Synthesis of purpurogallin-formic acid ester derivatives and their formation mechanism

Bicyclo[3.2.1]octane-type intermediates (BOIs) play a crucial role in theaflavin (TFs) synthesis via decarboxylation with water. Given this reactivity, it is hypothesized that BOIs can also react with other polar solvents such as alcohols to yield the corresponding analogs. In this study, pyrogallol (PG) was employed as the substrate with Ag2O as the oxidant to synthesize BOIPPG in an acetone system. Subsequently, this intermediate reacts with a variety of alcohols to yield diverse purpurogallin (PPG) formate derivatives with substitutions at the e and c positions. In addition, PG was converted into PPG-ethanol analogs under specific enzymatic conditions. By examining the structures of the synthesized compounds in conjunction with quantum mechanics, we propose a novel detailed mechanism for the generation of BOIs into benzotropolone (BTP) derivatives. This mechanism effectively accounts for the variations in the product yields observed in our experimental studies. The bicyclo [3.2.1] octane-type intermediate (BOI) plays a crucial role in the production of benzotropolone derivatives. BOIPPG, derived from PG oxidation, can undergo decarboxylation in the presence of water to form purpurogallin (PPG) (Route A2 and B1). Conversely, reaction of this intermediate with alcohol lead to dehydrogenation, producing ester derivatives (Route A1-1). Additionally, upon protonation at the c-position, especially when R is methyl, the formation of a carbocation facilitates hydroxylation, resulting in the by-product 20 (Route A1-2). Enzymatic oxidation of PG requires catechol for the formation of the corresponding ethanol derivative. This highlights that polar solvents facilitate attack on the bridging carboxyl carbon, leading to cleavage of the C2–C3 bond (compound 11–1) in the presence of a strong oxidant, with o-quinone substituting PG-quinone. The efficiency of proto dissociation in polar solvents significantly influences compound yields. Alcohols, featuring electron-donating alkyl chains, face heightened challenges in deprotonating their hydroxyl groups, thereby reducing product yields. Moreover, longer alkyl chains in alcohols further diminish yields. [Display omitted] The conversion of the bicyclo[3.2.1]octane intermediate to benzotropolone has been successfully demonstrated.