Die Synthese von β,β-Diaryl-α-Aminosäurehybriden zur Modifikation von Peptidhormonen
Die vorliegende Arbeit befasst sich mit der Generierung eines synthetischen Zugangs zu α-Aminosäurehybriden, die aus codierten α-Aminosäuren gebildet wurden. Ausgehend von Alanin wurde durch die dirigierte C–H Aktivierung die β-Position sequentiell modifiziert, sodass neben einigen weiteren Deriv...
المؤلف الرئيسي: | |
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مؤلفون آخرون: | |
التنسيق: | Dissertation |
اللغة: | الألمانية |
منشور في: |
Philipps-Universität Marburg
2020
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الموضوعات: | |
الوصول للمادة أونلاين: | PDF النص الكامل |
الوسوم: |
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This work covers the development of a synthetic access to α-amino acid hybrids composed of encoded α-amino acids. The sequential modification of the β-position of alanine using directed C–H activation mainly gave rise to hybrids of tryptophan and phenylalanin, among other derivatives. The anti-periplanar χ-space arrangement of the amino acid hybrids was defined through β-disubstitution, which allowed the pre-synthetic spacial planning of substituent orientation. Furthermore, new concepts were introduced to enable the mild and selective cleavage of amide-based, C-terminal directing groups. Using this new method, non-planar amides could successfully be used in unusual transamidation reactions and were characterized by crystallographic and in silico methods. Moreover, the altered amide geometry facilitated the C-terminal derivatization of the α- amino acid hybrids. In conclusion, the synthetic concepts of C–H activation were improved and the chemistry of amidebased directing groups was revisited to access gram-scale quantities of novel α-amino acid hybrids. These ready-to-use building blocks for automated peptide synthesis enabled the formation of tailored peptide hormones with distinct structural changes and unique biological profiles.