Benzoylation of gossypol using benzoyl chloride and benzoic anhydride as acylating agents

Abstract

To understand deeply the process of acylation of natural polyphenol gossypol, its stepwise benzoylation was performed using benzoyl chloride and benzoic anhydride as acylating agents in the presence of pyridine-N-oxides. The influence of the composition of a reaction mixture on the benzoylation process and reaction products was analyzed by the method of reversed-phase high-performance liquid chromatography. It was established that benzoylation of gossypol leads to the tautomeric transition of the respective fragment from aldehyde to lactol tautomeric form. This transition is most likely due to the breaking of the hydrogen bond C(7)–OHO=C(11) in combination with the displacement of the aldehyde group by the benzoyl fragment from the naphthyl ring plane (in the case of benzoylation of C(7)–OH group); benzoylation of C(6)–OH group is accompanied by the breaking of the hydrogen bond C(6)–OHO–C(7). These changes of configuration significantly facilitate the proton transfer from the C(1)–OH group to oxygen at C(11) followed by the formation of the lactol cycle. The use of benzoyl chloride as an acylating agent in combination with triethylamine and 4-methoxypyridine-N-oxide allows benzoylating gossypol quickly. However, the variety of formed benzoates is quite large because of the similar reactivity of different hydroxyl groups. In the case of benzoic anhydride, the number of isomeric gossypol benzoates remains quite high. Much more esters with higher retention time are accumulated due to a higher degree of benzoylation.