This research is directed to (1) the biosynthesis of the opium alkaloid, (2) modified opiate structures with enhanced agonist and antagonist activity, and (3) a practical total synthesis of thebaine and codeine. The biosynthetic work will focus on the enzymic conversion of reticuline to salutaridine and the metabolic fate of morphine in the plant. The modified opiate structures will be derived from etorphine and be elaborated with conformationally rigid nitrogen substituents. The total synthesis will emphasize economy of steps and control of asymmetry.