Preparation of Novel Unsymmetrical Bisindoles under Solvent-Free Conditions:  Synthesis, Crystal Structures, and Mechanistic Aspects

Abstract

Indole aziridines and their hydroxyl derivatives have been used for the preparation of a small library of novel functionalized bisindoles. Diversification of these building blocks by solvent-free C-C-bond formation on solid support yielded annulated Hymenialdisine analogues under mild reaction conditions. Indoles as C-nucleophiles form potentially pharmacologically active bisindoles through an electrophilic aromatic substitution pathway in good to excellent yields. Further transformations of the indole aziridines with H-, N-, and O-nucleophiles demonstrate their versatility as key intermediates in diversity oriented synthesis. The hydroxyl precursor leads also to unsymmetrical bisindoles under similar reaction conditions. Important intermediates and final library compounds were confirmed by X-ray analysis. Theoretical studies on these systems show the possible cationic intermediate in the substitution pathway.

Aziridine Ring Opening: An Overview of Sustainable Methods

“…developed a very efficient method for highly functionalized bis‐indoles 30 from aziridines 29 and various substituted indoles on activated silica under solvent‐free conditions (Scheme ) Authors reported that the arylation proceeded generally at the benzylic position of compound 29 in a highly regio and stereoselective manner and gave mainly trans products 30 . The activated silica as a solid support not only enhanced the regioselectivity of this reaction, but also helped to deprotect the two N ‐Boc groups …”

A Submarine Journey: The Pyrrole-Imidazole Alkaloids

“…Different series of HMD analogues were synthesized in order to establish a SAR [1,80,81]. In those derivatives, the main features that allow ( Z )-HMD to bind in the kinase ATP binding site were left unchanged, while attempts have been performed in order to improve selectivity and permeability [82–84]. …”

Katalytische Funktionalisierung von Indolen in einer neuen Dimension

“…Über eine neue Anwendung dieser Methode zur Konstruktion eines hochfunktionalisierten Polycyclus mit zwei Indolsystemen wurde von Tse und Mitarbeitern berichtet 129. In diesem Ansatz wurde die regioselektive Ringöffnung des N‐Arylsulfonamid‐substituierten Aziridins 108 in Benzylstellung durch aktiviertes Kieselgel unterstützt.…”