Synthesis of Ergot Alkaloids from Tryptophan

[pHarmacist]

J. Am. Chem. Soc.; 1984; 106(6); 1813-1819

J. Rebek, Jr.,* D. F. Tai, and Y.-K. Shue

Contribution from the Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260. Received September 19, 1983

Abstract: The first total syntheses of lysergine and setoclavine are described, as well as a new and efficient synthesis of lysergic acid. The starting material for these syntheses is tryptophan, protected as its dihydro, dibenzoyl derivative. This material is dehydrated to the corresponding azlactone, which undergoes stereoselective intramolecular Friedel-Crafts acylation to give a tricyclic ketone intermediate. Reformatsky reaction with ethyl a-(bromomethy1)acrylate introduces the remaining four carbons and leads to a spiro methylene lactone that represents the branching point of the three syntheses. The high selectivity of the reactions described permits the synthesis of optically active ergot alkaloids from L-tryptophan.

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