A MACROCYCLE CONTAINING TWO BIPHENYL AND TWO ALANINE SUBUNITS, SYNTHESIS AND CONFORMATION IN SOLUTION

Article abstract of DOI:10.1016/0040-4020(89)80135-8

The synthesis and solution conformation of the macrocycle cyclo(-2-Ala)2 3 is presented.The compound 3 contains two alanine and two molecules of the novel pseudoamino acid 2-aminomethyl-2'-carboxymethylbiphenyl 2 in the ring.A phthalimido-protected derivative of 2 is obtained in three steps from diphenic anhydride.The compound 2 is coupled to H-AlaOCH3 and the resulting "dipeptide" dimerizes at the conditions of an azide coupling to 3 (20percent).The macrocycle 3 exists in three diastereomeric forms 3A, 3B and 3C which can be separated by HPLC.The form with R,S configuration of the biphenyl groups has C1 symmetry (3C).The one- and two-dimenzional 1H-NMR data of 3C support a structure where the biphenyl groups are orientated in an orthogonal arrangement.One alanine is in an equatorial C7 conformation, the other alanine is part of a stretched peptide chain.The forms 3A and 3B with C2 symmetry exist probably as equilibrating structures in solution.The NMR data can be explained with β-sheet conformations as well as with more bent structures containing γ-loops.