Total Synthesis of Clavicipitic Acid and Aurantioclavine: Stereochemistry of Clavicipitic Acid Revisited

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 R-f 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