Synthesis and biological evaluation of bromophenol derivatives with cyclopropyl moiety: Ring opening of cyclopropane with monoester

Abstract

Trans-(1R*,2R*,3R*)-Ethyl 2-(3,4-dimethoxyphenyl)-3-methylcyclopropane-1-carboxylate (6) and its cis isomer 7 were obtained from the reaction of the methyl isoeugenol (5) with ethyl diazoacetate. The reduction and bromination reactions of the ester 6 and 7 together with the hydrolysis of all esters were carried out. Opening ring of cyclopropane was observed in the reaction of 7 with bromine. The opening of cyclopropane ring with COOR and synthesis of esters, alcohols and acids (6-26) are new. These obtained bromophenol derivatives (6-26) were effective inhibitors of the cytosolic carbonic anhydrase I and II isoforms (hCA I and II) and acetylcholinesterase (AChE) enzymes with Ki values in the range of 7.8 +/- 0.9-58.3 +/- 10.3 nM for hCA I, 43.1 +/- 16.7-150.2 +/- 24.1 nM for hCA II, and 159.6 +/- 21.9-924.2 +/- 104.8 nM for AChE, respectively. Acetylcholinesterase inhibitors are the most popular drugs applied in the treatment of diseases such as Alzheimer's disease, Parkinson's disease, senile dementia, and ataxia, among others.