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Flexible, polymer-supported synthesis of sphingosine derivatives provides ceramides with enhanced biological activity

Authors

  • A. El-Dahshan
  • S.I. Al-Gharabli
  • S. Radetzki
  • T.H. Al-Tel
  • P. Kumar
  • J. Rademann

Journal

  • Bioorganic and Medicinal Chemistry

Citation

  • Bioorg Med Chem 22 (19): 5506-5512

Abstract

  • A polymer-supported route for the synthesis of sphingosine derivatives is presented based on the C-acylation of polymeric phosphoranylidene acetates with an Fmoc-protected amino acid. The approach enables the flexible variation of the sphingosine tail through a deprotection-decarboxylation sequence followed by E-selective Wittig olefination cleavage. d-Erythro-sphingosine analogs have been synthesized by diastereoselective reduction of the keto group employing LiAlH(O-tBu)3 as reducing agent. The effect of ceramides and keto-ceramides on the proliferation of three cancer cell lines HEP G-2, PC-12 and HL-60 was investigated and a ceramide containing an aromatic sphingosine tail was identified as being most active.


DOI

doi:10.1016/j.bmc.2014.07.024