Total synthesis and comparative analysis of orlistat, valilactone, and a transposed orlistat derivative: Inhibitors of fatty acid synthase
| Autor: | Daniel Romo, Jeffrey W. Smith, Gil Ma, Robyn D. Richardson, Yatsandra Oyola, Manuel Zancanella |
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| Rok vydání: | 2006 |
| Předmět: |
Stereochemistry
Stereoisomerism Biochemistry law.invention Lactones Thioesterase law Valilactone Cell Line Tumor medicine Humans Physical and Theoretical Chemistry Enzyme Inhibitors Orlistat biology Olefin metathesis Chemistry Organic Chemistry Total synthesis Fatty acid synthase Recombinant DNA biology.protein Anti-Obesity Agents Fatty Acid Synthases medicine.drug |
| Zdroj: | Organic letters. 8(20) |
| ISSN: | 1523-7060 |
| Popis: | Concise syntheses of orlistat (Xenical), a two-carbon transposed orlistat derivative, and valilactone are described that employ the tandem Mukaiyama aldol-lactonization (TMAL) process as a key step. This process allows facile modification of the alpha-side chain. Versatile strategies for modifying the delta-side chain are described, involving cuprate addition and olefin metathesis. Comparative antagonistic activity of these derivatives toward a recombinant form of the thioesterase domain of fatty acid synthase is reported along with comparative activity-based profiling. |
| Databáze: | OpenAIRE |
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