Design, synthesis, identification, and spectroscopic study of the structure and tautomerism of gossypol imine derivatives

Gossypol, a natural polyphenolic compound, is considered a promising scaffold for the design of biologically active derivatives with pronounced antioxidant properties. In this study, newly synthesized gossypol imine derivatives were investigated in order to elucidate their structural features and tautomeric behavior.

Five newly synthesized gossypol imine derivatives were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Positive and negative ion mode mass spectra were recorded using 2,4,6-trihydroxyacetophenone (THAP) as the matrix. Structural features and tautomerism were additionally studied by ¹H and ¹³C NMR spectroscopy in DMSO-d6 solution.

The THAP matrix significantly enhanced the intensities of molecular ion peaks, including protonated/deprotonated species and sodium or potassium adducts, while simultaneously reducing fragmentation in both ionization modes (compared to matrix-free mode). This enabled reliable confirmation of the structures of the newly synthesized imine derivatives. Characteristic chemical shifts in the ¹H and ¹³C NMR spectra, indicative of dienamine and diimine tautomeric forms, were identified. It was established that gossypol Schiff bases predominantly exist in the dienamine tautomeric form, whereas gossypol hydrazones mainly adopt the diimine form in solution. Furthermore, all hydroxyl groups of the gossypol fragment were involved in the formation of intramolecular hydrogen bonds of different strength.

Design, synthesis, study of the structure and physicochemical properties of biologically active compounds on the basis of natural polyphenols from renewable raw materials is an economically sound basis and a necessary chemical step in the development of effective drugs.