Total Synthesis of Leupyrrins A1and B1, Highly Potent Antifungal Agents from the MyxobacteriumSorangium cellulosum
| Autor: | Maoqun Tian, Tongtong Wang, Thomas Debnar, Sebastian Thiede, Daniel Herkommer, Michael Schrempp, Dirk Menche, Paul R. Wosniok |
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| Rok vydání: | 2016 |
| Předmět: |
chemistry.chemical_classification
biology 010405 organic chemistry Lactol Organic Chemistry Regioselectivity Total synthesis General Chemistry 010402 general chemistry biology.organism_classification 01 natural sciences Combinatorial chemistry Aldehyde Catalysis 0104 chemical sciences chemistry.chemical_compound chemistry Cascade reaction Amide Pyrrole Sorangium cellulosum |
| Zdroj: | Chemistry - A European Journal. 23:3300-3320 |
| ISSN: | 0947-6539 |
| DOI: | 10.1002/chem.201604445 |
| Popis: | Full details on the design, elaboration, and application of efficient strategies for the high-yielding total syntheses of leupyrrins A1 and B1 , unique antifungal agents from the myxobacterium Sorangium cellulosum, are reported. A sequential zirconocene-mediated diyne-cyclization, and regioselective opening of the zirconacyclopentadiene intermediate enabled a concise entry into the unique dihydrofuran fragment, whereas another domino reaction was developed for the butyrolactone involving a one-pot lactol opening, stereoselective aldehyde addition and in situ lactonization. Furthermore, an innovative sp2 -sp3 -cross-coupling for pyrrole functionalization and an optimized HATU-mediated amide coupling protocol of two elaborate fragments were established. In addition, an unusual protective group strategy, involving a Teoc-acetonide protected amine in combination with tert-butyl and acetate esters, was successfully elaborated. These tactics and strategies are generally useful and may be also applied in the synthesis of other functionalized compounds. It is expected that the material which was obtained by these total syntheses will enable the further exploration of the biological profile of these potent antifungal agents. |
| Databáze: | OpenAIRE |
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