Stereoselective total synthesis of (3Z)- and (3E)-elatenynes.

We describe here the highly stereoselective total synthesis of the Laurencia C15 acetogenins (3Z)- and (3E)-elatenynes having a 7,12-dibromo-6,9-cis-10,13-cis adjacent bis-tetrahydrofuran (THF) core. The present synthesis features a highly stereoselective, protecting group-dependent, chelate-controlled intramolecular amide enolate alkylation (IAEA) for the synthesis of key intermediate 7-hydroxy-6,7-cis-6,9-cis-THF intermediate 10, deployment of the sequential ate complex (n-BuLi/DIBAL-H) reduction/Keck allylation/cross metathesis (CM) protocol for the stereoselective introduction of the C(10)-C(15) unit, a sequential Sharpless asymmetric dihydroxylation (SAD)/intramolecular Williamson etherification for the construction of the 10,13-cis-THF ring, and a modified Nakata chloromethanesulfonate-mediated SN2 displacement for the 7,12-dibromo functionality. Furthermore, our strategy based on chelate-controlled IAEA methodology would provide access to any member of the C15 adjacent bis-THF acetogenin class.

Total Synthesis and Structure Confirmation of (-)-Asimitrin, a C37 Annonaceous Acetogenin with a Hydroxylated Adjacent Bis-Tetrahydrofuran Core.

The total synthesis and structure confirmation of the potent cytotoxic agent (-)-asimitrin (1), a C37 annonaceous acetogenin having a hydroxylated adjacent bis-tetrahydrofuran (THF) core, are described. The present synthesis features a highly stereoselective, chelate-controlled intramolecular amide enolate alkylation (IAEA) for the synthesis of key intermediate 17-hydroxy-16,17-erythro-16,19-trans-THF 6, our direct ketone synthesis/l-Selectride reduction protocol for stereoselective introduction of the C(21)-C(34) unit, Sharpless asymmetric dihydroxylation (SAD), and internal Williamson etherification for construction of the 20,23-trans-THF ring.

Highly Stereodivergent Construction of a C2-Symmetric cis,cis- and trans,trans-2,6-Dioxabicyclo[3.3.0]octane Framework by Double Intramolecular Amide Enolate Alkylation: Total Synthesis of (+)-Laurenidificin and (+)-Aplysiallene.

The highly stereoselective construction of C2-symmetric cis,cis- and trans,trans-2,6-dioxabicyclo[3.3.0]octane (fused bis-tetrahydrofuran) skeletons 4a and 4b has been accomplished via a novel stereodivergent double intramolecular amide enolate alkylation of common cyclization substrate 5 through the judicious choice of "chelate" versus crown ether-promoted "nonchelate" control. Application of this methodology has provided access to substrate-controlled concise total syntheses of (+)-laurenidificin (3) and (+)-aplysiallene (ent-2), which possess cis/cis- and trans/trans-fused bis-tetrahydrofuran cores, respectively.