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978-3-8439-1909-8, Reihe Organische Chemie
Photoarylierung von Aminosäuren und Peptiden mit 2-Azidobenzimidazol
201 Seiten, Dissertation Technische Universität Braunschweig (2014), Softcover, A5
The irradiation of 2-azido-1-(4-fluorobenzyl)-1H-benzo[d]imidazole revealed a novel photoarylation of acetic acid to the arylester 2-amino-1-(4-fluorobenzyl)-1H-benzo[d]imidazolo-6-yl-acetate. After irradiation the azidobenzimidazole dissociates to nitrogen and benzimidazolylnitrene, which undergoes ringopening to a N cyanodiazaxylylene. The N-cyanodiazaxylylene is activated in the 6-position via protonation and arylates nucleophiles with recovery of the aromatic system. The photoarylation with azidobenzimidazole under acidic conditions was applied to various Brønsted-acids with sufficiently low pKa value.
The carboxylic side chain of C-terminal benzylated Boc-Asp-OBn and the C-terminal carboxylic functions of N-Boc-protected Gly, Ala, Val, Leu, Phe, Ser and Tyr were successfully arylated. The arylation of the peptides Boc-Ile-Ser-OH and Boc-Asn-Ile-Ser-OH proceeded in higher yields than the arylation of the amino acids. No defined products were found after photoarylation of a tryptophan containing tripeptide or Boc-tryptophan as amino acid. Conversion of the arylester of N-Boc-protected His, Cys and Met with pyrrolidine to the pyrrolidinamides and hydroxybenzimidazole indirectly prooved their arylation. During the photoarylation of cystine and methionine unexpected sideproducts were formed. The nonapeptide H-Ser-Pro-Ser-Tyr-Val-Tyr-His-Gln-Phe-OH was arylated at the phenolic tyrosin side chain instead of the terminal carboxylic function. The position of the label was determined by collision induced dissociation via ESI-MS/MS. Human insulin was successfully arylated in the presence of 2-azidobenzimidazole. Yet the location of the label remains unknown.
The racemic amino acid β-(2-azido-1-benzoimidazolyl)-alanine was synthesized to demonstrate the use of 2-azidobenzimidazole as partial structure of photoreactive amino acids. The photoactivation of the amino acid was confirmed by arylation of acetic acid. A hemiasterlin analogon with β-(2-azido-1-benzoimidazolyl)-alanine as partial structure was synthesized by peptide coupling, however against expectation it showes low cytotoxic activity.