Synthesis of conformationally restricted amino acids, peptides, and peptidomimetics by catalytic ring closing metathesis

Abstract

A method for synthesizing conformationally restricted amino acids, peptides, and peptidomimetics by ring closing metathesis. The method includes the steps of synthesizing a peptide precursor containing first and second unsaturated C--C bonds and contacting the peptide precursor with a RCM catalyst to yield a conformationally restricted peptide. Suitable peptide precursors may contain two or more unsaturated C--C bonds. These bonds may be olefinic bonds and may be contained in first and second alkenyl groups which may be allyl groups. The RCM catalyst may be a Ruthenium or Osmium carbene complex catalyst and more specifically, a Ruthenium or Osmium carbene complex catalyst that includes a Ruthenium or Osmium metal center that is in a +2 oxidation state, has an electron count of 16, and is pentacoordinated. The method may be carried out using solid-phase-peptide-synthesis techniques. In this embodiment, the precursor, which is anchored to a solid support, is contacted with a RCM catalyst and the product is then cleaved from the solid support to yield a conformationally restricted peptide.

Dependencies are inferred from the claim text.