Pellicular silicone resins as solid supports for peptide synthesis

Pellicalar si11cone resins were prepared by polymerization of p-bromomethyl phenyl trichlorosilane (I) and 3-(p-chloromethyl phenyl)-1-tridilorosilyl propane (II) on the surface of glass or silica particles. Monctner (I) was synthesized by reaction of p-tolyl magnesium bromide with silicon tetrachloride, follcvzed by radical bromination with N-bromosuccinimide. Monomer (II) was prepared by addition of p-allylbenzyl chloride to trichlorosilane catalyzed by hexachlorcplatinic acid. A tetrapeptide H-Pro-Gly-Phe-Ala-CH was synthesized on the silicone support fran monomer (I) by standard Merrifield procedure. No failure sequences were detected by amino acid analysis and thin layer chranatography. The cleavage of the peptide by HBr-TFA did not proceed to coupletion. The dodecapeptide H-(Phe-Ala)[lowered 6]OH was syntliesized on the support from monomer (II) by the same procedure. Cleavage by HBr-TFA was in this case practically complete. The peptide was analyzed for the presence of failure sequences by partial hydrolysis with 12 N HCl, followed by GC-MS analysis. Finally, pentapeptide H-GlN-GlN-Gly-Gly-Tyr-NH[lowered 2] was prepared on the support fran monaner (II) by column procedure. The peptide was cleaved fran the resin as a methyl ester, by action of triethylamine/methanol. The protected peptide was purified by gel permeation chranatography and amidated with NH[lowered 3] in DMF-MeOH mixture. The Boc-group was cleaved with INHCl/AcOH. The benzyl groups protecting the side chain of tyrosine were cleaved by catalytic hydrogenation over Pd/charcoal.