Glycosylation of gossypol as a method to reduce its toxicity
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D. Mendeleev University of Chemical Technology, Moscow, Russia
MIREA Russian Technological University, Moscow, Russia
Publication date: 2021-09-27
Public Health Toxicol 2021;1(Supplement 1):A32

Gossypol is a naphthaldehyde with various types of physiological activity: antiviral, interferon-inducing, antitumor, antioxidant, etc. But along with this, gossypol is highly toxic. This work is devoted to the development of a method for chemical modification of gossypol to eliminate its toxicity while preserving its biological properties.
A method was developed for the synthesis of gossypol-containing compounds by glycosylation. The properties of the products formed as a result of the acid hydrolysis process, similar to the reaction in the acidic environment of the stomach, have been studied. Model substances containing gossypol were obtained by the Böeseken reaction in an alkaline medium. Briefly, a solution of gossypol in an alkaline medium was added to the glucose dissolved in a borate buffer. Then, the solutions were mixed and reacted at room temperature under argon flow for 48 hours. Then the mixture was washed to remove unreacted reagents and freeze-dryed. Acid hydrolysis of model glycosides was carried out at 37°C for 4 hours in a buffer solution containing hydrochloric acid (pH=2). The resulting water-insoluble apogossypol was separated by filtration and dried in air. The obtained compounds were investigated by 13C NMR and MALDI-TOF methods.
As a result of the condensation reaction of naphthaldehyde with glucose in a borate buffer, addition occurs at the C1 hydroxyl group of anomeric carbon atom of glucose. Addition to the C2, C3, C4 atoms does not occur. This is due to the orientational effect of the Böeseken complex used to ensure the regioselectivity of the reaction. During acid hydrolysis of model compounds, which are di-, tri-, and tetraglycosides in the form of complexes with boric acid, apogossypol and its oxidation products are formed. These substances are much less toxic due to the absence of aldehyde groups that cause cytotoxicity.
Thus, methods of synthesis were developed and model compounds of gossypol were characterized, which gives the right to further study the physiologically active compounds of gossypol from a biological point of view.