Scalable total syntheses of (-)-hapalindole U and (+)-ambiguine H

The Stigonemataceae family of cyanobacteria produces, a class of biogenetically related indole natural products that include hapalindoles and ambiguines. In this full account, a practical route to the tetracyclic hapalindole family is presented by way of an eight-step, enantiospecific, protecting-group-free total synthesis of (-)-hapalindole U that features an oxidative indole-enolate coupling. With gram-scale access to hapalindole U, the first total synthesis of an ambiguine alkaloid, (+)-ambiguine H, was cornpleted via an isonitrile-assisted prenyfation of an indole followed by a photofragmentation cascade. (C) 2014 Elsevier Ltd. All rights reserved.