Stereoselective Construction of C 2-Symmetric Adjacent Bis-α,α′-cis-Disubstituted THF Skeleton via Double Intramolecular Amide Enolate Alkylation: Total Syntheses of (+)-Membranacin and (+)-Squamocin-N

초록

Described herein is the highly stereoselective and concise first asymmetric total synthesis of (+)-squamocin-N (1b) bearing a C15-C24 adjacent bis-tetrahydrofuran (THF) backbone with threo/cis/threo/cis/threo stereochemistry. This approach features construction of C 2-symmetric adjacent cis/threo/cis bis-THF core 5 via a novel double intramolecular amide enolate alkylation (IAEA) protocol, reductive desymmetrization of C 2-symmetric bis-THF 5, and chelation-controlled nucleophilic addition (CCNA) as the key steps. In addition, (+)-membranacin (1a), the C24 epimer of 1b, was synthesized via Mitsunobu inversion.

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