I. Interaction between asymmetric solutes and solvents: dipeptides as solvents. II. The solid phase synthesis of amidated peptides



Journal Title

Journal ISSN

Volume Title



The interaction of a dipeptidic phase, N-trifluoroacetyl-L-phenylalanyl-L-leucine cyclohexyl ester (I), with solutes, consisting of N-trifluoroacetyl (N-TFA) and N-pentafluoropropionyl (N-PFP) esters of [proportional to]-amino acids, has been studied at 100-130[degrees]C. The difference in behavior, as judged by the separation factors of enantiomers, between (I) and N-TFA-L-valyl-L-valine cyclohexyl ester (II), depends on the compound used for comparison. The following regularities were observed: (1) Resolution improves as the alkyl residue of the ester function of the solute increases from a primary to a secondary to a tertiary group. (2) The alkyl radical attached to the asymmetric carbon of the solute decreases resolution when substituted in the [beta]-position (with respect to the carboxylic group), while the reverse is true of substitution of the [gamma]-position. (3) Under the same conditions, N-PFP derivatives have about 25% lower retention volumes throughout than corresponding N-TFA esters. Because of the higher volatility of N-PFP derivatives, arginine, cysteine, lysine and tryptophan are resolved in either 100 ft or 400 ft columns. The advantage of the N-PFP derivatives is that they have shorter retention times without a significant loss in the resolution factors. The influence of the perfluoroacyl,heptafluoroutyl and pentadecaoctanoyl derivatives of amino acid esters, other than trifluoroacetyl group, with respect to retention times and resolution factor has also been studied.