Morphine (1) is a fascinating compound that has been used as an efficient analgesic and is indispensable in treating pains associated with cancer. However, morphine is strictly controlled by authorities due to its addictive nature. On the other hand, the structure of morphine is quite attractive from a synthetic point of view. Its complicated pentacyclic skeleton, including a quaternary carbon center, has stimulated extensive synthetic efforts. Hence, a number of synthetic studies and the total syntheses of morphine have been reported to date. In an effort to develop a novel morphine-type drug that is not addictive, we initiated our own studies of an efficient total synthesis of morphine.
Herein, we disclose a total synthesis of (−)-morphine which involves a construction of the morphinan skeleton using intramolecular aldol reaction and Michael reaction.