Facile and E-Selective Intramolecular Ring-Closing Metathesis Reactions in 310-Helical Peptides: A 3D Structural Study
Citations Over TimeTop 10% of 2007 papers
Abstract
The ring-closing metathesis reaction can be used to cross-link allylated serine residues situated at the i and i + 3 positions in 310-helical peptides containing the helicogenic amino acid, α-aminoisobutyric acid (Aib). An octapeptide with the sequence Boc-Aib-Aib-Aib-Ser(Al)-Aib-Aib-Ser(Al)-Aib-OMe was found to undergo a facile and >20:1 E-selective ring-closing metathesis (RCM) reaction catalyzed by the Grubbs second-generation catalyst to yield an 18-membered macrocycle. The formation of this cross-link does not significantly disturb the peptide's native 310-helicity, as judged by an X-ray diffraction study of the acyclic diene, the E-olefin RCM product, and its hydrogenated derivative. A heptapeptide system with the sequence Boc-Val-Ser(Al)-Leu-Aib-Ser(Al)-Val-Leu-OMe also underwent an efficient RCM reaction, albeit with diminished E-selectivity. It is apparent from these studies that a minimal, RCM-derived, macrocyclic constraint can be readily incorporated into 310-helical peptides.
Related Papers
- → An Imine Addition/Ring-Closing Metathesis Approach to the Spirocyclic Core of Halichlorine and Pinnaic Acid(2000)147 cited
- → Total Synthesis of (+)‐Migrastatin(2006)27 cited
- → 4902764 Polymeric sulfide mineral depressants(1990)2 cited
- → Metathesis Reactions in Solid‐Phase Organic Synthesis(2010)2 cited
- → Nanoparticulate gold oxidation catalyst(2003)