A biosynthetically inspired synthesis of (−)-berkelic acid and analogs

Christopher F. Bender, Christopher L. Paradise, Vincent M. Lynch, Francis K. Yoshimoto, Jef K. De Brabander

Research output: Contribution to journalArticle

  • 4 Citations

Abstract

We describe a complete account of our total synthesis and biological evaluation of (−)-berkelic acid and analogs. We delineate a synthetic strategy inspired by a potentially biomimetic union between the natural products spicifernin and pulvilloric acid. After defining optimal parameters, we executed a one-pot silver-mediated in situ dehydration of an isochroman lactol to methyl pulvillorate, the cycloisomerization of a spicifernin-like alkynol to the corresponding exocyclic enol ether, and a subsequent cycloaddition to deliver the tetracyclic core of berkelic acid. Our studies confirm that the original assigned berkelic acid structure is not stable and equilibrates into a mixture of 4 diastereomers, fully characterized by X-ray crystallography. In addition to berkelic acid, C22-epi-berkelic acid, and nor-berkelic acids, we synthesized C26-oxoberkelic acid analogs that were evaluated against human cancer cell lines. In contrast to data reported for natural berkelic acid, our synthetic material and analogs were found to be devoid of activity.

LanguageEnglish (US)
Pages909-919
Number of pages11
JournalTetrahedron
Volume74
Issue number9
DOIs
StatePublished - Mar 1 2018

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Biomimetics
Acids
Cycloaddition
X ray crystallography
X Ray Crystallography
Cycloaddition Reaction
berkelic acid
Biological Products
Dehydration
Silver
Ether
Cells
Cell Line
Neoplasms

Keywords

  • Cycloaddition
  • Cycloisomerization
  • Natural products
  • Quinone methide
  • Spiroketals

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

A biosynthetically inspired synthesis of (−)-berkelic acid and analogs. / Bender, Christopher F.; Paradise, Christopher L.; Lynch, Vincent M.; Yoshimoto, Francis K.; De Brabander, Jef K.

In: Tetrahedron, Vol. 74, No. 9, 01.03.2018, p. 909-919.

Research output: Contribution to journalArticle

Bender, Christopher F. ; Paradise, Christopher L. ; Lynch, Vincent M. ; Yoshimoto, Francis K. ; De Brabander, Jef K. / A biosynthetically inspired synthesis of (−)-berkelic acid and analogs. In: Tetrahedron. 2018 ; Vol. 74, No. 9. pp. 909-919.
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