Depsipeptide Methodology for Solid-Phase Peptide Synthesis: Circumventing Side Reactions and Development of an Automated Technique via Depsidipeptide Units
| Autor: | Louis A. Carpino, Calin Dan Sferdean, Irene Coin, Michael Beyermann, Michael Bienert, Eberhard Krause, Rudolf Dolling |
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| Rok vydání: | 2006 |
| Předmět: |
Depsipeptide
Pseudoproline Molecular Structure Stereochemistry Molecular Sequence Data Organic Chemistry Side reaction Diketopiperazines Automated technique Appropriate use Amides Combinatorial chemistry Chemical synthesis Piperazines chemistry.chemical_compound chemistry Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Peptide synthesis Peptides Protecting group Chromatography High Pressure Liquid |
| Zdroj: | The Journal of Organic Chemistry. 71:6171-6177 |
| ISSN: | 1520-6904 0022-3263 |
| Popis: | The depsipeptide technique is a recently developed method for peptide synthesis which is applicable to difficult sequences when the synthetic difficulty arises because of aggregation phenomena. In the present work, application of the depsipeptide method to extremely difficult sequences has been demonstrated and a serious side reaction involving diketopiperazine formation uncovered and subsequently avoided by the appropriate use of the Bsmoc protecting group. Many other aspects of the technique have been investigated, such as the stability of the depsi units during assembly and workup procedures, the completeness of the O-acylation step, the occurrence of epimerization of the amino acid activated during O-acylation, and the nature of side products formed. In addition, the method was modified so as to allow for completely automated syntheses of long-chain depsipeptides without the need for any interruption by manual esterification procedures. Finally, the synthesis efficiency of the new depsipeptide technique was shown to be comparable to that of the well-known pseudoproline technique. |
| Databáze: | OpenAIRE |
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