Synthetic studies aiming at the preparation of new pyridoindois of medicinal interest

• Grant number: 20/13962-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: February 01, 2021
• End date: October 21, 2025
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Giuliano Cesar Clososki
• Grantee: Thais Rodrigues Arroio
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 22/08837-6 - Synthesis of (Hetero)Arylsulfonamides via photocatalytic C-H-sulfamoylation using sulfamoyl radicals, BE.EP.DR

Abstract

N-hereterocycle compounds containing fused rings, such as pyrido [1,2-a] indoles, have been attracting interest from researchers due to the great pharmacological potential they present, being used as leishmanicidal, antiviral, anti-inflammatory, antibacterial and anti-tumor agents. On the other hand, many derivatives stand out for their luminescent properties, thus envisioning different technological applications. The scarcity of synthetic strategies in the literature that allow the preparation of pyrido [1,2-a] functionalized indoles inspired us for the main objective of this project, which consists in the development of new methodologies for the preparation of derivatives of interest to Medicinal Chemistry. For this, we will carry out a comprehensive study on the application of mixed Li/Mg and Li/Zn reagents in the regioselective metallation of N-heterocycle substrates containing the cyan group in its structure, which has great synthetic versatility. From organometallic intermediates, alcohols and functionalized aryl ketones can be obtained through reactions with aldehydes and ketones, respectively. These building blocks will be used in cyclization studies using different catalytic strategies, among which, modern photocatalysis techniques. The project should contribute to the synthesis of several pyridoindoles of unprecedented structure, some with a structure related to the alkaloid fascaplisine, a natural product with relevant antitumor activity. This and other compounds to be synthesized during the project will be sent to partner groups for biological evaluation. In addition, a partnership was established with the group of Prof. Dr. Georg Manolikakes, from Kaiserslautern University, Germany, for an internship, in order to complement the study of reactions involving photocatalysis and continuous flow. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BERTALLO, CAMILA R. S.; BERLIM, LEONARDO S.; OLIVIER, DANILO S.; ARROIO, THAIS R.; ITO, AMANDO S.; CLOSOSKI, GIULIANO C.. Synthesis and photophysical properties of 2-aryl-5-carbonyl indolizines. DYES AND PIGMENTS, v. 198, FEB 2022. (18/14150-8, 15/03007-1, 18/02855-7, 20/13962-9)

ARROIO, THAIS R.; BERTALLO, CAMILA R. S.; LEONELO, LAILA AP. D.; CAIRES, FRANCO J.; NAAL, ROSE M. Z. G.; CLOSOSKI, GIULIANO C.. Synthesis of novel π-extended 2,5-disubstituted indolizines and their absorption and fluorescence properties. Journal of Molecular Structure, v. 1315, p. 12-pg., 2024-06-17. (20/13962-9, 22/05327-7, 14/50867-3, 15/03007-1)

ARROIO, THAIS RODRIGUES; NAU, JAN PHILIPP; HOFMAN, KAMIL; FOERSTER, CHRISTOPH; FABER, STEPHANIE L.; BECKER, SABINE; HEINZE, KATJA; CLOSOSKI, GIULIANO CESAR; MANOLIKAKES, GEORG. Generation of Sulfamoyl Radicals via Visible-Light Mediated Fixation of Sulfur Dioxide for the Synthesis of Sulfonamides. ADVANCED SYNTHESIS & CATALYSIS, v. 367, n. 1, p. 6-pg., 2024-11-20. (20/13962-9, 22/08837-6)