Aggregation Behavior of 6-Isocassine and N-Methyl-6-Isocassine: Insights into the Biological Mode of Action of Lipid Alkaloids

Abstract

The aggregation behavior of 6-isocassine and N-methyl-6-isocassine, two piperidin-3-ol alkaloids isolated respectively from the barks of Prosopis nigra and P. affinis, was investigated using a combination of NOE experiments and diffusion measurements in solvents of varying polarity and hydrogen bonding capacity. While the NOE enhancements for N-methyl-6-isocassine are positive, regardless of the solvent, those for 6-isocassine shift from negative to positive when going from chloroform- d to methanol- d 4 solution. In addition, despite the self-diffusion coefficients of both compounds being virtually identical in methanol- d 4, N-methyl-6-isocassine diffuses nearly twice as fast as the non-methylated alkaloid in chloroform- d. The changes in rotational and translational dynamics observed between solvents for 6-isocassine suggest that the molecule forms dimeric head-to-head aggregates in non-polar aprotic environments, a behavior that could help explain the biological mode of action that has been proposed for this type of alkaloids.