Neue Methoden zur Herstellung von Carbonsäure‐arylestern. Über aktivierte Ester VIII

Abstract

Carbonsaureester, welche in der Alkoholkomponente an geeigneter Stelle negative Substituenten tragen, besitzen Eigenschaften von Acylierungsmitteln. Solche sogenannte ,,aktivierte Ester" eignen sich besonders zur Synthese von Peptiden.Wahrenddem der Einfluss des negativen Substituenten auf die Carboxylgruppe in den a l i p h a t i s c h e n a,ktivierten Estern wesentlich induktiver Natur sein durfte2), ist in den in 0 -oder p-Stellung negativ substituierten a r o m a t i s c h e n aktivierten Estern wahrscheinlich ein elektromerer Mechanismus wirksam (Schema 1, a und b) :Infolgedessen ist bei negativ substituierten aromatischen Estern eine besonders starke Aktivierung zu erwarten.Diese Erwartung wurde durch Untersuchungen von Boddnnsxky und Mitarbeitern3) bestatigt. Trotzdem haben sktivierte Arylester bisher wenig praktische Verwendung gefunden. Das liegt zur Hauptsache an ihrer relativ schweren Zuganglichkeit. I m Gegensatz zu aktivierten Alkylestern, welche direkt aus Carbonsawen und substituierten Halogenalkylen gewonnen werden konnen (Schema 2, a), mussten aktivierte Arylester auf dem Umwege iiber Saureanhydride oder -halogenide hergestellt werden (z. B. Schema 2, b):

Synthesis of Cyclic Peptides

“…Conversion is carried out commonly by reaction of the peptide acid with p-nitrophenyl sulfite (14) or pnitrophenyl trifluoroacetate (1 5, 16). Conversion is carried out commonly by reaction of the peptide acid with p-nitrophenyl sulfite (14) or pnitrophenyl trifluoroacetate (1 5, 16).…”

Methods of Peptide Synthesis

“…For example, carbobenzoxyamino acids are first treated with aminoacyl-p-nitrophenols by means of the anhydride method or dicyclohexylcarbodiimide, forming the p-nitrophenyl esters of the carbobenzoxy-dipeptides, which react further without isolation with another amino ester. The p-nitrophenyl esters may be obtained from acylamino acids and the corresponding sulfite OS(0Ar)Z or phosphite P(OAr)3 [94] as well as from their components using dicyclohexylcarbodiimide [95-971. Heating of the acids with di-p-nitrophenyl carbonate OC(OAr)2 [98] is also successful. Numerous other phenyl esters have also been made by the sulfite and phosphite methods [94].…”

“…The p-nitrophenyl esters may be obtained from acylamino acids and the corresponding sulfite OS(0Ar)Z or phosphite P(OAr)3 [94] as well as from their components using dicyclohexylcarbodiimide [95-971. Heating of the acids with di-p-nitrophenyl carbonate OC(OAr)2 [98] is also successful. Numerous other phenyl esters have also been made by the sulfite and phosphite methods [94]. The p-methylsulfonylphenyl esters have recently been used [99] on account of the resistance of this group later on, when the N-protecting group has to be split off by catalytic hydrogenation.…”

Bis(p-nitrophenyl) Sulfite

“…The activated ester is prepared by the reaction of a peptide or N-protected amino acid in pyridine with bis(p-nitrophenyl) sulfite (eq 1). (1) Some racemization has been observed where the amino acid is not a glycine or proline residue. An example of the use of this reagent is in the preparation of a cyclic peptide (eq 2).…”