Effects of thionation and fluorination on cis-trans isomerization in tertiary amides: an investigation of N-alkylglycine (peptoid) rotamers

The Journal of Organic Chemistry
Jens Engel-AndreasenChristian A Olsen

Abstract

Peptoids constitute a class of peptidomimetics with potential as protease resistant, biologically active ligands. To harness the full potential of such compounds, however, detailed predictive insight into their propensity to adopt well-defined secondary structures is highly desirable. In this work we present an investigation of the effects of thioamides and/or fluorides in peptoid monomer model systems using chemical synthesis, NMR spectroscopy, and X-ray crystallography. We find that the steric environment surrounding the tertiary amide bonds is the key promoter of conformational preference, and X-ray crystallographic interrogation of our model systems did not suggest the presence of stabilizing n → π* interactions unless the carbonyls were altered electronically by α-halogenation or thioamide formation. In addition to the function as an investigative tool, these two types of modification may thus be utilized as stabilizers of secondary structure in future oligomer designs, such as the cis-amide-based polypeptoid helices that resemble the polyproline type-I helix.

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Citations

Dec 25, 2015·Chemical Reviews·Niklas GangloffRobert Luxenhofer
Jul 16, 2015·Accounts of Chemical Research·Jonas S LaursenChristian A Olsen
Mar 6, 2019·Biopolymers·Ryan K SpencerRonald N Zuckermann
Jun 30, 2016·Biopolymers·Marta De ZottiClaudio Toniolo
Nov 8, 2019·Acta Biomaterialia·Hannah R ReeseStefano Menegatti
Mar 14, 2019·The Journal of Organic Chemistry·Isabelle WellhöferChristian A Olsen
Aug 19, 2020·The Journal of Organic Chemistry·Isabelle WellhöferChristian A Olsen
Aug 25, 2017·Journal of the American Chemical Society·Olivier RoyClaude Taillefumier
Jan 31, 2019·ACS Chemical Biology·Nilkamal MahantaDouglas A Mitchell
Jun 5, 2018·The Journal of Organic Chemistry·Geoffrey DumonteilClaude Taillefumier
Oct 7, 2021·Chemical Communications : Chem Comm·Claudine Nicole HerlanStefan Bräse

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