Cyclische Peptide. VI. Peptidchlorid‐hydrochloride als energiereiche Derivate zur Darstellung cyclischer Peptide

Abstract

Es wird eine neue Methode zur Peptidcyclisierung mit Hilfe von Peptidchlorid‐hydrochloriden als energiereichen Derivaten nach dem Zieglerschen Verdünnungsprinzip beschrieben. Nach Ausarbeitung günstiger Ringschlußbedingungen konnten Cyclohexaglycyl in 11proz. und Cyclo‐di‐ε‐aminocaproyl in 37proz. Ausbeute erhalten werden. Die Darstellung analysenreiner Peptidchlorid‐hydrochloride wird eingehend behandelt. Für die Gewinnung höherer Glycinpeptide erwies sich der Weg über die Carbobenzoxyderivate mit nachfolgender Abspaltung der Schutzgruppe mit HBr/Eisessig vorteilhafter als die Aminierung der Chloracetylpeptide.

Fibrin-stabilizing factor inhibitors. 5. Primary amines related to monotosylcadaverine

“…TV-(5-Aminopentyl)-p-methylbenzamide (7). Compd 6 (0.50 g, 2.3 mmoles) was hydrogenated over Pt02 as described for 4.…”

Methods of Peptide Synthesis

“…Systematic studies on the effect of dilution, which is known to be important in this field, have been made by Rothe and coworkers [152], albeit on a "degenerate" model. Cyclization of E-aminocaproyl-Eaminocaproyl chloride, which was set free from its hydrochloride by triethylamine in dimethylformamide, gave the yields shown in Table 1 after two hours' reaction.…”

Formation of oligomers on N-acylation of tripeptides. Proton magnetic resonance spectra of the peptides

“…For both II and Via the phenylalanyl ß protons are sufficiently nonequivalent in dimethyl sulfoxide (0.2 ppm) and in water (0.08 ppm) to permit analysis of their spin-spin splitting patterns. The geminal coupling constant is 14 Hz, but the significant observation is that in each case the a proton is coupled to the higher field ß proton by about 10 Hz, and to the lower field ß proton by about 4 Hz. These -ß couplings indicate that the favored -ß rotamer for this residue is one with a trans arrangement of vicinal protons.…”

“…The tripeptide glycyclglycylglycine can be N acylated with benzyloxycarbonyl chloride in aqueous alkali; a 65% yield of N-acyltripeptide has reported. 14 We have repeated this acylation without detecting higher polyglycine derivatives chromatographically.19 Thus it appears that N acylation is favored for glycylglycylglycine, but, considering the extent of oligomerization described above, tripeptides L-Phe-GIy-L-Leu and L-Leu-L-Phe-L-Ala must undergo predominant carboxyl acylation.…”