The Chemistry and Pharmacology of Morphinan Alkaloids

Abstract

The chemistry of morphinan drugs is closely related to that of morphine through recognition of its structure by Robinson and Sugasawa (1933) and Schopf and Thier-felder (1939). Real progress, however, was made when Grewe and Mondon (1948) reported a novel detailed synthesis of morphinan, the basic unit of the opium alka-loids. This accomplishment, together with the first total synthesis of morphine by Gates and Tschudi (1952), its biosynthesis from reticuline by Barton et al. (1965), the final proof of the stereochemistry of natural morphine proposed by Stork (1952) and Rapoport and Levine (1953) and confirmed by Kalvoda et al. (1955) and Goto's (1964) work on sinomenine, set the stage for an unprecedented effort by Universities , Pharmaceutical Industries and Government Research Laboratories (NllI), to synthesize structures simpler than that of morphine. It was hoped that total synthesis would afford compounds with similar biological features but devoid of unfavourable side-effects and without the addictive properties of morphine. It was expected that the accumulated knowledge would ultimately lead to a practical synthesis of morphine accomplished 30 years later by Rice at the NIH.