Cyclization studies with tetra- and pentapeptide sequences corresponding to beta-casomorphins

The tetrapeptide Boc-D-Orn-Phe-D-Pro-Gly-OH and the pentapeptide sequence Boc-Tyr(tBu)-D-Orn-Phe-D-Pro-Gly-OH were used to study the influence of different coupling reagents on the yield and purity of these model peptides. The simple structure prevented racemization and cyclodimerization and facilitated the ring formation. The most favorable effects on yield and purity were obtained in both reactions using diphenyl-phosphoryl azide (DPPA) and norborn-5-ene-2,3-dicarboximidodiphenylphosphate (NDPP), while the cyclizations with the powerful activating reagents benzotriazol-1-yl-oxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP) and 2-(1-H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) with the exception of the cyclopentapeptide reaction with HBTU/4-dimethylaminopyridine gave unsatisfactory results.