A Short Synthesis of <i>Ergot</i> Alkaloids and Evaluation of the 5-HT<sub>1/2</sub> Receptor Selectivity of Lysergols and Isolysergols.
Nikhil R TaskerPeter WipfPublished in: Organic letters (2022)
Key transformations in a four-step synthesis of the <i>ergot</i> alkaloid scaffold include a novel cesium carbonate-mediated hydrogen autotransfer alkylation to generate the C(3)-C(4) bond and an intramolecular Heck reaction that directly establishes the C(9)-C(10) alkene of methyl lysergate. An ester reduction and a streamlined experimental procedure establish a readily scalable, expedient total synthesis of all four stereoisomers of lysergol and isolysergol, including the previously unknown (-)-lysergol, for pharmacological evaluation at 5-HT<sub>1A</sub> and 5HT<sub>2A,B,C</sub> receptors. A bicyclic scaffold is also characterized for the first time in the intramolecular Heck coupling.