Conformational investigation of α,β‐dehydropeptides. XV: N ‐acetyl‐α,β‐dehydroamino acid N ′ N ′‐dimethylamides: conformational properties from infrared and theoretical studies

The FTIR spectra were analysed in the region of the ν s (NH), AI(CO) and ν s (C α C β ) bands for a series of Ac‐ΔXaa‐NMe 2 , where ΔXaa = ΔAla, ( Z )‐ΔAbu, ( Z )‐ΔLeu, ( Z )‐ΔPhe and ΔVal, to determine a predominant solution conformation of these α,β‐dehydropeptide‐related molecules. Measurements were taken in CCl 4 , DCM and MeCN solutions. In the same way, spectra of saturated analogues Ac‐Xaa‐NMe 2 , where Xaa = Ala, Abu, Leu, Phe and Val, were investigated. To help interpret the spectroscopic results, conformational maps were calculated by the B3LYP/6–31+G** method. Also, the relative energies of all conformers of the dehydro compounds in vacuo as well as in the studied solvents in addition to the theoretical IR frequencies of these conformers were calculated. For comparison, molecules of two saturated analogues, Ac‐ L ‐Ala‐NMe 2 and Ac‐ L ‐Phe‐NMe 2 , were calculated in a similar way. Both unsaturated and saturated compounds, which have an aliphatic side chain, occur in CCl 4 and DCM mainly as a mixture of extended conformers with the C 5 H‐bond and open conformers. As solvent polarity increases, participation of the open conformers also increases, and in MeCN, the model amides are almost exclusively in the open form, except Ac‐ΔAla‐NMe 2 , which shows a small amount of the H‐bonded conformer. Ac‐ΔAla‐NMe 2 and Ac‐ΔAbu‐NMe 2 have stronger C 5 hydrogen bonds than those of their saturated counterparts. As the calculations indicate, the open conformation of the unsaturated amides is conformer H/F with ϕ, ψ −44 ± 5°, 127 ± 4°. This is the second lowest in energy conformer in vacuo and in CCl 4 and the lowest one in more polar solvents. The open conformation of Ac‐ L ‐Ala‐NMe 2 constitutes conformer C with ϕ, ψ −101.5°, 112.7°. For Ac‐ΔAla‐NMe 2 and Ac‐ΔAbu‐NMe 2 , FTIR also reveals the presence of a third conformer. Calculations indicate that is the semiextended conformer D with the N 1 ‐H 1 ···N 2 hydrogen bond/contact. In all solvents, Ac‐ L ‐Phe‐NMe 2 and Ac‐( Z )‐ΔPhe‐NMe 2 show only the extended E and the open H/F, respectively. In both there is an amide/π(Ph) interaction. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.