Synthesis of Cardiotonic Steroids Oleandrigenin and Rhodexin B.

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  • Author(s): Fejedelem Z;Fejedelem Z; Carney N; Carney N; Nagorny P; Nagorny P
  • Source:
    The Journal of organic chemistry [J Org Chem] 2021 Aug 06; Vol. 86 (15), pp. 10249-10262. Date of Electronic Publication: 2021 Jul 13.
  • Publication Type:
    Journal Article; Research Support, N.I.H., Extramural
  • Language:
    English
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 2985193R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-6904 (Electronic) Linking ISSN: 00223263 NLM ISO Abbreviation: J Org Chem Subsets: MEDLINE
    • Publication Information:
      Publication: Columbus Oh : American Chemical Society
      Original Publication: Easton, Pa. [etc.]
    • Subject Terms:
      Antineoplastic Agents* ; Cardiac Glycosides*; Cardenolides ; Oxidation-Reduction
    • Abstract:
      This article describes a concise synthesis of cardiotonic steroids oleandrigenin ( 7 ) and its subsequent elaboration into the natural product rhodexin B ( 2 ) from the readily available intermediate ( 8 ) that could be derived from the commercially available steroids testosterone or DHEA via three-step sequences. These studies feature an expedient installation of the β16-oxidation based on β14-hydroxyl-directed epoxidation and subsequent epoxide rearrangement. The following singlet oxygen oxidation of the C17 furan moiety provides access to oleandrigenin ( 7 ) in 12 steps (LLS) and a 3.1% overall yield from 8 . The synthetic oleandrigenin ( 7 ) was successfully glycosylated with l-rhamnopyranoside-based donor 28 using a Pd(II)-catalyst, and the subsequent deprotection under acidic conditions provided cytotoxic natural product rhodexin B ( 2 ) in a 66% yield (two steps).
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    • Grant Information:
      R35 GM136341 United States GM NIGMS NIH HHS
    • Accession Number:
      0 (Antineoplastic Agents)
      0 (Cardenolides)
      0 (Cardiac Glycosides)
      465-15-6 (oleandrigenin)
    • Publication Date:
      Date Created: 20210713 Date Completed: 20211005 Latest Revision: 20231108
    • Publication Date:
      20231215
    • Accession Number:
      PMC8582021
    • Accession Number:
      10.1021/acs.joc.1c00985
    • Accession Number:
      34255963