We developed syntheses of various polycyclic alkaloids, among them a highly enantioselective access to the phenanthroindolizidine (S)-Tylophorine which has been demonstrated to possess a wide range of biological activities. For instance, it has been shown to be a potent inhibitor of eukaryotic protein biosynthesis and to inhibit RNA-transcription as well as the action of several cyclins regulating the cell cycle.
For the preparation of the racemic alkaloid, a short synthesis based on the Stevens rearrangement of a nitrile-stabilized ammonium ylide has been developed. It comprises only five linear steps two or even three which can be performed in a one-pot procedure. Moreover, it requires no chromatographic purifications.
The chemistry of deprotonated α-aminonitriles in combination with Noyori`s asymmetric transfer hydrogenation allows the preparation of dimeric benzylisoquinolines such as tetramethylmagnolamine. In this case, the Ullmann diarylether synthesis was chosen to couple both benzylisoquinoline units.
For further information about our work on natural product synthesis please take a look at our list of publications.