Direct Solid Phase Synthesis of Biologically Active Peptide Alcohols

New procedures have been developed for the synthesis of peptide alcohols, such as octreotide conjugates, fragment of gramicidin, and fragment of Trichorzianines in high yield using dihydropyran-2-carboxylic acid as a bifunctional linker to anchor Fmoc-threoninol(Bu^t), Fmoc-glycinol, and Fmoc-phenylalaninol onto amine-resins. The linker is stable during peptide elongation as evidenced by a high yield at each coupling step. The octreotide disulfide bonds were formed on-resin by incubating the elongated octreotide/resin with Tl(TFA)₃/DMF at 0 °C for 1 hour. Tl(TFA)₃/DMF is sufficiently mild that the protecting group and the linker remain intact and allow further the direct coupling of conjugates to octreotide using an autosynthesizer.