Postulated Biosyntheses of the Physostigmine Ring System

In the original paper which presented Robinson s structure for physostigmine Stedman and Barger (13) suggested a possible biosynthetic route to the physostigmine ring system (see accompanying scheme). Tryptamine, produced by decarboxylation of tryptophan, was 

Julian and Pikl (38) have also proposed a route of biosynthesis of physostigmine. They considered that the essential steps involved first oxidation and then methylation of tryptophan to an oxindole LII which was reductively ring closed to the physostigmine ring system. It will be 

Witkop and Hill noted that there was some analogy for the C-methylation step to be found in the recently reported C-methylation of di-hydroberberine with formaldehyde (50). 

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