Phenol oxidation and biosynthesis. Part XII. Stereochemical studies related to the biosynthesis of the morphine alkaloids

Abstract

Ozonolysis of tritiated salutaridinols-I and -II has afforded glyceric acids whose absolute configurations have been determined by the isotope dilution method. In this way the stereochemistry of salutaridinol-I, the precursor of the morphine alkaloids, has been defined unambiguously.

Oxidation of tritiated (+)- and (–)-reticuline, followed by isotope dilution analysis, has confirmed the configurational relationship between benzylisoquinoline and morphine alkaloids. The results obtained amount to a long sought total synthesis of morphine from reticuline following the biogenetic route.

The configurational relationship between morphine and benzylisoquinoline alkaloids has been further confirmed by the reduction of salutaridine to give, after appropriate methylation, (–)-laudanosine. The bond broken in this reduction is the bond formed in the biogenetic oxidative cyclisation of (–)-reticuline.