Synthesis of M + 4 Stable Isotopomers of Ergometrine and Ergometrinine.

The priority ergot alkaloids ergometrine and ergometrinine are highly toxic mycotoxins naturally occurring in different types of grains (i.e. rye, wheat, rice), as well as grain-based foods and, therefore, have gained increasing importance for food safety over the last years. The application of HPLC-MS/MS for the analysis of ergot alkaloids in food presupposes the availability of isotopically labelled internal standards. Thus, a multistep synthesis was developed for ergometrine-(N-13CD3) and its epimer ergometrinine-(N-13CD3) with a mass shift of four units compared with the parent compounds. The synthesis is based on the preparation of stable isotope labelled lysergic acid that was coupled with (S)-alaninol. The chemical synthesis of both compounds has been achieved in six steps with an overall yield of 1 % (ergometrine-(N-13CD3)) and 0.6 % (ergometrinine-(N-13CD3)), respectively. Structural identification was performed by MS analysis as well as 1H and 13C NMR.