Ferrier Carbocyclization-Mediated Synthesis of Enantiopure Azido Inositol Analogues
| Autor: | Benjamin M. Swarts, Alex P. Ausmus, Nicholas Banahene, Sarah R. Rundell, Krestina M. Bednarz, Maxwell Hogue, Justin L. Snyder |
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| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Azides 010405 organic chemistry Stereochemistry Glycoconjugate Organic Chemistry Leaving group 010402 general chemistry 01 natural sciences 0104 chemical sciences chemistry.chemical_compound Ferrier carbocyclization Enantiopure drug Glucosides chemistry Inositol Azide Protecting group Glycoconjugates |
| Zdroj: | The Journal of Organic Chemistry. 85:3182-3191 |
| ISSN: | 1520-6904 0022-3263 |
| Popis: | Azide-modified inositol (InoAz) analogues are valuable as inhibitors and have shown promise as metabolic chemical reporters (MCRs) for labeling inositol-containing glycoconjugates in eukaryotic cells and potentially in mycobacteria, but the synthesis of enantiomerically pure InoAz analogues via traditional approaches is challenging. As a complementary route, here we investigated the application of the Ferrier carbocyclization reaction to the synthesis of enantiopure InoAz analogues starting from readily available azido glucosides. Using this approach combined with a para-methoxybenzyl protecting group strategy, 3-azido-3-deoxy- and 4-azido-4-deoxy-d-myo-inositol were efficiently synthesized. 5-Azido-5-deoxy-d-myo-inositol was inaccessible due to an unusual β-elimination reaction, wherein the azide anion acted as the leaving group. The reported strategy is expected to facilitate continued development of synthetic InoAz analogues as inhibitors or MCRs of inositol-containing glycoconjugates in eukaryotic and mycobacterial systems. |
| Databáze: | OpenAIRE |
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