Synthesis and preliminary biological evaluation of β-carotene and retinoic acid oxidation products

E. M. Kithsiri Wijeratne, Manping X. Liu, Narendra B. Kantipudi, Claudia B. Brochini, A. A. Leslie Gunatilaka, Louise M. Canfield

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Synthesis of the β-carotene oxidation product, 2,3-dihydro-5,8-endoperoxy-β-apo-carotene-13-one (1) was achieved in six steps starting from β-ionone. Photo-oxygenation of all trans-retinoic acid (8) and 13-cis-retinoic acid (9) produced a mixture of 5S*,8S*-epidioxy-5,8-dihydroretinoic acid (10) and 13-cis-5S*,8S*-epidioxy-5,8-dihydroretinoic acid (11). Methylation of the crude photo-oxygenation mixture afforded the corresponding methyl esters 12 and 13, respectively, both of which underwent ready aerial oxidation yielding hitherto unknown oxidation products of retinoic acid identified as methyl 5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (14) and methyl 13-cis-5S*,8S*-epidioxy-9,10β-epoxy-5,8,9,10-tetrahydroretinoate (15). Evaluation of 1, all trans-retinoic acid (8), 13-cis-retinoic acid (9), and the photo-oxygenation products 10-15 in a panel of five cancer cell lines showed 1 to be inactive and that 11 is significantly cytotoxic compared with the other retinoic acid analogs suggesting the requirement of the carboxylic acid moiety and the cis-geometry of the 13(14) double bond for cytotoxic activity.

Original languageEnglish (US)
Pages (from-to)7875-7879
Number of pages5
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number23
DOIs
StatePublished - Dec 1 2006

Keywords

  • DACE
  • Oxidation products
  • Retinoic acid
  • Synthesis
  • β-Carotene

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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