Total synthesis of morphine and related alkaloids

Synthesis of morphine-like alkaloids in chemistry describes the total synthesis of the natural morphinan class of alkaloids that includes codeine, morphine, oripavine, and thebaine and the closely related semisynthetic analogs methorphan, buprenorphine, hydromorphone, hydrocodone, isocodeine, naltrexone, nalbuphine, oxymorphone, oxycodone, and naloxone.

This "dissonant connectivity" makes bond formation more difficult and therefore significantly complicates any synthetic strategy that is applied to this family of molecules.

The hydrocodone synthesis of Kenner C. Rice is one of the most efficient and proceeds in 30% overall yield in 14 steps.

[5] Several other syntheses were reported, notably by the research groups of Evans,[6] Fuchs,[7] Parker,[8] Overman,[9] Mulzer-Trauner,[10] White,[11] Taber,[12] Trost,[13] Fukuyama,[14] Guillou,[15] Stork,[16] Magnus,[17] Smith,[18] and Barriault.

The Rice synthesis follows a biomimetic route and is the most efficient reported to date.