Hydrazinverbindungen als Heterobestandteile in Peptiden. XVI. Synthese von 9‐Hydrazinoessigsäure‐, 9‐Azaglycin‐ und 5‐α‐Azaasparagin‐Oxytocin

Abstract

Zur Untersuchung des Einflusses von Modifikationen der Polyamidkette auf die Konformation und die biologische Aktivität des Oxytocins wurden 9‐NHGly‐OT‐, 9‐Azgly‐OT und 5‐Azasn‐OT synthetisiert. Zur Synthese des C‐terminalen Hexapeptides wurden aktivierte Tripeptidester eingesetzt. Die 3 + 6‐Azidsynthese erwies sich auch hier einer 6 + 3‐Synthese überlegen.

X‐ray structures of aza‐proline‐containing peptides

“…After the pioneering works of Hess et al (4) and Gante & Lautsch ( 5 ) in the aza-peptides field, other pseudopeptides including various aza-residues, denoted by AzXaa in the following, have been prepared and studied mainly from a biological point of view. They have been introduced in analogues of angiotensin I1 (4,6), oxytocin (7), eledoisin (8-lo), luliberin (1 1-16), somatostatin (17), enkephalin (18,19) and in various protease inhibitors (20)(21)(22)(23)(24)(25)(26). Many aza-surrogates of the proteinaceous amino acids have been described, including those bearing an aliphatic side-chain (27,28) as Abbreviations: Ac, acetyl; AzAla, aza-analogue of alanine; AzAsn, aza-analogue of asparagine; AzAsp, aza-analogue of aspanic acid; AzPro, aza-analogue of proline; AzXaa, aza-analogue of an amino acid residue; Boc, terr-butyloxycarbonyl; Me, methyl; iPr, isopropyl; Piv, pivalyl; Z, benzyloxycarbonyl.…”

Azapeptides as Pharmacological Agents

“…[AAsn 5 ]-oxytocin was inactive when tested on the rat uterus, while [AGly 9 ]-oxytocin was 1.5 times more active than the natural hormone [35,36].…”

“…The aza analogue of eledoisin, [AAsn 5 ]-eledoisin 4-11, was 3-4 times more potent in isolated ileal sections and in raising blood pressure than the non-aza analogue, and its action was also prolonged [35][36][37][38].…”

Synthesis and Chemistry of α‐Hydrazino Acids

“…The presence of two nitrogen atoms in a-hydrazino acids led Niedrich to connect the peptidic chain either on the N 2 atom to give a pseudopeptide that he named a hydrazinopeptide or on the N 1 atom to give a pseudopeptide that he named an aminopeptide (Figure 2.5) [43][44][45][46][47][48][49][50][51][52][53][54][55]. The presence of two nitrogen atoms in a-hydrazino acids led Niedrich to connect the peptidic chain either on the N 2 atom to give a pseudopeptide that he named a hydrazinopeptide or on the N 1 atom to give a pseudopeptide that he named an aminopeptide (Figure 2.5) [43][44][45][46][47][48][49][50][51][52][53][54][55].…”