Spirolactams as conformationally restricted pseudopeptides: synthesis and conformational analysis.
The synthesis of 1-(tert-butoxycarbonyl)-7-[1-(tert-butoxycarbonyl)-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.5]decanes (S,S)-1a and (S,R)-1b is described. Derivatives 17a,b and 19a are prepared for use in peptide synthesis as constrained surrogates of the Pro-Leu and Gly-Leu dipeptides. The Ac-[Gly-Leu]-Met-NH(2) derivatives (S,S,S)-2a and (S,R,S)-2b, with the tripeptidic C-terminal region present in tachykinins, are also synthesized. Conformational analyses of these tripetide analogues by NMR experiments and molecular modeling calculations show that both (S,S,S)-2a and (S,R,S)-2b epimers are gamma-turn/distorted type II beta-turn mimetics.
Fernández
M Montserrat
MM
Departament de Química Orgànica, Facultat de Química, Universitat de Barcelona, c/Martí i Franquès, Spain.
Diez
Anna
A
Rubiralta
Mario
M
Montenegro
Elvira
E
Casamitjana
Núria
N
Kogan
Marcelo J
MJ
Giralt
Ernest
E
D006860:Hydrogen Bonding; D007769:Lactams / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013696:Temperature; D013816:Thermodynamics
D007769:Lactams; D010455:Peptides