Quantitative Modeling of Bis(pyridine)silver(I) Permanganate Oxidation of Hydantoin Derivatives: Guidelines for Predicting the Site of Oxidation in Complex Substrates
| Autor: | Amanda J. Bischoff, Mohammad Movassaghi, Zachary L. Niemeyer, Brandon M. Nelson, Matthew S. Sigman |
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| Rok vydání: | 2017 |
| Předmět: |
010405 organic chemistry
Hydantoins Permanganate Iminium Hydantoin Diketopiperazines General Chemistry 010402 general chemistry 01 natural sciences Biochemistry Redox Combinatorial chemistry Article Catalysis 0104 chemical sciences Hydroxylation chemistry.chemical_compound Colloid and Surface Chemistry chemistry Nucleophile Pyridine Organic chemistry Oxidation-Reduction |
| Zdroj: | Journal of the American Chemical Society. 139:15539-15547 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.7b09541 |
| Popis: | The bis(pyridine)silver (I) permanganate promoted hydroxylation of diketopiperazines has served as a pivotal transformation in the synthesis of complex epipolythiodiketopiperazine alkaloids. This late-stage C–H oxidation chemistry is strategically critical to access N-acyl iminium ion intermediates necessary for nucleophilic thiolation of advanced diketopiperazines en route to potent epipolythiodiketopiperazine anticancer compounds. In this study, we develop an informative mathematical model using hydantoin derivatives as a training set of substrates by relating the relative rates of oxidation to various calculated molecular descriptors. The model prioritizes Hammett values and percent buried volume as key contributing factors in the hydantoin series while correctly predicting the experimentally observed oxidation sites in various complex diketopiperazine case studies. Thus, a method is presented by which to use simplified training molecules and resulting correlations to explain and predict reaction behavior for more complex substrates. |
| Databáze: | OpenAIRE |
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