Development of new routes for preparation of aryne precursors with application in stereoselective syntheses of bioactive alkaloids

• Grant number: 15/09984-9
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2015
• End date: June 30, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Cristiano Raminelli
• Grantee: Cristiano Raminelli
• Host Institution: Instituto de Ciências Ambientais, Químicas e Farmacêuticas (ICAQF). Universidade Federal de São Paulo (UNIFESP). Campus Diadema. Diadema , SP, Brazil

Abstract

The benzyne chemistry has found applications in organic chemistry, including total syntheses of natural products and preparations of functional materials. In this sense, 2-(trimethylsilyl)aryl trifluoromethanesulfonates appear as an important alternative for the formation of benzyne and derivatives, under mild reaction conditions, enlarging the scope of benzyne chemistry application in preparative organic chemistry. In this context, we intend to prepare iodinated silylaryl triflates, which will be subjected to the chemoselective Suzuki coupling, promoting the formation of silylbiaryl triflates. Simultaneously, we will produce functionalized silylaryl triflates through sequence of reactions that do not employ strongly basic/nucleophilic species, involving organometallic catalysis in one of the steps. In parallel, we will perform the stereoselective total syntheses of the isoquinoline alkaloids (S)-tetrahydropalmatine, (+)-corydaline, (S)-nuciferine and (+)-isothebaine, with pharmacological potential of interest, imploying 2-(trimethylsilyl)aryl triflates in the corresponding key steps, under mild reaction conditions. Additionally, key intermediates and final products of the total syntheses, presented in our research project, will be tested against leishmaniasis and will have its toxicities assessed in cells and animals, by collaboration with research group from Faculdade de Medicina of the Universidade de São Paulo. (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)

MOREIRA, BARBARA V.; MURACA, ANA CAROLINA A.; RAMINELLI, CRISTIANO. Synthesis of Silylbiaryl Triflates by Chemoselective Suzuki Reaction. SYNTHESIS-STUTTGART, v. 49, n. 5, p. 1093-1102, MAR 2017. (15/09984-9)

RODRIGUES, REBECA ROCHA; RAMINELLI, CRISTIANO; PERES, LAURA OLIVEIRA. A mild and efficient method to prepare oligophenylenes (PPPs). EUROPEAN POLYMER JOURNAL, v. 106, p. 202-205, SEP 2018. (15/09984-9)

MURACA, ANA CAROLINA A.; PERECIM, GIVAGO P.; RODRIGUES, ALESSANDRO; RAMINELLI, CRISTIANO. Convergent Total Synthesis of (+/-)-Apomorphine via Benzyne Chemistry: Insights into the Mechanisms Involved in the Key Step. SYNTHESIS-STUTTGART, v. 49, n. 16, p. 3546-3557, AUG 2017. (15/09984-9)