603. Alkaloid biosynthesis. Part VIII. Use of optically active precursors for investigation on the biosynthesis of morphine alkaloids

How human neuroblastoma cells make morphine

“…This inversion of configuration was most plausibly explained by the intermediate formation of the 1,2-dehydroreticulinium ion from (S)-reticuline, followed by stereospecific reduction to yield the desired (R)-configured enantiomer. This hypothesis was verified by feeding (22,23) and enzymatic (24,25) experiments with that quaternary alkaloid in poppy plants.…”

Endogenous formation of morphine in human cells

“…The degree of isotopic labeling was 24%. This experiment demonstrates that (S)-reticuline en route to morphine undergoes a change in configuration to (R)-reticuline as was observed and well studied in the poppy plant (15,(21)(22)(23)(24). Moreover, it suggests an intriguing biochemical analogy to the formation of this analgesic alkaloid in the plant kingdom.…”

“…One of the central questions in the biosynthesis of morphinan alkaloids in the opium poppy was the configuration at C-1 of the tetrahydrobenzylisoquinoline precursor molecules (21,22). Whereas in the poppy plant the firmly established precursors of the intermediate reticuline all have an (S) configuration at C-1, morphine and the morphinan precursors possess (R) configuration at the corresponding carbon atom C-9.…”

“…Whereas in the poppy plant the firmly established precursors of the intermediate reticuline all have an (S) configuration at C-1, morphine and the morphinan precursors possess (R) configuration at the corresponding carbon atom C-9. (S)-reticuline formed in the poppy plant is converted by means of 1,2-dehydroreticuline to (R)-reticuline, which in turn is then transformed into morphine (15,21,23,24). Therefore, it was necessary to determine the stereochemical configuration of reticuline produced by and accumulated in the human cell lines DAN-G and SH-SY5Y.…”

Presence and formation of codeine and morphine in the rat.

“…The identification by Hughes et al (1) of two endogenous opioid peptides, enkephalins, that interact with one of the many opioid receptors (8) has initiated a search for the endogenous ligands for the other opioid receptors. Chavkin et al (2) have proposed that another opioid peptide, dynorphin, could be the ligand for the K receptor.…”