Synthesis and QSAR of thia-Derivatives of Aroylacrylic Acids

Syntheses of thirty-one aroylacrylic acids twenty-seven 2-[(carboxymethyl)sulfanyl]-4-oxo-4-arylbutanoic acids (CSAB) three 2-[(2-carboxyethyl)sulfanyl]-4-oxo-4-arylbutanoic acids one 2-[(1-carboxyethylsulfanyl]-4-oxo-4-arylbutanoic acid one 2-[(2-methoxy-2-oxoethyl)sulfanyl]-4-oxo-4-arylbutanoic acid and one 2-ethoxycarbonylmethylsulfanyl]-4-oxo-4-arylbutanoic acid are described. Conformational preferences of CSAB in polar and non-polar solvents DMSO and chloroform are examined. Analysis of conformational preferences in solution (NAMFIS analysis) is performed using 1H NMR NOESY J-HMBC spectra and conformational assemblies of compound obtained by CS in Macro Model and OMEGA. Most abound conformers in non-polar chloroform have an extended shape - largest part of apolar surface area of molecules are exposed to solvent. Advantages of methods based on 3D structure of compounds for the estimation of n-octanol/water partition coefficients (logP values) are briefly outlined. In 'extended' conformations divalent S atom could form non-covalent intermolecular interactions with other heteroatoms (O N) in closest proximity.