7633-68-3Relevant articles and documents
Total synthesis, relay synthesis, and structural confirmation of the C18-norditerpenoid alkaloid neofinaconitine
Shi, Yuan,Wilmot, Jeremy T.,Nordstrom, Lars Ulrik,Tan, Derek S.,Gin, David Y.
supporting information, p. 14313 - 14320 (2013/10/21)
The first total synthesis of the C18-norditerpenoid aconitine alkaloid neofinaconitine and relay syntheses of neofinaconitine and 9-deoxylappaconitine from condelphine are reported. A modular, convergent synthetic approach involves initial Diels-Alder cycloaddition between two unstable components, cyclopropene 10 and cyclopentadiene 11. A second Diels-Alder reaction features the first use of an azepinone dienophile (8), with high diastereofacial selectivity achieved via rational design of siloxydiene component 36 with a sterically demanding bromine substituent. Subsequent Mannich-type N-acyliminium and radical cyclizations provide complete hexacyclic skeleton 33 of the aconitine alkaloids. Key endgame transformations include the installation of the C8-hydroxyl group via conjugate addition of water to a putative strained bridghead enone intermediate 45 and one-carbon oxidative truncation of the C4 side chain to afford racemic neofinaconitine. Complete structural confirmation was provided by a concise relay synthesis of (+)-neofinaconitine and (+)-9-deoxylappaconitine from condelphine, with X-ray crystallographic analysis of the former clarifying the NMR spectral discrepancy between neofinaconitine and delphicrispuline, which were previously assigned identical structures.
