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

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.

SUBMITTER: Arnold RE

PROVIDER: S-EPMC11290413 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Total synthesis, biological evaluation and biosynthetic re-evaluation of <i>Illicium</i>-derived neolignans.

Arnold Robert E RE Saska Jan J Mesquita-Ribeiro Raquel R Dajas-Bailador Federico F Taylor Laurence L Lewis William W Argent Stephen S Shao Huiling H Houk Kendall N KN Denton Ross M RM

Chemical science 20240619 30

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 o ...[more]

PMID: 39092111

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