Enantioselective Total Synthesis of (+)‐Garsubellin A

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 Alzheimers 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 twelvestep, protecting group-free synthetic route has enabled the syntheses of both the natural (À)-garsubellin A and its unnatural (+)-antipode for biological evaluations.Scheme 1. Structure and retrosynthesis of Garsubellin A.

The Total Synthesis of Hyperfirin via a Cyclooctadiene Strategy

“…Along with their structural variety, PPAPs exhibit a multitude of intriguing biological activities . As a result, numerous synthetic efforts have been undertaken in the past few decades dedicated to the total synthesis of PPAPs (Figure , 2 , − 3 , − 4 , − 5 , − 6 ). Surprisingly, the bicyclic core structure is mostly derived from six-membered ring structures.…”