Biomimetic Synthesis of trans,syn,trans-Fused Polyoxepanes: Remarkable Substituent Effects on the endo-Regioselective Oxacyclization of Polyepoxides

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• 作者：Jason C. Valentine ; Frank E. McDonald ; Wade A. Neiwert ; and Kenneth I. Hardcastle
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：April 6, 2005
• 年：2005
• 卷：127
• 期：13
• 页码：4586 - 4587
• 全文大小：81K
• 年卷期：v.127,no.13(April 6, 2005)
• ISSN：1520-5126

文摘

The biogenesis of trans,syn,trans-fused polycyclic ether substructures of neurotoxic natural products of the brevetoxin-ciguatoxin family may involve regio- and stereoselective oxacyclizations of polyepoxides. We report that a biomimetic Lewis acid-promoted cyclization of 1 to 2 proceeds with endo-regioselectivity and anti-stereospecificity at each position of nucleophilic addition (C3, C7, C11, and C15 in 1) when the tandem cyclization cascade is terminated by a carbonyl oxygen nucleophile. In contrast to expectations from earlier reports with simpler epoxide substrates, alkyl substituents are not required at internal epoxide positions corresponding to C7 and C11 in polyepoxide 1. Furthermore, we report that trimethylsilyl serves as a removable regioselectivity-directing substituent at positions corresponding to C3 of 1. These results greatly expand the potential applications of this biomimetic oxacyclization cascade to the synthesis of fused polycyclic ether natural products.