Chiroptical properties and conformation of N-acetyl-L-amino acids N'-methylamides with aliphatic side chains

Abstract

CD and 1H NMR spectra of L-alanine (I), L-leucine (II), L-valine (III) and L-tert-leucine (IV) N-acetyl N'-methylamides were measured at various experimental conditions involving changes of temperature, concentration and solvent polarity. The least flexible tert-leucine derivative IV exists predominantly either in right handed α-helical (αR) conformation (fluorinated alcohols, ethanol) or in extended (C5) conformation (cyclohexane, acetonitrile). In this compound the Φ angle is constrained to about -120°, excepting aqueous solution. The flexible amides I and II exhibit more complex conformational equilibria involving probably the 310, αR and C5 conformations. The 310 helical conformation is favoured in water, acetonitrile and non-fluorinated alcohols, while a higher participation of αR conformation is observed in strongly polar fluorinated alcohols. Conformational distribution of the valine derivatve III is similar to IV in fluorinated alcohols and to amides I and II in other solvents. The C7eq conformation is clearly detected only in cyclohexane solutions of non-associated forms of I and II.