Structural modifications and detailed NMR studies of biologically active natural products

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)