Synthesis of 2,2-disubstituted pyrrolidine-4-carboxylic acid derivatives and their incorporation into beta-peptide oligomers.
[reaction: see text] We have recently shown that members of a new class of beta-peptides, containing 2,2-disubstituted pyrrolidine-4-carboxylic acid residues, display discrete conformational preferences despite the impossibility of internal hydrogen bonding (Huck et al. J. Am. Chem. Soc. 2003, 125, 9035). Here we describe the synthesis of a variety of 2,2-disubstituted pyrrolidine-4-carboxylic derivatives that bear a diverse set of side chains and protecting groups suitable for oligomer synthesis. In addition, we discuss coupling methods for construction of oligomers in solution and on solid phase. Non-hydrogen bonded foldamers such as those generated from 2,2-disubstituted pyrrolidine-4-carboxylic acids may be useful in biomedical applications because the low intrinsic polarity of their backbones may promote bioavailability.
Huck
Bayard R
BR
Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53706, USA.
Gellman
Samuel H
SH
D002264:Carboxylic Acids / Q000138:chemical synthesis*; D020650:Combinatorial Chemistry Techniques; D019281:Dimerization; D006860:Hydrogen Bonding; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011759:Pyrrolidines / Q000138:chemical synthesis*
D002264:Carboxylic Acids; D009842:Oligopeptides; D011759:Pyrrolidines; C032519:pyrrolidine