The formal synthesis of (-)-morphine is described. The C-ring in morphine was prepared in an optically pure form from d-glucal using Ferrier's carbocyclization reaction, and the vicinal tertiary and quaternary stereocenters in the C-ring were stereoselectively generated in a one-step reaction based on the cascade sequential Claisen rearrangement of an allylic vicinal diol derivative. After the one-step formation of the dibenzofuran structure, the intramolecular Friedel-Crafts type reaction effectively constructed the ABCE-phenanthrofuran skeleton. Introduction of a tosylamide function, followed by reductive cyclization furnished (-)-dihydroisocodeine, the known synthetic intermediate for (-)-morphine.
- Cascade Claisen rearrangement
- Friedel-Crafts type cyclization
- Total synthesis
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry