| Abstract
| - The preparation of an established intermediate in a total synthesis of hemibrevetoxin B is described.The acid-catalyzed cyclization of trans-4,5-epoxyoctane-2,7-dione exhibited a valuable mixture ofkinetic and thermodynamic control: stereospecific epoxide opening was followed by equilibrationof the products to provide the required trans-fused octahydropyrano[3,2-b]pyran ring system. Two-directional elaboration, by acetal substitution, ozonolysis, and sulfur ylide-mediated epoxidation,provided a centrosymmetric diepoxide. The key step of the synthesis was the first desymmetrizationof a centrosymmetric molecule in natural product synthesis: Jacobsen asymmetric epoxidehydrolysis and acetonization provided the known synthetic intermediate in 97% yield and >95%ee over two steps. The exploitation of the center of symmetry of the AB ring system of the naturalproduct contributed greatly to the efficiency (eight steps, 34% overall yield) of the synthesis.
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