Total synthesis, relay synthesis, and structural confirmation of the C18-norditerpenoid alkaloid neofinaconitine

Yuan Shi, Jeremy T. Wilmot, Larsulrik R. Nordstroem, Derek S. Tan, David Y. Gin

Research output: Contribution to journalArticle

47 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)14313-14320
Number of pages8
JournalJournal of the American Chemical Society
Volume135
Issue number38
DOIs
StatePublished - Sep 25 2013

Fingerprint

Alkaloids
Diterpenes
Aconitine
Cycloaddition Reaction
Cycloaddition
Bromine
Cyclization
Cyclopentanes
Nuclear magnetic resonance
X rays
Carbon
Skeleton
Hydroxyl Radical
X-Rays
neofinaconitine
Water

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Total synthesis, relay synthesis, and structural confirmation of the C18-norditerpenoid alkaloid neofinaconitine. / Shi, Yuan; Wilmot, Jeremy T.; Nordstroem, Larsulrik R.; Tan, Derek S.; Gin, David Y.

In: Journal of the American Chemical Society, Vol. 135, No. 38, 25.09.2013, p. 14313-14320.

Research output: Contribution to journalArticle

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