2. Academic Validation
  3. Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

Heck- and Suzuki-coupling approaches to novel hydroquinone inhibitors of calcium ATPase

  • Beilstein J Org Chem. 2019 Apr 24:15:971-975. doi: 10.3762/bjoc.15.94.
Robert J Kempton 1,  Taylor A Kidd-Kautz 1,  Soizic Laurenceau 1,  Stefan Paula 2
Affiliations

Affiliations

  • 1 Department of Chemistry and Biochemistry, Northern Kentucky University, Nunn Drive, Highland Heights, KY 41099, USA.
  • 2 Department of Chemistry, Purdue University, Oval Drive, West Lafayette, IN 47907, USA.
PMID: 31164934 DOI: 10.3762/bjoc.15.94
Abstract

In this study, we explored Heck- and Suzuki-coupling methodology to modify the template 2,5-di-tert-butylhydroquinone (BHQ, 2), an inhibitor of the enzyme sarco/endoplasmic reticulum calcium ATPase (SERCA). We found that by utilizing Suzuki coupling, we could successfully attach a six-carbon tether to BHQ that terminated in a leucine moiety to obtain target 14. Similar to related compounds based on the structure of the natural product thapsigargin, 14 displayed inhibitory potency against SERCA activity. This makes 14 a suitable candidate for the future attachment of a deactivating peptide to convey specificity for prostate Cancer cells.

Keywords

Heck- and Suzuki-coupling reactions; calcium ATPase inhibitors; hydroquinones; prostate cancer; tethered amino acid.

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