title: Flexible, polymer-supported synthesis of sphingosine derivatives provides ceramides with enhanced biological activity.
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.
authors.affiliation: Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rössle-Str. 10, 13125 Berlin, Germany.
authors.forename: Adeeb
authors.initials: A
authors.lastname: El-Dahshan
authors.affiliation: Chemical-Pharmaceutical Engineering, School of Applied Medical Sciences, German-Jordanian University, P.O. Box 35247, Amman 11180, Jordan.
authors.forename: Samer I
authors.initials: SI
authors.lastname: Al-Gharabli
authors.affiliation: Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rössle-Str. 10, 13125 Berlin, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Radetzki
authors.affiliation: College of Pharmacy, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates.
authors.forename: Taleb H
authors.initials: TH
authors.lastname: Al-Tel
authors.affiliation: Organic Chemistry Division, National Chemical Laboratory, Homi Bhabha Road, Pune 411 008, India.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Kumar
authors.affiliation: Institute of Pharmacy, Free University Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany; Leibniz Institute for Molecular Pharmacology (FMP), Robert-Rössle-Str. 10, 13125 Berlin, Germany. Electronic address: joerg.rademann@fu-berlin.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Rademann
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002518:Ceramides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D056945:Hep G2 Cells; D006801:Humans; D015394:Molecular Structure; D011108:Polymers / Q000737:chemistry*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002518:Ceramides; D011108:Polymers; D013110:Sphingosine
keywords: Apoptosis; Ceramide; Lipid rafts; Lipids; Sphingosine