Estudo teórico-experimental por RMN da elucidação estrutural de alcaloides isoquinolínicos

Abstract

The isoquinolinic alkaloids of the Amaryllidaceae family are secondary metabolites known for their antitumor, antimalarial and other activities. Structural elucidation of these molecules is essential for the analysis of potential future drugs. Then, the use of spectroscopic techniques, such as Nuclear Magnetic Resonance (NMR), where the chemical shift () and the coupling constant (J) are some of its fundamental properties obtained. However, in some cases, the assignments of and J can be complicated due to the structural complexity of some molecules, requiring the use of molecular modeling (MM) techniques for the extraction of structural and electronic properties, such as the ab initio methods. Among the best known ab initio methods, we can mention, from the Hartree-Fock (HF) and the DFT (Density Functional Theory), with its functional B3LYP, to the most recent ones such as the Hartree-Fock 3c and the B97- 3c, published in 2018. Thus, in this work, analyzes of the one-dimensional (¹H NMR and ¹³C NMR and DEPT-135) and two-dimensional (COSY, HMBC, HSQC and NOESY) NMR spectra of the isoquinoline alkaloids haemantamine (A) were performed, aulicin (B). In addition, theoretical calculations of chemical displacement and coupling constants at the DFT-GIAO/B3LYP/cc-pVDZ//PBE0/TZ2P level were performed taking into account the effect of the implicit solvent and vacuum for the compounds haemantamine (A), aulicin (B). Regarding the calculated H and C values, better SD, MAE, CMAE and R values were observed for the B3LYP/cc-PVDZ model and for the calculated J values there was better correspondence for the PBE0/TZ2P model. For compound A, the best performance of the best performance, the solvent B3LYP with the solvent stood out for the best effect of the first δH (SD = 0.20, MAE = 0.20; CMAE = 0.9842) and of δC (R = 0.9984; SD = 3.57, MAE = 6.96 and CMAE = 6.96). For compound B, for the PBE0/TZ2P level, better maintenance of H (SD = 0,18; MAE = 0,19; CMAE = 0,08 e R = 0,9645) e C (SD = 3,83; MAE = 5,21; CMAE = 4,79 e R = 0,9948). Thus, computational calculations together with experimental data aim to facilitate the structural elucidation of the molecules studied.