed.