Recent progress in chemoenzymatic synthesis of natural and unnatural products: Amaryllidaceae and
morphine alkaloids, opiate-derived pharmaceutical agents, and other targets of interest.


Prof. Tomas Hudlicky, Brock University, Canada


Abstract:

This lecture will provide an update on our efforts aimed at the synthesis of morphinans and their
derivatives of commercial value. The academic efforts originate with the enzymatic dihydroxylation
of aromatic substrates and aim at efficient syntheses of morphine and congeners. The industrial
process development relies on transition metal-catalyzed oxidative demethylation of thebaine and
oripavine and further conversion to naltrexone, naloxone, and other agents. N-Demethylation of
morphine alkaloids by fungal cytochromes is also being studied and compared with chemical processes
for overall efficiency.

In the Amaryllidaceae alkaloids area new derivatives of pancratistatin and narciclasine are being
synthesized and evaluated for activity in several cancer cell lines. Other targets of interest
include the synthesis of highly oxygenated compounds from the ipso-diol derived enzymatically from
benzoic acids.