Abstract

Oxaline is a bioactive alkaloid that acts as an antibiotic and antiproliferative drug affecting tubulin polymerization. Oxaline and meleagrine alkaloids contain an indoline spiroaminal tricyclic system produced from roquefortine as a biosynthetic precursor. These prenylated indoline spiroaminal alkaloids have been identified mainly by NMR spectroscopy and single crystal X-Ray diffraction. The 1H NMR spectrum of the parent alkaloid roquefortine contains three clear signals for vinyllic hydrogens forming an ABX system and two clear and intense singlets for methyl groups at the prenyl unit. On the other hand, the indoline spiroaminal alkaloids produce 1H NMR containing these same signals but they are formed of broad lines, many times as uninterpretable signals. Although it appears that these unusual signals have not become an important obstacle for correct identification of these alkaloids, nonetheless this broadening line phenomenon has not yet been addressed and correctly figured out. In the present study we applied some computational tools contributing to enhance the understanding of this phenomenon. The Density Functional Theory (DFT) studies of interatomic distances, electron density and electrostatic potential distributions led us to consideration of the possible effect of the quadrupolar field of the nitrogen atoms, especially N-14 and N-11, which are the closest to the prenyl hydrogen atoms. The poor resolution in these signals varies with the solvent and the temperature changes. In addition to conformational mobility, our studies also considered the influence of the quadrupolar field of the nitrogen atoms from the triazaspirocycle system on the resonances of neighbor hydrogens. It is known from the literature that the lines of ½ spin nuclei such as 1H attached to nitrogen (I = 1) have their line-shape, multiplicity and relaxation time affected. In the case of these spiroaminal indoline alkaloids, we found that the 1H nuclei from the prenyl group are affected through space, since they are not directly attached to any of the three quadrupolar-N.