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Design, Synthesis, NMR‐Solution and X‐Ray Crystal Structure of N ‐Acyl‐ γ ‐dipeptide Amides That Form a β II′‐Type Turn
Author(s) -
Brenner Meinrad,
Seebach Dieter
Publication year - 2001
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20010815)84:8<2155::aid-hlca2155>3.0.co;2-8
Subject(s) - chemistry , dipeptide , turn (biochemistry) , crystal structure , x ray , stereochemistry , proton nmr , crystallography , combinatorial chemistry , amino acid , biochemistry , physics , quantum mechanics
Conformational analysis of γ ‐amino acids with substituents in the 2‐position reveals that an N ‐acyl‐ γ ‐dipeptide amide built of two enantiomeric residues of unlike configuration will form a 14‐membered H‐bonded ring, i.e ., a γ ‐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 )‐ α ‐amino acids ( Scheme 1 ). Coupling two such γ ‐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 α ‐ to β ‐ to γ ‐peptides. Implications of the superimposable geometries of the actual turn segments (with amide bonds flanked by two quasi ‐equatorial substituents) in α ‐, β ‐, and γ ‐peptidic turns are discussed.