No abstract

Amino acids with side chains in the 2-, 3-, and 4-positions, prepared by addition of acyloxazolidinones to a nitroolefin and hydrogenation, have been coupled to gtetra-, and g-hexapeptides which are shown to form (M)-2.6 14 helices in the crystal state and in MeOH solution.

Conformational analysis of g-amino acids with substituents in the 2-position reveals that an N-acyl-gdipeptide amide built of two enantiomeric residues of unlike configuration will form a 14-membered H-bonded ring, i.e., a g-peptidic turn (Figs. 1 ± 3). The diastereoselective preparation of the required building blocks was achieved by alkylation of the doubly lithiated N-Boc-protected 4-aminoalkanoates, which, in turn, are readily available from the corresponding (R)-or (S)-a-amino acids (Scheme 1). Coupling two such g-amino acid derivatives gave N-acetyl and N-[(tert-butoxy)carbonyl] (Boc) dipeptide methyl amides (1 and 10, resp.; Fig. 2, Scheme 2); both formed crystals suitable for X-ray analysis, which confirmed the turn structures in the solid state ( Fig. 4 and Table 4). NMR Analysis of the acetyl derivative 1 in CD 3 OH, with full chemical-shift and coupling assignments, and, including a 300-ms ROESY measurement, revealed that the predicted turn structure is also present in solution ( Fig. 5 and Tables 1 ± 3). The results described here are yet another piece of evidence for the fact that more stable secondary structures are formed with a decreasing number of residues, and with increasing degree of predictability, as we go from a-to b-to g-peptides. Implications of the superimposable geometries of the actual turn segments (with amide bonds flanked by two quasi-equatorial substituents) in a-, b-, and g-peptidic turns are discussed.

No abstract

Dedicated to Professor Siegfried Hünig with best wishes on the occasion of his 80th birthday g 4 -Tripeptides and g 4 -hexapeptides, 1 ± 4, with OH groups in the 2-or 3-position on each residue have been prepared. The corresponding 2-hydroxy amino acids were obtained by Si-nitronate (3 2) cycloadditions to the acryloyl derivative of Oppolzers sultam and Raney-Ni reduction of the resulting 1,2-oxazolidines (Scheme 1). The 3-hydroxy amino acid derivatives were prepared by chain elongation via Claisen condensation of Boc-Ala-OH, Boc-Val-OH, and Boc-Leu-OH, and NaBH 4 reduction of the methyl 4-amino 3-oxo carboxylates formed (Scheme 2). The N-Boc hydroxy amino acids were coupled in solution to give the g-peptides. CD Spectra of the new types of g-peptides were recorded and compared with those of simple g 2 -, g 3 -, g 4 -, and g 2,3,4 -peptides (Figs. 3, 4, and 5). An intense Cotton effect at ca. 200 nm ([V] À 2´10 5 deg´cm 2´d mol À1 ) indicates that the hexapeptide built of (3R,4S)-4-amino-3-hydroxy acids (with the side chains of Val, Ala, Leu) folds to a secondary structure so far unknown. The stability of peptides from b-and g-amino acids, which carry heteroatoms on their backbones is discussed (Fig.