Formal Total Synthesis of the Algal Toxin (−)-Polycavernoside A
| Autor: | Josep Llaveria, Lennart Brewitz, Akira Yada, Alois Fürstner |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
chemistry.chemical_classification
Stereochemistry Chemistry Alkene Jacobsen epoxidation Organic Chemistry Regioselectivity Total synthesis Stereoisomerism Cycloalkyne General Chemistry Alkenes Disaccharides Metathesis Catalysis Biological Factors chemistry.chemical_compound Cyclization Alkynes Alkyne metathesis Macrolides Hydroalkoxylation |
| Zdroj: | Chemistry - A European Journal. 19:4532-4537 |
| ISSN: | 0947-6539 |
| DOI: | 10.1002/chem.201204551 |
| Popis: | A concise and largely catalysis-based approach to the potent algal toxin polycavernoside A (1) is described that intercepts a late-stage intermediate of a previous total synthesis; from there on, this challenging target can be reached in a small number of steps. Key to success was a sequence of a molybdenum-catalyzed ring-closing alkyne metathesis (RCAM) reaction to forge the macrocyclic frame, followed by a gold-catalyzed and strictly regioselective transannular hydroalkoxylation of the resulting cycloalkyne that allows the intricate oxygenation pattern of the macrolactone ring of 1 to be properly set. The required cyclization precursor 5 was assembled by the arguably most advanced fragment coupling process based on an Evans-Tishchenko redox esterification known to date, which was optimized to the extent that the precious coupling partners could be used in an almost equimolar ratio (6/7 1:1.3). The preparation of these building blocks features, inter alia, the power of the Sc(OTf)(3)-catalyzed Leighton crotylation as well as the superb selectivities of alkene cross metathesis, asymmetric keto-ester hydrogenation, and the Jacobsen epoxidation/epoxide resolution technologies. |
| Databáze: | OpenAIRE |
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