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Issue 14, 2010
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Flexible and enantioselective access to jaspine B and biologically active chain-modified analogues thereof

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Abstract

Whereas the all-cis tetrahydrofuran framework of the cytotoxic anhydrophytosphingosine jaspine B is considered as a relevant pharmacophore, little is known about the influence of the aliphatic chain of this amphiphilic molecule on its activity. We developed a synthetic strategy allowing flexible introduction of various lipophilic fragments in the jaspine's skeleton. The route was validated with two distinct approaches to jaspine B. Five chain-modified analogues were also prepared. Biological evaluation of these derivatives demonstrated a good correlation between their cytotoxicity and their capacity to inhibit conversion of ceramide into sphingomyelin in melanoma cells. A series of potent and selective inhibitors of sphingomyelin production was thus identified. Furthermore, the good overall potency of an ω-aminated analogue allowed us to dissociate of the pharmacological action of jaspine B from its amphiphilic nature.

Graphical abstract: Flexible and enantioselective access to jaspine B and biologically active chain-modified analogues thereof

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Publication details

The article was received on 16 Mar 2010, accepted on 28 Apr 2010 and first published on 24 May 2010


Article type: Paper
DOI: 10.1039/C004218H
Citation: Org. Biomol. Chem., 2010,8, 3227-3243
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    Flexible and enantioselective access to jaspine B and biologically active chain-modified analogues thereof

    Y. Salma, S. Ballereau, C. Maaliki, S. Ladeira, N. Andrieu-Abadie and Y. Génisson, Org. Biomol. Chem., 2010, 8, 3227
    DOI: 10.1039/C004218H

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