A Synthesis of Thyrotropin-Releasing Factor

Abstract

Abstract A procedure is given for the synthesis of thyrotropin-releasing factor (TRF), a tripeptide l-pyrogultamyl-l-histidyl-l-proline amide. Benzyloxycarbonyl(Z)-glutaminyl-histidyl-proline amide (III) is obtained as an intermediate by the coupling of Z-glutamine p-nitrophenyl ester with histidyl-proline amide which is derived from the crystalline Z-dipeptide amide. Deprotection of III and the subsequent cyclization produce TRF in a moderate yield. Compound III and the corresponding Nα-acetyl derivative have little or no TRF activity.