Total syntheses of indolactam alkaloids (-)-indolactam V, (-)-pendolmycin, (-)-lyngbyatoxin A, and (-)-teleocidin A-2.
We report the total syntheses of (-)-indolactam V and the C7-substituted indolactam alkaloids (-)-pendolmycin, (-)-lyngbyatoxin A, and (-)-teleocidin A-2. The strategy for preparing indolactam V relies on a distortion-controlled indolyne functionalization reaction to establish the C4-N linkage, in addition to an intramolecular conjugate addition to build the conformationally-flexible nine-membered ring. The total synthesis of indolactam V then sets the stage for the divergent synthesis of the other targeted alkaloids. Specifically, late-stage sp2-sp3cross-couplings on an indolactam V derivative are used to introduce the key C7 substituents and the necessary quaternary carbons. These challenging couplings, in addition to other delicate manipulations, all proceed in the presence of a basic tertiary amine, an unprotected secondary amide, and an unprotected indole. Thus, our approach not only enables the enantiospecific total syntheses of four indolactam alkaloids, but also serves as a platform for probing complexity-generating and chemoselective transformations in the context of alkaloid total synthesis.
Department of Chemistry and Biochemistry, University of California, 607 Charles Young Drive East, Box 951569, Los Angeles, CA 90095, USA.
Noah F Fine
NF
Nathel
Department of Chemistry and Biochemistry, University of California, 607 Charles Young Drive East, Box 951569, Los Angeles, CA 90095, USA.
Tejas K
TK
Shah
Department of Chemistry and Biochemistry, University of California, 607 Charles Young Drive East, Box 951569, Los Angeles, CA 90095, USA.
Sarah M
SM
Bronner
Department of Chemistry and Biochemistry, University of California, 607 Charles Young Drive East, Box 951569, Los Angeles, CA 90095, USA.
Neil K
NK
Garg