Issue Date: March 31, 2014
A Practical Path To Morphine Alkaloids
Morphine is an indispensable narcotic drug derived from the opium poppy that has been used for centuries to relieve intense pain. The compound also serves as a precursor to a stable of other useful narcotics, such as codeine and hydromorphone. But chemists have struggled to devise a reasonably short synthetic pathway that can be used to produce morphine on an economically viable commercial scale. Building on decades of research by multiple groups, Vimal Varghese and Tomas Hudlicky of Brock University, in St. Catharines, Ontario, have devised a short chemoenzymatic total synthesis of ent-hydromorphone as an advanced model for making morphine (Angew. Chem. Int. Ed. 2014, DOI: 10.1002/anie.201400286). The new route effectively provides access to most opium-derived narcotics, the researchers note. Key features of the synthesis include coupling two building blocks via a Mitsunobu reaction to form a primary intermediate and the first use of an intramolecular Diels-Alder [4 + 2] cycloaddition to close the B ring in a morphine alkaloid synthesis. The total synthesis takes only 12 steps from scratch, or just seven steps from the primary intermediate, making it one of the shortest on record for morphine alkaloids.
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