Collection of Czechoslovak Chemical Communications - digital archive 

Abstract

The methylation of tert-butyl- or isopropyl- esters of N^α-4-toluenesulfonyl-amino acids by dimethylsulfate in aqueous alkaline solution in the presence of a detergent gives the corresponding N^α-methylderivatives. Using this synthetic route the N^α-acetylderivatives of MeAla, MeLeu, MeOrn and MePhe methylamides have been prepared and the solution conformation of these dipeptide units has been investigated. ¹H and ¹³C NMR spectra show that, while in dimethylsulfoxide the tertiary amide group is mostly in cis-conformation, in protic solvents the equilibrium is shifted towards trans-conformation. Circular dichroism spectra reveal some specific features (e.g. high band intensities in protic solvents) which cannot be explained solely on the basis of the increased rigidity caused by the N^α-methyl group. We tried to explain these effects supposing that the tertiary amide group is deviated from the planar arrangement (due to the interaction between the methyl groups, a substituent on C^α and a solvent molecule attached to the oxygen atom) and contributes to the observed circular dichroism as the inherently chiral chromophore.