The Chemistry of Hapalindoles, Fischerindoles, Ambiguines, and Welwitindolinones

Vikram Bhat, The University of Chicago
Apurva Dave, The University of Chicago
James A. MacKay, Elizabethtown College
Viresh H. Rawal, The University of Chicago


Isolated from diverse cyanobacteria, the hapalindole family of indole alkaloids comprises over 80 interrelated natural products. The family is further divided into several subclasses including the hapalindoles, fischerindoles, ambiguines, and welwitindolinones, each sharing one or more of the many common structural motifs, including an indole or oxindole core, a highly functionalized cyclohexane unit fused to the indole at C-3, and the uncommon isonitrile or isothiocyanate functionalities. Reported here is a comprehensive review covering the isolation of all currently known hapalindole-type alkaloids, the biological activity for several members of the family, and the proposed biosyntheses that give rise to the intricate structural diversity within the family. Finally, the major thrust of this chapter is a comprehensive outline of decades of cutting edge synthetic chemistry toward these complex alkaloids. To date, only a small fraction of the hapalindole-type alkaloids have yielded to chemical synthesis, yet the strategies and methodologies developed showcase the state of the art in synthetic chemistry and provide access to new compounds that can be evaluated for their biological activities. © 2014 Elsevier Inc.