The Arndt-Eistert Reaction in Peptide Chemistry: A Facile Access to Homopeptides
Joachim Podlech, Dieter Seebach*
*Laboratory of Organic Chemistry, Wolfgang-Paulistrasse 10, HCI H331, 8093
Zuerich, Switzerland, Email: seebach
org.chem.ethz.ch
J. Podlech, D. Seebach, Angew. Chem. Int. Ed., 1995, 34, 471-472.
DOI: 10.1002/anie.199504711
Abstract
The chain extension of carboxylic acids developed by Arndt and Eistert was applied to the construction of peptides containing β-amino acids. The method may be used for the generation of new types of peptide-containing combinatorial libraries.
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Details
The Arndt-Eistert reaction in peptide chemistry, as discussed by Joachim Podlech and Dieter Seebach, focuses on the synthesis of homopeptides by incorporating β-amino acids. β-Amino acids, though less common than α-amino acids, are significant in the creation of modified peptides and β-lactam antibiotics. The authors describe a novel approach that combines the generation of β-amino acid moieties with peptide coupling steps. The process involves the chain extension of carboxylic acids using the Arndt-Eistert reaction.
The method starts with the activation of Z-protected alanine using ethyl chlorocarbonate, followed by reaction with diazomethane to form diazoketones. These diazoketones are then treated with silver benzoate and a nucleophile, such as valine benzyl ester, to yield homopeptides. The reaction proceeds with good yields, and the products are characterized by mass spectrometry, elemental analysis, and optical rotation.
The intermediate ketene formed in the reaction is not stable and instead forms a dihydrooxazinone, which reacts with nucleophiles to produce the desired homopeptides. This method allows for the insertion of β-amino acids at any stage of peptide synthesis and can be used to create new peptide-containing combinatorial libraries.
Key Words
Arndt-Eistert synthesis, β-amino acids, α-diazoketones, dihydrooxazinones, homopeptides, peptide analogues
ID: J06-Y1995-540
