10.1016/S0040-4039(03)00072-8
The research describes the first total synthesis of dehydroaltenusin, a natural enzyme inhibitor, and its inhibitory activity against eukaryotic DNA polymerase. The synthesis involved several key chemicals and steps. It started from 2,4,6-trihydroxybenzoic acid, which was transformed into 1,3-benzodioxin via a reaction with diisopropyl azodicarboxylate-triphenyl phosphine in methanol. This compound was then methylated to form a monomethyl ether, which was subsequently converted into an aryl triflate using triflic anhydride and pyridine. Another important chemical, 4-bromocatechol, was prepared from 4-methylcatechol and subjected to methoxymethylation to form a bis-MOM ether. This compound underwent halogen–lithium exchange and reacted with triisopropyl borate to produce an aryl boronic acid. The aryl triflate and aryl boronic acid were coupled in the presence of tetrakis(triphenylphosphine)palladium, potassium phosphate, and potassium bromide to form a coupled product, which was then hydrolyzed and oxidized to yield dehydroaltenusin. The synthetic dehydroaltenusin showed inhibitory activity against DNA polymerase similar to that of the natural compound, with IC50 values of 0.8 and 0.7 μM for DNA polymerase α, respectively.
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