Sphingolipids Cyclic Derivatives: Occurrence, Biological Relevance and Synthetic Approaches

Stephanie      Ballereau; Michel      Baltas; Yves      Genisson

doi:10.2174/138527211794785127

Abstract

Sphingolipids (SLs) are ubiquitous membrane constituents that have emerged as essential lipid mediators involved in signal transduction and cancer development. Due to the implication of SLs in the alteration of cell proliferation, adhesion or migration, their metabolism has been targeted in search for novel anti-cancer therapeutic approaches. In this context, much attention has been directed towards SLs analogues interfering with these complex signalization pathways as well as the immune system.

A general structural modulation of the basic sphingosine backbone of SLs concerns its cyclisation into various types of conformationally constrained derivatives. Different series of both natural and synthetic compounds can be considered according to this common structural feature. The present review article lists these naturally occuring sphingolipids cyclic derivatives including anhydrophytosphingosine-type marine products pachastrissamine (jaspine B), penaresidine/penazetidine, broussonetine, prosopine/prosopinine/prosophylline derivatives, as well as conceptually related synthetic products. A brief statement of their biological activity is presented. Detailed informations concerning the organic synthetic aspects are given with emphasize on the natural azetidine, pyrrolidine and all the synthetic analogues that had never been reviewed before.

Keywords: Ceramide, broussonetine, jaspine, penaresidine, prosophylline, sphingosine, sphingolipids (SLs), palmitoyl CoA, sphingomyelin, stereochemistry, pyrrolidine, piperidine, prosafrinine, melanoma cells, β-glucosidase, β-galactosidase, β-mannosidase