Total synthesis, relay synthesis, and structural confirmation of the C18-norditerpenoid alkaloid neofinaconitine Journal Article
| Authors: | Shi, Y.; Wilmot, J. T.; Nordstrøm, L. U.; Tan, D. S.; Gin, D. Y. |
| Article Title: | Total synthesis, relay synthesis, and structural confirmation of the C18-norditerpenoid alkaloid neofinaconitine |
| Abstract: | 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. © 2013 American Chemical Society. |
| Journal Title: | Journal of the American Chemical Society |
| Volume: | 135 |
| Issue: | 38 |
| ISSN: | 0002-7863 |
| Publisher: | American Chemical Society |
| Date Published: | 2013-09-01 |
| Start Page: | 14313 |
| End Page: | 14320 |
| Language: | English |
| DOI: | 10.1021/ja4064958 |
| PROVIDER: | scopus |
| PMCID: | PMC3883312 |
| PUBMED: | 24040959 |
| DOI/URL: | |
| Notes: | "Export Date: 1 November 2013" - "CODEN: JACSA" - "Source: Scopus" |
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