Syntheses of the analgesic opium alkaloid morphine (1) and the antiviral, antileukemic Amaryllidaceae base pretazzetine (2) will be investigated. The focal reaction in both schemes is an intramolecular phenolic coupling. The blocked reticuline 24 serves as substrate for coupling in the morphine synthesis, whereas diaryloxazolidine 26 is to be oxidized in the approach to pretazzetine. Conversion of the bromosalutaridine 25 to 1 (Scheme 8) and of dienone 27 to 2 (Scheme 10) is patterned after established or presumed biosynthetic sequences. Reagents based on vanadium (plus 5) will be studied as oxidants for the phenolic couplings. The system VOF3-TFA-TFAA and a cyclodextrin-supported variant of the VOF3 oxidant are of primary interest. Enzyme mediated phenolic coupling of 24 and 26, using peroxidase and laccase enzymes, will also be investigated.
