Post-Functionalization of Small Ply-functionalized Molecules: A Robust Approach to the Synthesis of New Structural Patterns with POtential Biological Activity

• Grant number: 18/02611-0
• Support Opportunities: Regular Research Grants
• Start date: May 01, 2018
• End date: April 30, 2020
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Fernando Antonio Santos Coelho
• Grantee: Fernando Antonio Santos Coelho
• Host Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated researchers: Adriano Defini Andricopulo ; Nilton Soares Camilo ; Wanda Pereira Almeida

Abstract

This research project intends to continue the development of a line of research that explores the Morita-Baylis-Hillman (MBH) reaction, which is an organocatalysed process of formation of a new C-C Ã bond, leading to the synthesis of small poly-functionalized, which can be used as substrate for other chemical transformations. The research proposal was divided into two main projects and each of them divided into subprojects. In the first project, we intend to explore the general aspects of this reaction by initially testing its behavior in the presence of Bronsted acids. Although the usual catalysts of the Morita-Baylis-Hillman reaction may give rise to a very rapid acid-base reaction, preliminary results show a considerable increase in both the reaction rate and the yields, especially with aromatic aldehydes substituted with electrons donating groups, which behave very badly in this reaction. We also intend to explore novel bi-functional Lewis bases as catalysts for an asymmetric version of an MBH reaction between isatin and cycloenones. In the second project we intend to explore the use of adducts as substrates for the synthesis of pyrido-indolones, poly-functionalized dienes, macrolactones and macrolactams using novel synthetic approaches. The products obtained in this part of the proposal will be evaluated against triple negative human breast cancer cells. They will also be evaluated as inhibitors of acetylcholinesterase and against the parasites that cause malaria and leishmaniasis. (AU)

Scientific publications

(14)

(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)

ZEOLY, LUCAS A.; ACCONCIA, LAIS V.; RODRIGUES JR, MANOEL T.; SANTOS, HUGO; CORMANICH, RODRIGO A.; PANIAGUA, JUAN C.; MOYANO, ALBERT; COELHO, FERNANDO. One-pot organocatalyzed synthesis of tricyclic indolizines. ORGANIC & BIOMOLECULAR CHEMISTRY, v. 21, n. 17, p. 15-pg., 2023-04-14. (13/07600-3, 14/26027-5, 13/24386-5, 18/02611-0, 15/00975-7, 15/09205-0)

RODRIGUES JR, MANOEL T.; SANTOS, HUGO; ZEOLY, LUCAS A.; SIMONI, DEBORAH A.; MOYANO, ALBERT; COELHO, FERNANDO. Preparation of tetrahydro-1H-xanthen-1-one and chromen-1-one derivatives via a Morita-Baylis-Hillman/oxa-Michael/elimination cascade. ARKIVOC, n. 2, p. 77+, 2020. (13/07600-3, 15/09205-0, 18/02611-0, 17/02364-0)

FERNANDES, FABIO S.; SANTOS, HUGO; LIMA, SAMIA R.; CONTI, CAROLINE; RODRIGUES JR, MANOEL T.; ZEOLY, LUCAS A.; FERREIRA, LEONARDO L. G.; KROGH, RENATA; ANDRICOPULO, ADRIANO D.; COELHO, FERNANDO. Discovery of highly potent and selective antiparasitic new oxadiazole and hydroxy-oxindole small molecule hybrids. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, v. 201, SEP 1 2020. (18/02611-0, 13/07600-3, 16/23005-6, 15/09205-0)

CAMILO, NILTON S.; SANTOS, HUGO; ZEOLY, LUCAS A.; FERNANDES, FABIO S.; RODRIGUES JR, MANOEL T.; SILVA, THIAGO S.; LIMA, SAMIA R.; SERAFIM, JOSE CLAUDIO; DE OLIVEIRA, ALINE S. B.; CARPANEZ, ARTHUR G.; et al. An Improved Protocol for the Morita-Baylis-Hillman Reaction Allows Unprecedented Broad Synthetic Scope. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, v. N/A, p. 9-pg., 2022-01-19. (18/00299-0, 18/02611-0, 16/23005-6, 13/07600-3, 15/09205-0)

SILVA, THIAGO S.; RODRIGUES, JR., MANOEL T.; SANTOS, HUGO; ZEOLY, LUCAS A.; ALMEIDA, WANDA P.; BARCELOS, ROSIMEIRE C.; GOMES, RALPH C.; FERNANDES, FABIO S.; COELHO, FERNANDO. Recent advances in indoline synthesis. Tetrahedron, v. 75, n. 14, p. 2063-2097, APR 5 2019. (15/09205-0, 18/02611-0, 13/07600-3, 16/23005-6)

LIMA, SAMIA R.; COELHO, FERNANDO. Synthesis of 1,4,6-Tricarbonyl Compounds via Regioselective Gold(I)-Catalyzed Alkyne Hydration and Their Application in the Synthesis of alpha-Arylidene-butyrolactones. ACS OMEGA, v. 5, n. 14, p. 8032-8045, APR 14 2020. (18/02611-0, 13/07600-3)

CAPRETZ-AGY, ANDRE; FERNANDES, FABIO S.; RODRIGUES JR, MANOEL T.; CONTI, CAROLINE; COELHO, FERNANDO. Aza-Morita-Baylis-Hillman Reaction with Vinyl-oxadiazoles: An Expeditious Approach to Access New Heterocyclic Arrangements. Synlett, v. 31, n. 6, p. 622-626, APR 1 2020. (18/02611-0, 13/07600-3, 16/23005-6)

SILVA, THIAGO S.; COELHO, FERNANDO. Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances. Beilstein Journal of Organic Chemistry, v. 17, p. 1565-1590, JUL 7 2021. (13/07600-3, 18/02611-0)

FERNANDES, FABIO S.; RODRIGUES, JR., MANOEL T.; ZEOLY, LUCAS A.; CONTI, CAROLINE; ANGOLINI, CELIO F. F.; EBERLIN, MARCOS NOGUEIRA; COELHO, FERNANDO. Vinyl-1,2,4-oxadiazoles Behave as Nucleophilic Partners in Morita-Baylis-Hillman Reactions. Journal of Organic Chemistry, v. 83, n. 24, p. 15118-15127, DEC 21 2018. (18/02611-0, 13/07600-3, 16/23005-6)

SILVA, THIAGO S.; ZEOLY, LUCAS A.; COELHO, FERNANDO. Catalyst-Free Conjugate Addition of Indolizines to In Situ-Generated Oxidized Morita-Baylis-Hillman Adducts. Journal of Organic Chemistry, v. 85, n. 8, p. 5438-5448, APR 17 2020. (18/02611-0, 13/07600-3)

DA SILVA, THIAGO SABINO; SOUZA, MATHEUS DA SILVA; ANDRICOPULO, ADRIANO DEFINI; COELHO, FERNANDO. Discovery of indolizine lactones as anticancer agents and their optimization through late-stage functionalization. RSC ADVANCES, v. 13, n. 29, p. 7-pg., 2023-06-29. (18/02611-0, 22/00219-1, 13/07600-3, 18/25289-7)

SENNA, ANA JULIA S.; RODRIGUES JR, MANOEL T.; SANTOS, HUGO; ZEOLY, LUCAS A.; GOMES, RALPH C.; COELHO, FERNANDO. 1,6-Addition of indolizines to para-quinone methides with indium(III) chloride as catalyst. Tetrahedron Letters, v. 125, p. 6-pg., 2023-07-05. (13/07600-3, 18/02611-0, 15/09205-0)

GUIDOTTI, BRUNO BONI; DA SILVA, THIAGO SABINO; MENEZES CORREIA, JOSE TIAGO; COELHO, FERNANDO. Bronsted-acid-catalyzed selective Friedel-Crafts monoalkylation of isatins with indolizines in water. ORGANIC & BIOMOLECULAR CHEMISTRY, v. 18, n. 37, p. 6-pg., 2020-10-07. (13/07600-3, 18/02611-0)

RODRIGUES JR, MANOEL T.; SANTOS, HUGO; ZEOLY, LUCAS A.; SIMONI, DEBORAH A.; MOYANO, ALBERT; COELHO, FERNANDO. Preparation of tetrahydro-1H-xanthen-1-one and chromen-1-one derivatives via a Morita-Baylis-Hillman/oxa-Michael/elimination cascade. ARKIVOC, v. N/A, p. 60-pg., 2020-01-01. (17/02364-0, 13/07600-3, 18/02611-0, 15/09205-0)