The Chemical History of Morphine: An 8000-year Journey, from Resin to de-novo Synthesis

Evidence of human use of opium dates back as far as the sixth millennium BCE. Ancient societies through the Renaissance period created a variety of opium products, proliferating its common use and subsequent addiction. Because the active moiety was not known at this time, the potency of these opium concoctions could neither be predicted nor controlled. The first step in identifying opium's active ingredient, morphine, was its chemical isolation in the early 1800s by Wilhelm Sertürner. The subsequent elucidation of morphine's chemical formula and Sir Robert Robinson's derivation of morphine's structural formula, which won him the 1947 Nobel Prize in Chemistry, round out 150 years of the incremental advances in our chemical understanding of morphine. Nevertheless, our attempts to synthesize morphine, despite our advanced knowledge in synthetic chemistry, are still no match for the plant-based extraction of morphine from the poppy plant. The status quo remains problematic socially, economically, and politically; the relationships between the countries laboriously growing poppy plants to extract morphine and those countries importing these painkillers are unstable at best. In this study, we contrast the cumulative scientific discoveries that have led to our current chemical knowledge of morphine with the centuries-old natural method of morphine production that still dominates the opioid market today.