Preparation and Use of Benzhydrylamine Polymers in Peptide Synthesis. II. Synthesis of Thyrotropin Releasing Hormone, Thyrocalcitonin 26-32, and Eledoisin

Three procedures have been developed for the synthesis of a benzhydrylamine polymer for the preparation of C-terminal amide peptides by solid-phase synthesis. From a common keto intermediate, prepared by acylation of polysterene-1% divinylbenzene with benzoyl chloride, the desired product can be obtained directly by the Leukart reaction, by reduction of an oxime intermediate, or by ammonolysis of the benzhydryl bromide intermediate. The application of this support to the syntheses of the wide range of peptide hormones possessing a C-terminal amide is illustrated by the syntheses of TRH, the C-terminal heptapeptide fragment of thyrocalcitonin, and the endecapeptide, eledoisin.