Iodo-funcionalização seletiva C3-H de 1H-indóis biocatalisada pelo sistema lacase-mediador redox

Abstract

1H-indole is a naturally occurring compound which has a bicyclic structure which consists of a benzene ring fused to a pyrrole ring. This compound is naturally produced by bacteria and fungi and is present in human feces, being one of the components responsible for the unpleasant odor. However, in low concentrations it has a floral odor, and therefore, it is used in the perfumery industry. 1H-indole is part of the chemical structure of important natural molecules with relevant biological activities, such as the amino acid tryptophan, the neurotransmitter serotonin and the hormone melatonin. Because it is widely found as part of the structure of natural products and with relevant biological activities, 1H-indole is considered a privileged structure, and therefore, a structure widely used in medicinal chemistry. Proof of this is the high number of drugs available for the treatment of diseases such as cancer, depression and hypertension. On the other hand, laccase enzymes have been highlighted as important biocatalysts in chemical reactions that are not natural to these enzymes, providing the development of synthetic methodologies that meet the principles of green chemistry. Thus, combining the importance of 1H-indole and its derivatives as intermediates in synthetic processes and the power of biocatalysis as a strategy for chemical transformation, this work aim to develop a biotechnological approach, using the laccase-redox mediator system, for iodine functionalization of 1H-indole and derivatives. The iodine-functionalized indole compounds at the C3 position are important intermediates, providing the obtaining of functionalized compounds, mainly from cross-coupling reactions. Trametes versicolor laccase and ABTS proved to be a suitable laccase-redox mediator system for the oxidation of the iodide anion, supplied in the form of potassium iodide, generating the reactive iodine species, I3 -. In turn, I3 - promotes iodine functionalization of 1H-indole with high selectivity at the C-3 position and an excellent yield of 99%. The methodology was extended to other sixteen derivatives of 1Hindole, in which convertion values above 97% and yields above 89% were also observed. Due to the high conversion values and the simplicity of the reaction medium, the methodology also stands out for the simplified isolation step of the products. Therefore, a methodology with a biotechnology approach was proposed and developed for the iodine functionalization of 1Hindoles with results comparable to the methodologies already described in the literature. However, with the benefits offered by biocatalysis. [resumo fornecido pelo autor]