Linear oligopeptides. 118. Preferred conformations and modes of self-association of the fluoren-9-ylmethoxycarbonyl amino acid derivatives

Abstract

An analysis of the preferred conformations and modes of self-association of the N-fluoren-9-methoxycarbonyl derivatives of L-alanine and α-aminoisobutyric acid was performed in solution and in the solid state using infrared absorption, 1H nuclear magnetic resonance, and X-ray diffraction. In a solvent of low polarity (deuterochloroform) non-associated and self-associated species (involving predominantly the hydroxyl and carbonyl groups of the carboxylic acid moiety) simultaneously occur. At high dilution, where self-association is absent, the amount of intramolecularly H-bonded forms, if any, should be extremely small. Z(trans) [Formula: see text]E(cis) isomerism about the amide bond of the secondary urethane moiety was observed only for the less bulky L-alanine derivative. In the solid state all H-bonding donors and acceptors of the L-alanine and α-aminoisobutyric acid derivatives take part to complex schemes of intermolecular H-bonds. In the L-alanine derivative, crystallized as monohydrate, most of the intermolecular H-bonds involve the water molecule. Intramolecular H-bonds are not observed in either compound. The conformation about the secondary urethane CO—NH bond is Z(trans) in both compounds. Both L-alanine and α-aminoisobutyric acid residues are partially folded. The observation of the long C(sp3)—O bond of the fluoren-9-yl-methoxycarbonyl moiety might contribute to explain the unexpected experimental result that this protecting group can be removed by catalytic hydrogenation.