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Synthesis and Functionalization of Cyclic Sulfonimidamides: A Novel Chiral Heterocyclic Carboxylic Acid Bioisostere

By Nils Pemberton (2065462), Henrik Graden (2065468), Emma Evertsson (1692748), Emma Bratt (1814542), Matti Lepistö (2065465), Petra Johannesson (2012890) and Per H. Svensson (1720264)


An efficient synthesis of aryl substituted cyclic sulfonimidamides designed as chiral nonplanar heterocyclic carboxylic acid bioisosteres is described. The cyclic sulfonimidamide ring system could be prepared in two steps from a trifluoroacetyl protected sulfinamide and methyl ester protected amino acids. By varying the amino acid, a range of different C-3 substituted sulfonimidamides could be prepared. The compounds could be further derivatized in the aryl ring using standard cross-coupling reactions to yield highly substituted cyclic sulfonimidamides in excellent yields. The physicochemical properties of the final compounds were examined and compared to those of the corresponding carboxylic acid and tetrazole derivatives. The unique nonplanar shape in combination with the relatively strong acidity (p<i>K</i><sub>a</sub> 5–6) and the ease of modifying the chemical structure to fine-tune the physicochemical properties suggest that this heterocycle can be a valuable addition to the range of available carboxylic acid isosteres

Topics: Biophysics, Biochemistry, Medicine, Biotechnology, Evolutionary Biology, Plant Biology, Environmental Sciences not elsewhere classified, Biological Sciences not elsewhere classified, Chemical Sciences not elsewhere classified, Novel Chiral Heterocyclic Carboxylic, chiral nonplanar heterocyclic carboxylic acid bioisosteres, cyclic sulfonimidamides, cyclic sulfonimidamide ring system, carboxylic acid isosteres, compound, physicochemical properties, aryl
Year: 2012
DOI identifier: 10.1021/ml3000935.s001
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Provided by: FigShare
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