Total synthesis, biological evaluation and biosynthetic re-evaluation of Illicium-derived neolignans

Arnold, Robert E.; Saska, Jan; Mesquita-Ribeiro, Raquel; Dajas-Bailador, Federico; Taylor, Laurence; Lewis, William; Argent, Stephen; Shao, Huiling; Houk, Kendall N.; Denton, Ross M.

Abstract

We report the first total syntheses of simonsol F (3), simonsinol (5), fargenin (4), and macranthol (6) in addition to syntheses of simonsol C (2), simonsol G (1), and honokiol (14). The syntheses are based upon a phosphonium ylide-mediated cascade reaction and upon natural product isomerization reactions which proceed through Cope rearrangements of putative biosynthetic dienone intermediates. As a corollary of the natural product isomerization reactions, we propose an alternative biosynthesis of honokiol (14), simonsinol (5), and macranthol (6) which unites the natural products in this family under a single common precursor, chavicol (7). Finally, we demonstrate that simonsol C (2) and simonsol F (3) promote axonal growth in primary mouse cortical neurons.

Citation

Arnold, R. E., Saska, J., Mesquita-Ribeiro, R., Dajas-Bailador, F., Taylor, L., Lewis, W., Argent, S., Shao, H., Houk, K. N., & Denton, R. M. (2024). Total synthesis, biological evaluation and biosynthetic re-evaluation of Illicium-derived neolignans. Chemical Science, 15(30), 11783-11793. https://doi.org/10.1039/d4sc03232b

• Journal Article Type: Article
• Acceptance Date: Jun 13, 2024
• Online Publication Date: Jun 19, 2024
• Publication Date: Aug 14, 2024
• Deposit Date: Jul 8, 2024
• Publicly Available Date: Jul 9, 2024
• Journal: Chemical Science
• Print ISSN: 2041-6520
• Electronic ISSN: 2041-6539
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Issue: 30
• Pages: 11783-11793
• DOI: https://doi.org/10.1039/d4sc03232b
• Public URL: https://nottingham-repository.worktribe.com/output/36877023