Z-Selective olefin metathesis on peptides: investigation of side-chain influence, preorganization, and guidelines in substrate selection.

摘要: Olefin metathesis has emerged as a promising strategy for modulating the stability and activity of biologically relevant compounds; however, ability to control olefin geometry in product remains challenge. Recent advances design cyclometalated ruthenium catalysts led new strategies achieving such with high fidelity Z selectivity, but scope limitations these on substrates bearing multiple functionalities, including peptides, remained unexplored. Herein, we report an assessment various factors that contribute both productive nonproductive Z-selective peptides. The influence sterics, side-chain identity, preorganization through peptide secondary structure are explored by homodimerization, cross metathesis, ring-closing metathesis. Our results indicate amino acid side chain identity profoundly criteria set forth conversion selectivity highlighted diverse substrates. principles outlined this important not only expanding peptides also applying stereoselective general synthetic endeavors.