Organosulfur Compounds as Chiral Building Blocks

Synthesis and Preliminary Screening of the Biological Activity of Sulindac Sulfoximine Derivatives

“…Nowadays, considerable interest is attached to the molecular class of sulfoximines [14,15], compounds that are isosteres with sulphones. Sulfoximines are small hydrophilic molecules with a sulfur atom in a stable configuration also connected to a nitrogen atom that is nucleophilic and basic.…”

“…The resulting availability of sulfoximines has encouraged new investigations into the applications of these compounds as bioactive compounds. A recent review highlighted the opportunity connected to sulfoximines in the period 2013-2020, analyzing the enzymes that could be inhibited [14,15]. Compounds containing the sulfoximine group showed interesting activities as anti-asthmatics, spasmolytics, benzodiazepine receptor partial agonists, and COX-2 enzyme inhibitors.…”

“…This oxidation protocol has proved to be very useful for the synthesis of different types of chiral sulfoxides obtainable in good yields with high enantiomeric purity. In this context, we reported the Nowadays, considerable interest is attached to the molecular class of sulfoximines [14,15], compounds that are isosteres with sulphones. Sulfoximines are small hydrophilic molecules with a sulfur atom in a stable configuration also connected to a nitrogen atom that is nucleophilic and basic.…”

“…Sulfoximines were synthesized for the first time more than seventy years ago, but they were seldom employed on a large scale until new and effective synthetic methods were discovered [15][16][17][18][19]. For example, a simple protocol of wide applicability for the synthesis of sulfoximines is based upon the reaction of the corresponding sulfoxides with PhI(OAc) 2 as the oxidant and solutions of ammonium carbamate as the N source.…”

“…Then, the esters were hydrolyzed to yield chiral sulindac (2a) [20]. Taking into account all these aspects, and our experience of the synthesis of racemic and enantiopure sulfoxides [15,19,20], and in particular of sulindac alkyl esters [20] and of sulfoximine [19], we decided to synthesize the sulfoximines of sulindac derivatives and to test the bioactivity of these compounds, in which the anti-inflammatory sulindac is combined with the new possibilities connected with the sulfoximine moiety.…”