Facile and E-Selective Intramolecular Ring-Closing Metathesis Reactions in 310-Helical Peptides: A 3D Structural Study
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- 作者：Amie K. Boal ; Ivan Guryanov ; Alessandro Moretto ; Marco Crisma ; Erica L. Lanni ; Claudio Toniolo ; Robert H. Grubbs ; Daniel J. O'Leary
- 刊名：Journal of the American Chemical Society
- 出版年：2007
- 出版时间：June 6, 2007
- 年：2007
- 卷：129
- 期：22
- 页码：6986 - 6987
- 全文大小：93K
- 年卷期：v.129,no.22(June 6, 2007)
- ISSN：1520-5126
文摘
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, 
-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.
-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.