| The Stigonemataceae family of cyanobacteria produces a class of over 60 biogenetically related, architecturally complex, topologically unique, and functionally rich indole natural products that form the basis of the hapalindole, fisherindole, ambiguine, and welwitindolinone indole alkaloids. Possessing a broad range of biological activity---including antifungal, antibacterial, and anticancer properties---such targets have served to stimulate the synthetic chemist for over a decade. Herein a practical and gram-scale route to the tetracyclic hapalindole alkaloid family is presented by way of an eight-step, enantiospecific, protecting group free total synthesis of (--)-hapalindole U. With gram scale access to hapalindole U, the first total synthesis of an ambiguine alkaloid, namely (+)-ambiguine H was completed. This work was made possible through several recently discovered and powerful methodologies including: (I) The first example of an oxidative coupling of a ketone with a brominated arene. (II) A powerful reductive Heck-type cyclization to forge the tetracyclic core. (III) A novel, isonitrile-assisted prenylation of an indole. (IV) A novel photofragmenation cascade to form an indole.;In 1987 Ando and co-workers isolated the unusual diterpene vinigrol from the fungal strain Virgaria nigra F-5408. The promising biological profile of vinigrol has attracted significant attention from the synthetic community. Herein we describe a simple and efficient synthetic route to the unusual decahydro-1,5-butanonaphthalene ring system found in vinigrol. In addition, synthetic routes are described to several advanced intermediates containing the entire carbon skeleton and full stereogenicity of this intriguing natural product. |
