Peptide Syntheses with the N‐PChd Protective Group Synthesis of the Hydrophobic Segment 14–20 L‐Ala‐Leu‐Ile‐Leu‐Leu‐Ala‐Gln of Human Lymphoblastoid Interferon

Abstract

Amino acid esters were transformed in 59 -97% yields into N-(3,5-di-tert-butyl-4-oxo-l-phenyl-2,s-cyclohexadienyl)amino acid esters (N-PChd amino acid esters) 8 via anodic oxidation in the presence of 2,6-di-fert-butyl-4-phenylphenol (la). Hydrolysis of 8 lead to the corresponding N-PChd amino acids 9. The novel PChd protective group is stable towards basic reagents, it can be removed by hydrogenation or acidolysis, and it exhibits good solubilizing properties for oligopeptides in organic solvents. N-PChd amino acids couple without racemization, they are easily prepared and storable, and crystallize readily. -Using conventional methods of peptide synthesis and PChd deprotection with 10-50% trifluoroacetic acid in dichloromethane or catalytic hydrogenation, the heptapeptide HuIFN-a(Ly)l4 -20 L-Ala-Leu-lle-Leu-Leu-Ala-Gln was synthesized in good yield and purity as shown by column and thin layer chromatography, I3C-NMR spectroscopy, chiral phase gas chromatography, and common analytical methods.Peptidsynthesen mittels der N-PChd-Schutzgruppe. -Synthese des hydrophoben Segments 14 -20 L-Ala-1,eu-Ile-Leu-Leu-Ala-Gln des menschlichen Lymphoblrsten-Interferons Aminosaureester wurden durch anodische Oxidation in Gegenwart von 2,6-Di-tert-butyl-4-phenylphenol (1 a) mit 59 -97% Ausbeute in N-(3,5-Di-rert-butyl-4-oxo-l-phenyl-2,S-cyclohe~a-dieny1)aminosaureester (N-PChd-Aminosaureester) 8 umgewandelt. Die Hydrolyse von 8 fuhrte zu den entsprechenden N-PChd-Aminosauren 9. Die neuartige PChd-Schutzgruppe ist gegenuber basischen Reagentien stabil, sie kann hydrierend oder sauer entfernt werden und bewirkt bessere Ldslichkeit von Oligopeptiden in organischen Losungsmitteln. N-PChd-Aminosauren kuppeln ohne Racemisierung, sind leicht herzustellen und haltbar, und sie kristallisieren bereitwillig. -