A Bioinspired Synthesis of Polyfunctional Indoles

Abstract

Polyfunctional indoles bearing substituents at C5 and C6 are prevalent in natural products, pharmaceuticals, agrochemicals, and materials. Owing to the remoteness of the C5 and C6 positions, indoles of this family can be difficult to prepare, and often require multistep syntheses. Herein, we describe a concise process that converts simple derivatives of tyrosine into 5,6-difunctionalized indoles by direct oxidation of C-H, N-H, and O-H bonds. Our work draws inspiration from the biosynthetic polymerization of tyrosine to make melanin pigments, but makes an important departure to provide well-defined indole heterocycles.

Chromene- and Quinoline-3-Carbaldehydes: Useful Intermediates in the Synthesis of Heterocyclic Scaffolds

“…Antitumoral [ 21 , 22 ], anti-arrhythmic [ 19 ], anti-inflammatory [ 23 ], antimicrobial [ 24 ], and antihypertensive properties are amongst the reported biological activities. The synthesis of indole derivatives is largely explored due to relevant biological applications described for this scaffold, and there are reports on the synthesis of indole hybrids [ 25 , 26 , 27 ]. We thought it would be interesting to obtain chromene-indole hybrids, so we studied the reaction of 2-aryl-4-chloro-2 H -chromene-3-carbaldehydes 2a – c with indole ( 3 ).…”

Biological activity and synthesis of 5,6-dihydroxyindole-2-carboxylic acid – biosynthetic precursor of melanins (microreview)

“…The protective methyl groups are removed with BBr 3 . 13 DHICA synthesis methods (continued) For the synthesis of DHICA, the authors 14 used a route involving the CuI-catalyzed coupling of 2-bromo-4,5-dimethoxybenzaldehyde (2) with ethyl isocyanoacetate which was followed by cyclization leading to an ester of 5,6-dimethoxyindole-2-carboxylic acid. Hydrolysis of the ester group and demethylation using BBr 3 afforded the target compound.…”

CSC and CIC Awards 2019

“…By combining bio‐inspired design with expertise in transition‐metal catalysis and aerobic oxidation, they develop solutions for the preparation of small molecules and macromolecules with important functions. They have reported on a bioinspired synthesis of polyfunctional indoles in a Communication in Angewandte Chemie …”