4-arylbutan-2-ones: Starting Materials in the Synthesis of Novel Heme Oxygenase Inhibitors

Abstract

Synthetic organic chemistry and medicinal chemistry are the most significant fields of research in chemistry, where 4-arylbutan-2-ones find applications by allowing access to chemical entities otherwise difficult to synthesize, or in the de novo development of drug candidates. Structure-aided design based on previous results from our group has led to advances in shaping the structure of a series of novel imidazolebased heme oxygenase inhibitors. The practical generation of these inhibitors requires the synthesis of a set of 4-arylbutan-2-ones to be employed as starting materials in a reaction sequence that would afford in the end the desired imidazole-containing inhibitor target compounds. The present report illustrates the use of an one-step alkylation–cleavage synthetic approach toward such 4-arylbutan-2-ones featuring, in most cases, a hydrophobic para-substituent in the aromatic ring, starting from low-cost, commercially available organic reagents (pentane-2,4-dione and the suitably substituted benzyl bromides). The work described in this study represents an extension of a synthetic entry to this type of organic compounds, previously exploited in our group for the preparation of several structural analogs. The identity of the obtained 4-arylbutan-2- ones was established using nuclear magnetic resonance spectroscopy and high resolution mass spectrometry.

Keywords

• organic synthesis
• chemical intermediates
• ketones
• alkylation– cleavage
• structural investigation