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Development of methodologies and synthetic processes employing a new technological platform: micro and meso reactor assisted synthesis of natural products and derivatives with potential pharmacological activity

Grant number: 14/26378-2
Support type:Research Grants - Young Investigators Grants
Duration: August 01, 2015 - July 31, 2020
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Júlio Cezar Pastre
Grantee:Júlio Cezar Pastre
Home Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated grant(s):18/14555-8 - Chemical reactions under continuous flow conditions: chemical and economic aspects of the use of enabling technologies for obtaining low cost medicines, AV.EXT
Associated scholarship(s):18/25233-1 - Continuous flow synthesis of biomass-derivatives, BP.MS
18/09861-2 - Synthesis of novel ionic liquids from renewable sources and application on biomass conversion, BP.DR
17/24294-4 - Total synthesis and evaluation of the cytotoxicity of cyclic depsipeptides Kohamamides A, B and C, BP.IC
17/19953-9 - Total synthesis and evaluation of the cytotoxic activity of cacofurans A and B, BP.IC
15/18572-6 - Continuous flow synthesis of 3-thio-1,2,4-triazoles and biological evaluation, BP.DR

Abstract

The fine chemicals industry is entirely based on batch processes. Although the performance of batch reactors is well predictable, there are some limitations related to scale-up, reproducibility, safety, etc. The use of continuous processes by the fine chemicals industry is hampered mainly by financial and regulatory issues, however the high competitiveness of the industry and the pressure for a more sustainable manufacturing should boost a change of this paradigm. In this context, the use of continuous micro- and meso-reactors in the early stages of development stands as a promising alternative. Indeed, micro- and meso-reactors technology has been employed in the multi-step synthesis of molecules with high added value, particularly in academia. Micro- and meso-reactors offer significant advantages over traditional batch reactors such as faster and safer reactions, purer products, fast reaction optimization, easer scale up and integration of processes that are usually performed separately such as synthesis, purification and analysis. In this context, this proposal has as the main goal the establishment of a research group in the field of micro-reactor assisted organic synthesis. To achieve this goal, we intend to develop efficient methods for synthesis using micro and meso-reactors, aiming at the preparation of compounds with different properties and applications, such as natural products, drugs and new drug candidates. This proposal is strategically divided into sub projects that envolves (i) the development of new procedures for conjugate addition reactions and copper catalyzed allylic substitution reactions in continuous flow conditions, (ii) the synthesis of carbon nanotube supported organocatalyst aiming at its application to the addition of organozinc reagents to aldehydes and other organocatalyzed reactions, (iii) the development of methodologies for the ketene generation under continuous flow conditions and its application for multi step synthesis and (iv) the synthesis of biologically active natural products, such as goniothalamin, spilanthol, piplartine, cenocladamide and derivatives, using this platform for their preparation, aiming at surpassing limitations associated with the batch mode providing an alternative route. Also, this proposal aims to support further studies for the evaluation of the biological activity of the compounds prepared through the established collaborations with researchers from CPQBA / UNICAMP. (AU)

Scientific publications (13)
(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)
GALAVERNA, RENAN; MCBRIDE, TOM; PASTRE, JULIO C.; BROWNE, DUNCAN L. Exploring the generation and use of acylketenes with continuous flow processes. REACTION CHEMISTRY & ENGINEERING, v. 4, n. 9, p. 1559-1564, SEP 1 2019. Web of Science Citations: 0.
GALAVERNA, RENAN; FERNANDES, LUCAS P.; BROWNE, DUNCAN L.; PASTRE, JULIO C. Continuous flow processing as a tool for the generation of terpene-derived monomer libraries. REACTION CHEMISTRY & ENGINEERING, v. 4, n. 2, p. 362-367, FEB 1 2019. Web of Science Citations: 2.
ALONSO, ISABELLA G.; YAMANE, LAIS T.; DE FREITAS-BLANCO, VERONICA S.; NOVAES, LUIZ F. T.; FRANZ-MONTAN, MICHELLE; DE PAULA, ENEIDA; RODRIGUES, MARILI V. N.; RODRIGUES, RODNEY A. F.; PASTRE, JULIO C. A new approach for the total synthesis of spilanthol and analogue with improved anesthetic activity. Tetrahedron, v. 74, n. 38, p. 5192-5199, SEP 20 2018. Web of Science Citations: 0.
GALAVERNA, RENAN; RIBESSI, RAFAEL L.; ROHWEDDER, JARBAS J. R.; PASTRE, JULIO C. Coupling Continuous Flow Microreactors to MicroNIR Spectroscopy: Ultracompact Device for Facile In-Line Reaction Monitoring. ORGANIC PROCESS RESEARCH & DEVELOPMENT, v. 22, n. 7, p. 780-788, JUL 2018. Web of Science Citations: 2.
FORNI, JOSE AUGUSTO; TONETO NOVAES, LUIZ FERNANDO; GALAVERNA, RENAN; PASTRE, JULIO C. Novel polystyrene-immobilized chiral amino alcohols as heterogeneous ligands for the enantioselective arylation of aldehydes in batch and continuous flow regime. CATALYSIS TODAY, v. 308, n. SI, p. 86-93, JUN 15 2018. Web of Science Citations: 0.
NOVAES, LUIZ F. T.; GONCALVES, KALIANDRA DE ALMEIDA; TRIVELLA, DANIELA B. B.; PASTRE, JULIO C. Formal Total Synthesis of Actinoranone: Synthesis Approaches and Cytotoxic Studies. Journal of Organic Chemistry, v. 83, n. 9, p. 5160-5176, MAY 4 2018. Web of Science Citations: 3.
GALAVERNA, RENAN; BREITKREITZ, MARCIA C.; PASTRE, JULIO C. Conversion of D-Fructose to 5-(Hydroxymethyl)furfural: Evaluating Batch and Continuous Flow Conditions by Design of Experiments and In-Line FTIR Monitoring. ACS SUSTAINABLE CHEMISTRY & ENGINEERING, v. 6, n. 3, p. 4220-4230, MAR 2018. Web of Science Citations: 12.
DE SOUZA, JULIANA M.; GALAVERNA, RENAN; DE SOUZA, ALINE A. N.; BROCKSOM, TIMOTHY J.; PASTRE, JULIO C.; DE SOUZA, RODRIGO O. M. A.; DE OLIVEIRA, KLEBER T. Impact of continuous flow chemistry in the synthesis of natural products and active pharmaceutical ingredients. Anais da Academia Brasileira de Ciências, v. 90, n. 2, p. 1131-1174, 2018. Web of Science Citations: 8.
JULIANA M. DE SOUZA; RENAN GALAVERNA; ALINE A.N. DE SOUZA; TIMOTHY J. BROCKSOM; JULIO C. PASTRE; RODRIGO O.M.A. DE SOUZA; KLEBER T. DE OLIVEIRA. Impact of continuous flow chemistry in the synthesis of natural products and active pharmaceutical ingredients. Anais da Academia Brasileira de Ciências, v. 90, n. 1, p. -, 2018.
DAMIAO, MARIANA C. F. C. B.; GALAVERNA, RENAN; KOZIKOWSKI, ALAN P.; EUBANKS, JAMES; PASTRE, JULIO C. Telescoped continuous flow generation of a library of highly substituted 3-thio-1,2,4-triazoles. REACTION CHEMISTRY & ENGINEERING, v. 2, n. 6, p. 896-907, DEC 2017. Web of Science Citations: 3.
NOVAES, LUIZ F. T.; PASTRE, JULIO C. Formal Total Synthesis of Actinoranone and Asymmetric Synthesis of Labda-7,13-(E)-dien-15-ol. ORGANIC LETTERS, v. 19, n. 12, p. 3163-3166, JUN 16 2017. Web of Science Citations: 4.
SANTOS, CARLA C. F.; PARADELA, LUCIANA S.; NOVAES, LUIZ F. T.; DIAS, SANDRA M. G.; PASTRE, JULIO C. Design and synthesis of cenocladamide analogues and their evaluation against breast cancer cell lines. MedChemComm, v. 8, n. 4, p. 755-766, APR 1 2017. Web of Science Citations: 5.
LUIZ F. T. NOVAES; JULIO C. PASTRE. AVANÇOS RECENTES NA HIDROAMINAÇÃO DE COMPOSTOS INSATURADOS. Química Nova, v. 40, n. 8, p. -, Set. 2017.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.
Filed patent(s) as a result of this research project

PROCESSO DE OBTENÇÃO DO ESPILANTOL E ANÁLOGOS, ESPILANTOL E ANÁLOGOS OBTIDOS BR1020160178711 - Universidade Estadual de Campinas (UNICAMP) . Júlio Cezar Pastre ; Isabella Gonçalves Alonso - July 2016, 29

PROCESSO DE OBTENÇÃO DO ESPILANTOL E ANÁLOGOS, ESPILANTOL E ANÁLOGOS OBTIDOS PCT/BR2017/000085 - Padtec S/A ; Universidade Estadual de Campinas (UNICAMP) . Julio Cezar Pastre ; Isabella Gonçalves Alonso - July 2017, 28

COMPOSIÇÃO E FORMULAÇÃO TÓPICA ANESTÉSICA E SEU USO BR1020170113779 - Universidade Estadual de Campinas (UNICAMP) . Julio Cezar Pastre; Marili Vila Nova Rodrigues; Michelle Franz Montan Braga Leite ; Luiz Fernando Toneto Novaes; Verônica Santana de Freitas Blanco; Eneida de Paula; Isabella Gonçalves Alonso; Lais Thiemi Yamane ; Rodney Alexandre Ferreira Rodrigues - May 2017, 30