Structural modifications and detailed NMR studies of biologically active natural products

• Grant number: 09/09491-1
• Support Opportunities: Regular Research Grants
• Duration: April 01, 2010 - September 30, 2012
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Vladimir Constantino Gomes Heleno
• Grantee: Vladimir Constantino Gomes Heleno
• Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil

Abstract

In this project we propose to perform synthetic structural modifications in biologically active natural products (NP). These transformations will be undertaken with two different classes of NP: the diterpenes (kaurane and pimarane types) and the sesquiterpene lactones (SL), especially furanoheliangolides. The modifications have different objectives for the two target classes. With the diterpenes, the main objective is to obtain new derivatives to be submitted to different bioassays in which this class has already shown promising potential. The activities involved in this case are antimicrobial and atiespasmodic. In the other hand, for the SL, the main objective is to study the reaction of those substances with Stryker's reagent. This reaction was already successfully performed with a furanoheliangolide SL, yielding interesting cyclization and reduction products. Thus, here we intent to test the same reaction with different substrates. The obtained derivatives from SL, will be sent to anti-cancer and anti-inflammatory assays, in which other SL have already displayed interesting results. Those assays will be performed by co-workers. All obtained derivatives from both classes will be submitted to a detailed NMR study, which is one of the main objectives of this proposed work. The NMR study also has different challenges for each class. In the case of the SL, the main target is the complete and unequivocal 1H and 13C NMR data assignment, clarifying some doubtful previously published assignments and making an important data base available. For the diterpenes there is another important objective. The point is try to clarify all signals in the CH2 region in the 1H NMR spectra, using less common experiments and processing. This is a region of highly overlapped signals, what makes multiplicities hard to be observed and coupling constants almost impossible to be measured. In this case is also expected an important contribution to the data bases. For this, experiments like 1H-NMR, 13C-NMR {1H}, gCOSY, gHSQC, gHMBC, J-resolved, DPFGSE-NOE and others should be used. Data processing and spectra simulation programs will also be employed. (AU)

Scientific publications

(6)

(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)

SILVA, ALINE N.; SOARES, ANA CAROLINA F.; CABRAL, MIRELA M. W.; DE ANDRADE, ALEXR. P.; DA SILVA, MARILZA B. M.; MARTINS, CARLOS H. G.; VENEZIANI, RODRIGO C. S.; AMBROSIO, SERGIOR.; BASTOS, JAIRO K.; HELENO, VLADIMIR C. G.. Antitubercular Activity Increase in Labdane Diterpenes from Copaifera Oleoresin through Structural Modification. Journal of the Brazilian Chemical Society, v. 28, n. 6, p. 1106-1112, JUN 2017. (11/13630-7, 09/09491-1)

MATOS, PRISCILLA M.; MAHONEY, BRIAN; CHAN, YOHAN; DAY, DAVID P.; CABRAL, MIRELA M. W.; MARTINS, CARLOS H. G.; SANTOS, RAQUEL A.; BASTOS, JAIRO K.; PAGE, PHILIP C. BULMAN; HELENO, VLADIMIR C. G.. New Non-Toxic Semi-Synthetic Derivatives from Natural Diterpenes Displaying Anti-Tuberculosis Activity. Molecules, v. 20, n. 10, p. 18264-18278, OCT 2015. (11/13630-7, 09/09491-1)

FERREIRA SOARES, ANA CAROLINA; MATOS, PRISCILLA MENDONCA; DIAS, HERBERT JUNIOR; AGUIAR, GABRIELA DE PAULA; DOS SANTOS, ELIENE SILVERIO; GOMES MARTINS, CARLOS HENRIQUE; SOLA VENEZIANI, RODRIGO CASSIO; AMBROSIO, SERGIO RICARDO; GOMES HELENO, VLADIMIR CONSTANTINO. Variability of the antibacterial potential among analogue diterpenes against Gram-positive bacteria: considerations on the structure-activity relationship. Canadian Journal of Chemistry, v. 97, n. 7, p. 568-575, JUL 2019. (11/07885-2, 09/09491-1)

SOARES, ARTA CAROLINA F.; MATOS, PRISCILLA M.; DA SILVA, KARIME F.; MARTINS, CARLOS H. G.; VENEZIANI, RODRIGO C. S.; AMBROSIO, SERGIO R.; DIAS, HERBERT J.; DOS SANTOS, RAQUEL A.; HELENO, VLADIMIR C. G.. Antimicrobial Potential of Natural and Semi-Synthetic ent-Kaurane and ent-Pimarane Diterpenes against Clinically Isolated Gram-Positive Multidrug-Resistant Bacteria. Journal of the Brazilian Chemical Society, v. 30, n. 2, p. 333-341, FEB 2019. (09/09491-1, 11/07885-2)

SOARES, ANA C. F.; CABRAL, MIRELA M. W.; MARTINS, CARLOS H. G.; FERREIRA, ALEXSANDRO E.; BERGAMO, PEDRO A. S.; OMOSA, LEONIDA K.; MIDIWO, JACOB O.; PARREIRA, RENATO L. T.; HELENO, VLADIMIR C. G.. Study of Anti-Tuberculosis Activity Behaviour of Natural Kaurane and Trachylobane Diterpenes Compared with Structural Properties Obtained by Theoretical Calculations. NATURAL PRODUCT COMMUNICATIONS, v. 12, n. 5, p. 763-769, MAY 2017. (11/07623-8, 09/09491-1)

SASS, DAIANE CRISTINA; MORAIS, GUSTAVO OLIVEIRA; CREMA MIRANDA, RICARDO AUGUSTO; MAGALHAES, LIZANDRA GUIDI; CUNHA, WILSON ROBERTO; DOS SANTOS, RAQUEL ALVES; ARAKAWA, NILTON SYOGO; DA COSTA, FERNANDO BATISTA; CONSTANTINO, MAURICIO GOMES; GOMES HELENO, VLADIMIR CONSTANTINO. Structurally modified natural sesquiterpene lactones constitute effective and less toxic schistosomicidal compounds. ORGANIC & BIOMOLECULAR CHEMISTRY, v. 12, n. 40, p. 7957-7964, 2014. (09/09491-1)