Folded biomimetic oligomers for enantioselective catalysis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 106; no. 33; pp. 13679 - 13684
• Main Authors: Maayan, Galia, Ward, Michael D, Kirshenbaum, Kent
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 18.08.2009; National Acad Sciences
• Subjects: Active sites; Alcohols; Benzyl Alcohols - chemistry; Biochemistry; Biomimetics; Biopolymers; Catalysis; Catalysts; Chromatography, Gas - methods; Circular Dichroism; Cyclic N-Oxides - chemistry; Deoxyribonucleic acid; DNA; Kinetics; Models, Chemical; Models, Molecular; Molecular Conformation; Oligomers; Oxidation; Oxygen - chemistry; Peptides - chemistry; Physical Sciences; Protein Structure, Tertiary; Proteins; Reaction kinetics; Resins; Ribonucleic acid; RNA; Scaffolds; Solvents; Stereoisomerism; Temperature
• DOI: 10.1073/pnas.0903187106
• ISSN: 0027-8424

Many naturally occurring biopolymers (i.e., proteins, RNA, DNA) owe their unique properties to their well-defined three-dimensional structures. These attributes have inspired the design and synthesis of folded architectures with functions ranging from molecular recognition to asymmetric catalysis. Among these are synthetic oligomeric peptide ("foldamer") mimics, which can display conformational ordering at short chain lengths. Foldamers, however, have not been explored as platforms for asymmetric catalysis. This report describes a library of synthetic helical "peptoid" oligomers that enable enantioselective transformations at an embedded achiral catalytic center, as illustrated by the oxidative kinetic resolution of 1-phenylethanol. In an investigation aimed at elucidating key structure-function relationships, we have discovered that the enantioselectivity of the catalytic peptoids depends on the handedness of the asymmetric environment derived from the helical scaffold, the position of the catalytic center along the peptoid backbone, and the degree of conformational ordering of the peptoid scaffold. The transfer of chiral information from a folded scaffold can enable the use of a diverse assortment of embedded achiral catalytic centers, promising a generation of synthetic foldamer catalysts for enantioselective transformations that can be performed under a broad range of reaction environments.