clavicipitic-acid and indole

A new and short synthesis of racemic cis-clavicipitic acid was achieved by taking advantage of the double nucleophilic character of indole-4-pinacolboronic ester. Key to the success of the synthesis were an efficient and selective C-3 indole Friedel-Crafts alkylation and the development of an unprecedented intramolecular rhodium-catalyzed 1,2-addition of an aryl pinacolboronic ester to an unactivated imine.

Topics: Alkylation; Boronic Acids; Catalysis; Ergot Alkaloids; Esters; Imines; Indoles; Molecular Structure; Rhodium; Stereoisomerism

The stereocontrolled total synthesis of clavicipitic acid and aurantioclavine from a common azepino[5,4,3-cd]-indole intermediate is reported. This key azepinoindole nucleus was constructed via a one-pot Heck/Boc-deprotection/aminocyclization process from the 4-iodotryptophan derivative, which was assembled by a Pd-catalyzed indole synthesis procedure. After two or three additional deprotection steps from the azepinoindole intermediates, (-)-trans- and (-)-cis-clavicipitic acid were prepared. The syntheses of both (-)- and (+)-aurantioclavine were achieved with the same azepinoindole intermediates utilizing the Barton decarboxylation reaction as the key step to remove the stereohindered carboxylic acid. During the course of our synthesis, mis-assigned configurations of the synthesized clavicipitic acids and their derivatives in the literature were identified. Extensive studies including 2D-NMR study, X-ray diffraction analysis, titration experiment, and Rf value comparison unambiguously confirmed the new configuration assignment. The trans and cis configuration assignments of the synthesized clavicipitic acids and their derivatives in the past literature should be switched.

Topics: Catalysis; Ergot Alkaloids; Indoles; Magnetic Resonance Spectroscopy; Molecular Structure; Stereoisomerism; X-Ray Diffraction