Oxidative diversification of amino acids and peptides by small-molecule iron catalysis
| Autor: | Thomas J. Osberger, Donald C. Rogness, Antonia F. Stepan, M. Christina White, Jeffrey T. Kohrt |
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| Rok vydání: | 2016 |
| Předmět: |
Macrocyclic Compounds
Proline Stereochemistry Iron Peptide Synthetases Stereoisomerism Oxidative phosphorylation Hydroxylation 010402 general chemistry 01 natural sciences Catalysis Article Amino Acids chemistry.chemical_classification Multidisciplinary Molecular Structure 010405 organic chemistry Small molecule 0104 chemical sciences Amino acid chemistry Biochemistry Peptides Chirality (chemistry) |
| Zdroj: | Nature |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | Secondary metabolites synthesized by nonribosomal peptide synthetases (NRPSs) display diverse and complex topologies and possess an impressive range of biological activities1,2 Much of this diversity derives from a synthetic strategy that entails the oxidation of both the chiral amino acid building blocks and the assembled peptide scaffolds pre-3 and post-assembly2. The vancomycin biosynthetic pathway is an excellent example of the range of oxidative transformations that can be performed by the iron-containing enzymes involved in its biosynthesis.4 However, because of the challenges associated with using such oxidative enzymes to carry out chemical transformations in vitro, chemical syntheses guided by these principles have not been fully realized outside of nature.5 In this manuscript, we report that two small-molecule iron catalysts are capable of facilitating the targeted C—H oxidative modification of amino acids and peptides with preservation of α-center chirality. Oxidation of proline to 5-hydroxyproline furnishes a versatile intermediate that can be transformed to rigid arylated derivatives or flexible linear carboxylic acids, alcohols, olefins, and amines in both monomer and peptide settings. The value of this C—H oxidation strategy is demonstrated in its capacity for generating diversity: four 'chiral pool' amino acids are transformed to twenty-one chiral unnatural amino acids (UAAs) representing seven distinct functional group arrays; late-stage C—H functionalizations of a single proline-containing tripeptide furnish eight tripeptides, each having different UAAs. Additionally, a macrocyclic peptide containing a proline turn element is transformed via late-stage C—H oxidation to one containing a linear UAA. |
| Databáze: | OpenAIRE |
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