The Biosynthesis of Tropane Alkaloids in Datura stramonium: The Identity of the Intermediates between N-Methylpyrrolinium Salt and Tropinone

Abstract

The biosynthesis of the tropane alkaloids in transformed root cultures of Datura stramonium has been studied using sodium [1,2-13C2]acetate, (R,S)-[2,3-13C2]-1-(1-methyl-2-pyrrolidinyl)propan-2-one {(R,S)-[2‘,3‘-13C2]hygrine}, ethyl (R,S)-[1,2-13C2,2-14C]-2-(1-methyl-2-pyrrolidinyl)acetate, and ethyl (R,S)-[2,3-13C2,3-14C]-4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoate. The incorporation of (R,S)-[2‘,3‘-13C2]hygrine into cuscohygrine and several other condensation products was high (15−40% specific incorporation), but label was not recovered in either tropine or tropine esters (hyoscyamine; 0.0 ± 0.5% specific incorporation). None of the recovered alkaloids was labeled when ethyl (R,S)-[1,2-13C2,2-14C]-2-(1-methyl-2-pyrrolidinyl)acetate was fed to the cultures. In contrast, sodium [1,2-13C2]acetate and ethyl (R,S)-[2,3-13C2,3-14C]-4-(1-methyl-2-pyrrolidinyl)-3-oxobutanoate were incorporated into hyoscyamine (9 and 2% specific incorporation, respectively) and a number of other tropane alkaloids (up to 12% spec...