A highly substrate specific enzyme has been discovered and purified to homogeneity, which transfers the acetyl-moiety from free coenzyme A to the 7-OH group of salutaridinol. The formed 7-O-acetyl-salutaridinol spontaneously closes the oxide bridge at pH 8-9 by allylic elimination furnishing the morphine precursor thebaine. The morphine skeleton consists of five ring systems housing five asymmetric centers. Thebaine is the first biogenetic precursor of morphine containing already this pentacyclic ring system. The immediate precursor of thebaine is the tetra-acyclic salutaridinol. The transition of salutaridinol to thebaine involves the closure of the oxide bridge between C-4 and C-5 of the biogenetic precursor (7S)-salutaridinol. Salutaridinol has the correct (7S)-configuration for an allylic syn-displacement of the activated hydroxyl group by the phenolic hydroxyl group which follows the precedented stereocontrol for SN2' substitutions at cyclohexene rings. The oxide bridge closure was first achieved in studies on the chemical synthesis of morphine by using dibrominated precursors. Later, with the biogenetic precursor, salutaridinol, in hand, it was shown, that under acid catalysis the pentacycle was easily formed both with the (7R)- and (7S)-epimer yielding in both cases thebaine (Fig. 1).