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Concise total syntheses of several 5/7/6 norcembranoids, including ineleganolide, scabrolide B, sinuscalide C, and fragilolide A have been achieved through a fragment coupling/ring closure approach. The central seven-membered ring was forged through sequential Mukaiyama–Michael/aldol reactions using norcarvone and a decorated bicyclic lactone incorporating a latent electrophile. Subsequent manipulations installed the reactive enedione motif and delivered scabrolide B in 11 steps from a chiral pool-derived enone. Finally, ineleganolide, sinuscalide C, and fragilolide A were each accessed in one additional step.
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The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′‐ epi ‐Leucophyllidine
Abstract A synthetic approach to the heterodimeric bisindole alkaloid leucophyllidine is disclosed herein. An enantioenriched lactam building block, synthesized through palladium‐catalyzed asymmetric allylic alkylation, served as the precursor to both hemispheres. The eburnamonine‐derived fragment was synthesized through a Bischler–Napieralski/hydrogenation approach, while the eucophylline‐derived fragment was synthesized by Friedländer quinoline synthesis and two sequential C−H functionalization steps. A convergent Stille coupling and phenol‐directed hydrogenation united the two monomeric fragments to afford 16′‐epi‐leucophyllidine in 21 steps from commercial material.
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- Award ID(s):
- 1700982
- PAR ID:
- 10271956
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 60
- Issue:
- 33
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 17957-17962
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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