A Total Synthesis of Bifidenone

  • J Org Chem. 2017 Apr 21;82(8):4235-4241. doi: 10.1021/acs.joc.7b00202.
Zhongping Huang  1 ,  Russell B Williams  2 ,  Mark O'Neil-Johnson  2 ,  Gary R Eldridge  2 ,  John E Mangette  1 ,  Courtney M Starks  2
Affiliations
  • 1. Albany Molecular Research Inc., 1001 Main Street, Buffalo, New York 14203, United States.
  • 2. Sequoia Sciences, Inc., 1912 Innerbelt Business Center Drive, St. Louis, Missouri 63114, United States.
PMID: 28351141 DOI: 10.1021/acs.joc.7b00202
Abstract

The first total synthesis of bifidenone, a novel natural tubulin polymerization inhibitor, has been achieved in 12 steps starting from commercially available 1,4-dioxaspiro[4.5]decan-8-one. The synthesis includes a newly developed method to generate the dihydrobenzodioxolone core by palladium-catalyzed aerobic dehydrogenation. The three stereocenters were installed with an AD-mix-β dihydroxylation step followed by a late-stage palladium-catalyzed decarboxylation-allylation procedure. The absolute stereochemistry of 3 was determined via 13a by single-crystal X-ray analysis.

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