Picrotoxin synthesis

The possible therapeutic use of corianin (21) in the treatment of schizophrenia and the general influence of picrotoxanes on the central nervous system make more economic pathways desirable. Trost and Krische have shown that relais substance 431 can be easily prepared from commercially available picrotoxin 131). This constimtes a partial synthesis of corianin (21) in nine steps (Scheme 51). 

By relating ACh release and reduction in content following inhibition of ACh synthesis by hemicholinium-3 it could be shown that about one-third of the ACh released appears in the collection fluid held in the Perspex cylinder. This allowed the calculation of the turnover rate of cortical ACh when both content and release were measured. Table I shows ACh turnover rates calculated from these experiments. These rates are much slower than those calculated by Schuberth et al. (1970) from results based on the incorporation of labelled choline into ACh stores. However, because of some uncertainty about the size of the choline pool which is the precursor of ACh, their values cannot be considered definitive. It can be seen that although atropine in small doses does not decrease ACh content, it increases ACh turnover, and especially enhances the effect of a stimulant such as picrotoxin, on ACh turnover rate. 

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