A chiral pool approach for asymmetric syntheses of both antipodes of equol and sativan

Chinni Yalamanchili, Amar G. Chittiboyina, Sateesh Chandra Kumar Rotte, John A. Katzenellenbogen, William G. Helferich, Ikhlas A. Khan

Research output: Contribution to journalArticlepeer-review

Abstract

For the first time, both antipodes of the isoflavans, equol and sativan were synthesized in >98% ee with good overall yields starting from readily available starting materials. The chiral isoflavan, (−)-equol is produced from soy isoflavones, formonentin and daidzein by the action of intestinal bacteria in certain groups of population and other chiral isoflavans are reported from various phytochemical sources. To produce these chiral isoflavans in gram quantities, Evans’ enantioselective aldol condensation was used as a chiral-inducing step to introduce the required chirality at the C-3 position. Addition of chiral boron-enolate to substituted benzaldehyde resulted in functionalized syn-aldol products with >90% yield and excellent diastereoselectivity. Functional group transformations followed by intramolecular Mitsunobu reaction and deprotection steps resulted the target compounds, S-(−)-equol and S-(+)-sativan, with high degree of enantiopurity. By simply switching the chiral auxiliary to (S)-4-benzyloxazolidin-2-one and following the same synthetic sequence the antipodes, R-(+)-equol and R-(−)-sativan were achieved. Both enantiomers are of interest from a clinical and pharmacological perspective and are currently being developed as nutraceutical and pharmacological agents. This flexible synthetic process lends itself quite readily to the enantioselective syntheses of other biologically active C-3 chiral isoflavans.

Original languageEnglish (US)
Pages (from-to)2020-2029
Number of pages10
JournalTetrahedron
Volume74
Issue number16
DOIs
StatePublished - Apr 19 2018

Keywords

  • Asymmetric synthesis
  • Chirality
  • Evans aldol
  • Isoflavans

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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