Total synthesis of diptoindonesin G and its analogues as selective modulators of estrogen receptors

  • Org Biomol Chem. 2016 Sep 26;14(38):8927-8930. doi: 10.1039/c6ob01657j.
Ji-Tian Liu  1 ,  Truman J Do  2 ,  Christopher J Simmons  3 ,  John C Lynch  4 ,  Wen Gu  5 ,  Zhi-Xiong Ma  6 ,  Wei Xu  2 ,  Weiping Tang  7
Affiliations
  • 1. School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA and School of Pharmaceutical Science and Technology, Tianjin University, Tianjin, 300072, P. R. China.
  • 2. McArdle Laboratory for Cancer Research, Wisconsin Institute for Medical Research, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • 3. School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA and Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA.
  • 4. School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA.
  • 5. School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA and Jiangsu Key Lab of Biomass-based Green Fuels and Chemicals, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, PR China.
  • 6. Medicinal Chemistry Center, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53706, USA. [email protected].
  • 7. School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53705, USA and Department of Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA and Medicinal Chemistry Center, School of Pharmacy, University of Wisconsin-Madison, Madison, WI 53706, USA. [email protected].
PMID: 27714255 DOI: 10.1039/c6ob01657j
Abstract

We have developed a versatile synthetic strategy for the synthesis of the natural product diptoindonesin G and its analogues as selective modulators of estrogen receptors. The strategy involves a regioselective dehydrative cyclization of arylacetals, a regioselective bromination of benzofurans, a sequential cross-coupling of bromo-benzofurans with aryl boronic acids, and a BBr3-mediated tandem cyclization and demethylation. Preliminary biological studies uncovered the critical and dispensable phenolic hydroxyl groups in the natural product and also revealed unexpected selectivity for isoforms of Estrogen receptor.

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