SOLID-PHASE, SOLUTION, AND SEGMENT CONDENSATION PEPTIDE SYNTHESES INCORPORATING CHROMIUM CARBENE COMPLEX-DERIVED NONPROTEINOGENIC (UNNATURAL) AMINO-ACID FRAGMENTS

Photolysis of optically active chromium aminocarbene complexes in the presence of tripeptide methyl esters gave protected tetrapeptide methyl esters in good yield and with good diastereoselectivity. Photolysis of these same carbene complexes in the presence of Merrifield resin supported amino acids or tripeptides resulted in incorporation of the chromium carbene complex-derived amino acid fragment into the solid-supported peptide. This photochemical methodology could be used iteratively, but it lacked efficiency. The procedure was most effective for segment condensation peptide synthesis. A tripeptide fragment containing two nonproteinogenic amino acids was synthesized by chromium carbene complex photochemistry. This tripeptide was incorporated into a Merrifield resin supported tripeptide, deprotected, and coupled to two more amino acid fragments using classical procedures to produce an octapeptide incorporating the chromium carbene complex-derived amino acid fragment.