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

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