The Chemistry and Biology of Isoquinoline Alkaloids

Stereochemical Factors and Receptor Interactions Associated with Narcotic Analgesics

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 Serturner. 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.

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

In the several years since Blaschko [1] first suggested that dopamine might be a neurotransmitter substance, many chemical compounds have been found to possess dopamine-like actions. This review surveys classes of structures for which putative dopaminergic agonism has been reported, and cites structure-activity correlations. Some aspects of metabolism of the agents are addressed, which seem to have relevance to structure-activity considerations and to strategy of drug design.

Dopamine agonists: structure-activity relationships

Die absolute Konfiguration der atropisomeren Diaryl‐Verbindungen

Thebaine (VII) has been degraded to (−)-cis-[2-methyl-2-carboxy-cyclohexyl-(1)]-acetic acid (III), thus providing experimental proof of the absolute configuration of morphine, thebaine and related alkaloids.

O. Jeger

Papers

Über die absolute Konfiguration des Morphins und verwandter Alkaloide