1. Enantioselective Total Synthesis of (+)‐Garsubellin A
- Author
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Jinglong Chen, Chulbom Lee, Minchul Choi, and Dongseok Jang
- Subjects
natural products ,Stereochemistry ,carbocycles ,Molecular Conformation ,Cyclohexanone ,carbonylation ,Crystallography, X-Ray ,Catalysis ,PPAP ,Bridged Bicyclo Compounds ,chemistry.chemical_compound ,Aldol reaction ,Natural Products | Hot Paper ,total synthesis ,Meroterpene ,Biological Products ,Bicyclic molecule ,Terpenes ,Chemistry ,Communication ,Enantioselective synthesis ,Total synthesis ,Stereoisomerism ,General Chemistry ,General Medicine ,Communications ,Cyclization ,Stereoselectivity ,Conjugate - Abstract
Garsubellin A is a meroterpene capable of enhancing the enzyme choline acetyltransferase whose decreased level is believed to play a central role in the symptoms of Alzheimer's disease. Due to the potentially useful biological activity together with the novel bridged and fused cyclic molecular architecture, garsubellin A has garnered substantial synthetic interest, but its absolute stereostructure has been undetermined. We report here the first enantioselective total synthesis of (+)‐garsubellin A. Our synthesis relies on stereoselective fashioning of a cyclohexanone framework and double conjugate addition of 1,2‐ethanedithiol that promotes aldol cyclization to build the bicyclic [3.3.1] skeleton. The twelve‐step, protecting group‐free synthetic route has enabled the syntheses of both the natural (−)‐garsubellin A and its unnatural (+)‐antipode for biological evaluations., The first enantioselective total synthesis of garsubellin A establishes the absolute stereostructure of the plant‐derived meroterpene that enhances the choline acetyltransferase enzyme responsible for the biosynthesis of the neurotransmitter acetylcholine. The 12‐step, protecting group‐free synthesis features use of a dithiolane for efficient construction of the bridged and fused ring system.
- Published
- 2021