Nonivamid scale-up szintézise és különböző kapszaicinoidok komplexációs vizsgálata különböző ciklodextrinekke
Cyclodextrins (CDs), as cyclic oligosaccharides are regularly applied as inclusion complexes in order to increase the solubility and bioavailability of poorly water-soluble APIs. Capsaicinoids are widely used as food additives, however, they can also be used as analgesics, and they are also promising in the treatment of prostate cancer and in plant protection. In general, capsaicinoids have low water solubility, which can be improved by their complexations with CDs.
The aim of our research work was the investigation of the inclusion complexations of different capsaicinoids (capsaicin, dihydrocapsaicin, nonivamide) with various substituted β-cyclodextrins (CDs). Scale-up synthesis of a famous capsaicinoid, called nonivamide, was performed to obtain a guest molecule for the further complexations. Synthesis consisted of two different reactions steps: the activation of the corresponding fatty acid and the N-acylation of the vanillyl amine compound. During this process, such reaction conditions as the role of the vanillyl amine hydrochloride salt and the free base form of vanillyl amine, the amount of the reagents, the reaction time and different solvents were investigated.
In the next part of our work, the inclusion complexations were studied. First, phase solubility tests were performed in order to find out the appropriate API and CD concentrations for the complexation reactions. With the optimal conditions in hand, we prepared several complexes.
The nonivamide synthesis was followed by mass spectrometer coupled column chromatography (HLPC-MS) and gas chromatography (GC). The phase solubility studies were analyzed by HPLC measurements and the complexes were studied by 1H NMR and HSQC spectroscopy.
