Biosynthetic studies on the tropane alkaloid hyoscyamine in Datura stramonium; hyoscyamine is stable to in vivo oxidation and is not derived from littorine via a vicinal interchange process

Abstract

The conversion of littorine to hyoscyamine has been investigated by feeding deuterium labelled (RS)-[2-2H]-, [3, 3-2H2]-, [2, 3, 3-2H3]- phenyllactic acids to transformed root cultures of Datura stramonium. Isolation and GC–MS analyses of the isotope incorporation into the resultant hyoscyamine does not support the involvement of a vicinal interchange process operating during the isomerisation of littorine to hyoscyamine. Additionally a metabolism study with [1′-13C, 3′, 3′-2H2]-hyoscyamine has established that the alkaloid is metabolically stable at C-3′ with no evidence for a reversible in vivo oxidation process to the corresponding aldehyde. The data do not support an S-adenosy-l-methionine (SAM 5)/co-enzyme-B12 mediated process for the isomerisation of littorine to hyoscyamine.