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Synthesis and CD Spectra in MeCN, MeOH, and H 2 O of γ ‐Oligopeptides with Hydroxy Groups on the Backbone, Preliminary Communication
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(20010516)84:5<1181::aid-hlca1181>3.0.co;2-0
Subject(s) - chemistry , tripeptide , amino acid , stereochemistry , side chain , dipeptide , oligopeptide , residue (chemistry) , heteroatom , peptide , organic chemistry , ring (chemistry) , biochemistry , polymer
γ 4 ‐Tripeptides and γ 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 Oppolzer 's 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 γ ‐peptides. CD Spectra of the new types of γ ‐peptides were recorded and compared with those of simple γ 2 ‐, γ 3 ‐, γ 4 ‐, and γ 2,3,4 ‐peptides ( Figs. 3 , 4 , and 5 ). An intense Cotton effect at ca . 200 nm ([ Θ ]=−2⋅10 5 deg⋅cm 2 ⋅dmol −1 ) indicates that the hexapeptide built of (3 R ,4 S )‐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 β ‐ and γ ‐amino acids, which carry heteroatoms on their backbones is discussed ( Fig. 1 ). Positions on the γ ‐peptidic 2.6 14 helix are identified at which non‐H‐atoms are `allowed' ( Fig. 2 ).