Soluble Non-Crosslinked Poly(Norbornene) Supports for Peptide Synthesis with Minimal Reagents

Nimmashetti Naganna and Nandita Madhavan, J. Org. Chem., Just Accepted Manuscript  DOI: 10.1021/jo502197n  Publication Date (Web): November 5, 2014                  Copyright © 2014 American Chemical Society

 Solid phase peptide synthesis has been an attractive method for synthesizing peptides as it is quick and the peptide synthesis can be automated. The heterogeneous reaction medium in solid phase peptide synthesis necessitates the use of large equivalents of reagents to drive the reactions to completion. Peptide synthesis using soluble, yet isolable, supports is an attractive alternative to solid phase peptide synthesis. Reported herein, is a soluble poly(norbornene) derived support containing multiple attachment sites for high loading capacities and solubilizing oligoether/alkyl groups. The Ala-attached support has been used to synthesize tri- to octapeptides in 28 to 97% yields using only 1.2 equivalents of amino acids and coupling reagents. The acyclic hexapeptide precursor to natural product Segatalin A was synthesized in 41% yield on the support using one eighth the equivalents of coupling reagents as compared to reported procedures. The support could be recovered in up to 98% yield afterpeptide synthesis and the recovered support was utilized to synthesize tetrapeptides that contain amino acids other than Ala at the C-terminus in ca. 80% yields.