Total Synthesis of ent-Pregnanolone Sulfate and Its Biological Investigation at the NMDA Receptor
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Cyclization MeSH
- Molecular Structure MeSH
- Pregnanolone chemical synthesis MeSH
- Receptors, N-Methyl-D-Aspartate MeSH
- Sulfates MeSH
- Stereoisomerism MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Pregnanolone MeSH
- Receptors, N-Methyl-D-Aspartate MeSH
- Sulfates MeSH
A unique asymmetric total synthesis of the unnatural enantiomer of pregnanolone, as well as a study of its biological activity at the NMDA receptor, is reported. The asymmetry is introduced by a highly atom-economic organocatalytic Robinson annulation. A new method for the construction of the cyclopentane D-ring consisting of CuI-catalyzed conjugate addition and oxygenation followed by thermal cyclization employing the persistent radical effect was developed. ent-Pregnanolone sulfate is surprisingly only 2.6-fold less active than the natural neurosteroid.
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