Isolation and Production of Morphinan Alkaloids and Their Conversion to Pharmaceuticals: From the Kabay-Process to Radiolabeled Opiates for Molecular Imaging

In 1925 János Kabay made the era-defining announcement of a new industrial procedure for the isolation of morphine alkaloids, followed two years later by his founding of the Alkaloida Chemical Company (Alkaloida Vegyészeti Gyár) in the North-East-Hungarian village of Bűdszentmihály. Kabay’s life achievements obtained official recognition in 2015 as a «Hungarikum», thus entering the national repository of matters of unique cultural value. In this survey we give an overview on the historical background of morphine alkaloid chemistry, its contemporary echoes, and the lasting consequences of the emergence of the Hungarian morphine alkaloid industry. Kabay’s innovation enabled the direct extraction of morphine from the poppy plant on an industrial scale, without resorting to the collection of opium, which has historically been a key aspect of the illegal narcotic trade, drug dependency, and opioid use disorder. By the 1950s, Alkaloida had evolved into one of the world’s most important producers of morphine and codeine. In addition to this historical narration, we also provide an overview of the chemical transformations of morphinan alkaloids to other active pharmaceutical ingredients, and present numerous examples for their pharmacological and pharmaceutical/medicinal applications. In the final part of our review, we present the syntheses of the most frequently used radiolabeled morphinans, and their applications for binding studies of opioid receptors in vitro and for molecular imaging by positron emission tomography.