Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis
| العنوان: | Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis |
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| المؤلفون: | Dhineshkumar Jayaraman, Jeffrey Buter, Nabil Tahiri, D. Branch Moody, Martin D. Witte, Adriaan J. Minnaard, Tonatiuh A. Ocampo, Peter Fodran, Ildiko Van Rhijn |
| المساهمون: | Chemical Biology 2, Synthetic Organic Chemistry |
| المصدر: | Angewandte Chemie (International ed. in English), 59(19), 7555-7560. WILEY-V C H VERLAG GMBH Angewandte Chemie (International Ed. in English) |
| بيانات النشر: | Wiley, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Antigenicity, T-Lymphocytes, CD1b, cross coupling, Lymphocyte Activation, 010402 general chemistry, 01 natural sciences, Catalysis, Mycolic acid, Antigens, CD1, Mycobacterium tuberculosis, chemistry.chemical_compound, Antigen, mycolic acid, Total Synthesis, Moiety, Research Articles, chemistry.chemical_classification, Cord factor, biology, 010405 organic chemistry, Cell Membrane, Total synthesis, Esters, Stereoisomerism, General Chemistry, General Medicine, biology.organism_classification, Trehalose, Tumor Necrosis Factor Receptor Superfamily, Member 7, 0104 chemical sciences, Glucose, tuberculosis, Mycolic Acids, chemistry, Biochemistry, Research Article |
| الوصف: | In Mycobacterium tuberculosis, mycolic acids and their glycerol, glucose, and trehalose esters (“cord factor”) form the main part of the mycomembrane. Despite their first isolation almost a century ago, full stereochemical evaluation is lacking, as is a scalable synthesis required for accurate immunological, including vaccination, studies. Herein, we report an efficient, convergent, gram‐scale synthesis of four stereo‐isomers of a mycolic acid and its glucose ester. Binding to the antigen presenting protein CD1b and T cell activation studies are used to confirm the antigenicity of the synthetic material. The absolute stereochemistry of the syn‐methoxy methyl moiety in natural material is evaluated by comparing its optical rotation with that of synthetic material. The total synthesis of four methoxy mycolic acid diastereomers is described. Key steps involve a Suzuki–Fu cross‐coupling, an anti‐selective Abiko–Masamune asymmetric aldol reaction, and an enantioselective Charette cyclopropanation. CD1b‐free mycolic acid tetramer staining experiments clearly favoured one diastereomer over the other three. |
| وصف الملف: | application/pdf |
| تدمد: | 1521-3757 0044-8249 1433-7851 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e065cac8318aff5519e701a135e99076Test https://doi.org/10.1002/ange.202000523Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e065cac8318aff5519e701a135e99076 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15213757 00448249 14337851 |
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