Anisole → HCID 86739975, compound

Participants

Reaction Steps

After conventional solid-phase assembly beginning with 1 mmole of Boc-Phe-Merrifield resin (1% cross-linked), the protected peptide hydrazide, H-D-Trp-Lys(Cl-Z)-Thr(Bzl)-Pro-Phe-NHNH2, is cleaved from the support by treatment with hydrazine in methanol and isolated by a procedure described by D. F. Veber et al., Proceedings of the National Academy of Science, U.S.A., 75: 2636-2640, (1978). Without further purification, the hydrazide is converted to the azide, neutralized with triethylamine, and cyclized in DMF solution to yield the protected ninhydrin negative material, cyclo[Pro-Phe-D-Trp-Lys-(Cl-Z)-Thr(Bzl)]. When this protected ninhydrin negative material is hydrogenated at atmospheric pressure and room temperature over 10% Pd on charcoal, the compound, cyclo[Pro-Phe-D-Trp-Lys-Thr(Bzl)], is formed and found to be a very effective somatostatin antagonist. When, however, the protected crude ninhydrin negative material is deprotected by treatment with HF-anisole under standard conditions, as described by G. T. Engberg et al., Nature, 293: 222-223, (1981), and purified by preparative HPLC eluting with 10-55% gradient of CH3CN in 20% AcOH, the reaction yields the pure peptide, cyclo(Pro-Phe-D-Trp-Lys-Thr), which has somatostatin antagonist activity.

Provenance & Evidence