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

• Published in: Memoirs of the Scientific Sections of the Romanian Academy Vol. XLVI; pp. 229 - 240
• Main Authors: Gheorghe Roman, Walter A. Szarek
• Format: Journal Article
• Language: English
• Published: Publishing House of the Romanian Academy 01.11.2023
• Subjects: alkylation– cleavage; chemical intermediates; ketones; organic synthesis; structural investigation
• ISSN: 1224-1407; 2343-7049

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.