Synthesis and Solid State Conformation of Tetrapeptide Amides Containing two Aib and two (αMe)Phe Residues - Use of Enantiomerically Pure 2-Benzyl-2-methyl-2H-azirin-3-amines as (αMe)Phe-Synthons.

ABSTRACT

A series of tetrapeptide amides containing two aminoisobutyric acids (Aib) and two α-methylphenylalanine ((αMe)Phe) units were prepared through the 'azirine/oxazolone method'. New 2-benzyl-2-methyl-2H-azirin-3-amines have been used for the selective introduction of (S)- and (R)-(αMe)Phe, respectively. The solid-state conformations of five tetrapeptide amides were determined by X-ray crystallography. In all cases, two ß-turns stabilize 310 -helical conformations and it was confirmed that, in contrast to proteinogenic amino acids, the configuration of (αMe)Phe does not determine the screw sense of the helix.