ISBN 9783843922296

978-3-8439-2229-6, Reihe Organische Chemie

Nils Marsch
Studies towards the synthesis of raputindole A, a dimeric indole alkaloid from the rutaceous tree Raputia simulans

191 Seiten, Dissertation Technische Universität Braunschweig (2015), Softcover, A5

Zusammenfassung / Abstract

In 2010, the raputindoles A-D were isolated from the rutaceous tree Raputia simulans Kallunki from tropical South America. These bisindoles bear a unique cyclopentene ring anellated to the 5,6-position of one of the indole core structures. This dissertation describes the development of a synthetic approach towards raputindole A, starting from a general precursor leading to small molecule building blocks and bisindole precursors. 6-Iodoindole was synthesized via Batcho-Leimgruber indole synthesis to serve as a precursor for Pd-mediated reactions. A variety of 6-substituted indoles has been synthesized and subjected to cytotoxicity tests. Two natural products from Monodora angolensis and Monodora tenuifolia showed the highest activity among the synthesized indoles. Propargyl alcohol indoles and bisindoles have been synthesized from both 6-iodoindole and a more advanced 5,6-functionalized indole. A Meyer-Schuster rearrangement was carried out on propargyl alcohols to yield alpha,beta-unsaturated ketones which were subjected to various conditions in order to achieve cyclization to the core structure of raputindole A. samarium diiodide induced dimerization of indoles with alpha,beta-unsaturated ketone substructures led to cyclopentyl bisindoles with an unusual stereochemistry. The natural product indiacen B from the myxobacterium Sandaracinus amylolyticus was synthesized. Indiacen B exhibits antimicrobial activity against Gram-positive and Gram-negative bacteria and the fungus Mucor hiemalis. A five step sequence yielded the natural product in 5% overall yield. The antimicrobial activity of the natural product against Nocardioides simplex, Mycobacterium diernhoferi, Chromobacterium violaceum and Mucor hiemalis was confirmed.