Enantioresolution and stereochemical characterization of two chiral sulfoxides endowed with COX‐2 inhibitory activity

• Published in: Chirality (New York, N.Y.) N.Y.), 2017-09, Vol.29 (9), p.536-540
• Main Authors: Sardella, Roccaldo, Ianni, Federica, Di Michele, Alessandro, Di Capua, Angela, Carotti, Andrea, Anzini, Maurizio, Natalini, Benedetto
• Format: Article
• Language: English
• Subjects: Absolute configuration; Biosynthesis; Cellulose; Circular dichroism; COX-2 inhibitors; Cyclooxygenase 2 - metabolism; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2; electronic circular dichroism; Elution; enantiomeric elution order; Enantiomers; Inhibition; Nonsteroidal anti-inflammatory drugs; polar‐organic mode of elution; polysaccharide cellulose‐based stationary phase; Prostaglandins; Stationary phase; Stereoisomerism; Stilbene; Sulfoxides; Sulfoxides - chemistry; Sulfoxides - pharmacology
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.22724

The capacity of nonsteroidal antiinflammatory drugs (NSAIDs) to prevent prostanoids biosynthesis through the inhibition of COX‐2 enzyme is related to their structural backbone, based on the fusion of a cis‐stilbene unit with a variety of heterocyclic and carbocyclic rings. By this route, a series of new selective COX‐2 inhibitors was developed, by maintaining the 4‐methylsulfone or 4‐methylsulfonamide substituent on the phenyl moiety, essential for their activity. In this frame, two novel propyl sulfoxide derivatives were synthesized, which proved selective and sufficiently potent COX‐2 inhibition activity when tested as racemates. In the present study, the use of a cellulose tris(3,5‐dichlorophenylcarbamate)‐based chiral stationary phase, in a polar‐organic mode of elution, enabled the successful enantioseparation of the investigated compounds. The developed chromatography method reveals a useful tool of monitoring in view of a proper forthcoming enantioselective synthetic protocol. Moreover, the optimized chromatographic conditions allowed the isolation of appropriate amounts of single enantiomers for the electronic circular dichroism studies that, coupled with in silico simulations, allowed assessing the absolute configuration of each species.