Spirolactams as Conformationally Restricted Pseudopeptides: Synthesis and Conformational Analysis
- 3 October 2002
- journal article
- research article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 67 (22) , 7587-7599
- https://doi.org/10.1021/jo025999i
Abstract
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-NH2 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 γ-turn/distorted type II β-turn mimetics.Keywords
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