Eastern Kentucky University
Intermediate Steps Towards the Total Synthesis of Ergovaline
Institution
Eastern Kentucky University
Faculty Advisor/ Mentor
Darrin Smith; Joseph Bequette
Abstract
Ergovaline is an ergot alkaloid isolated from tall fescue grasses infested with the fungus Neotyphodium lolii. It poses a significant threat to the health of forage animals (especially cattle and horses in Kentucky) since it can produce a toxicosis in these animals. Research with this biologically active molecule and its effect on forage animals is currently growing, but the availability of the molecules, as standard material, is limited and hinders research efforts. Generating a synthetic route towards ergovaline is a more economically attractive and time saving option when compared to recoveries after arduous extraction from plants. Research involved a subset of reactions to synthesize this natural product involved with the toxicosis. Specifically, synthesis of the key intermediates, cyclo(L-pro-L-val) and (S)-ethyl benzyloxymethyl malonate acyl chloride, is described. The cyclo(L-pro-L-val) was derived from the conveniently available starting materials L-Valine and L-Proline with direct addition of valine ethyl ester to Cbz-proline, which proceeded under an inert atmosphere. For the other intermediate, a key feature of the synthesis is the chiral resolution of the (R)-enantiomer of ethyl benzyloxy-methyl malonate by crystallization using the resolving agent (S)-alpha-methylbenzylamine. Structural analysis using infrared (IR) spectroscopy, nuclear magnetic resonance (NMR), and mass spectrometry (MS) was conducted.
Intermediate Steps Towards the Total Synthesis of Ergovaline
Ergovaline is an ergot alkaloid isolated from tall fescue grasses infested with the fungus Neotyphodium lolii. It poses a significant threat to the health of forage animals (especially cattle and horses in Kentucky) since it can produce a toxicosis in these animals. Research with this biologically active molecule and its effect on forage animals is currently growing, but the availability of the molecules, as standard material, is limited and hinders research efforts. Generating a synthetic route towards ergovaline is a more economically attractive and time saving option when compared to recoveries after arduous extraction from plants. Research involved a subset of reactions to synthesize this natural product involved with the toxicosis. Specifically, synthesis of the key intermediates, cyclo(L-pro-L-val) and (S)-ethyl benzyloxymethyl malonate acyl chloride, is described. The cyclo(L-pro-L-val) was derived from the conveniently available starting materials L-Valine and L-Proline with direct addition of valine ethyl ester to Cbz-proline, which proceeded under an inert atmosphere. For the other intermediate, a key feature of the synthesis is the chiral resolution of the (R)-enantiomer of ethyl benzyloxy-methyl malonate by crystallization using the resolving agent (S)-alpha-methylbenzylamine. Structural analysis using infrared (IR) spectroscopy, nuclear magnetic resonance (NMR), and mass spectrometry (MS) was conducted.