Recent Advances in the Synthesis of Sphingosine and Phytosphingosine, Molecules of Biological Significance

Jose      Antonio Morales-Serna; Josep      Llaveria; Yolanda      Diaz; M.      Isabel Matheu; Sergio      Castillon

Abstract

Due to the relevant biological role of sphingosines, ceramides and glycosyl ceramides, and the increasing demand of these compounds for biological evaluations, developing methods targeting sphingosine and phytosphingosine and derivatives have attracted the interest of researchers. The review initially presents the structural features of these compounds, presenting the different types of nomenclature of phytosphingosines, and the more relevant biological properties, as well as the biochemical synthesis. The synthetic procedures using products of the chiral pool, mainly carbohydrates and serine derivatives, are progressively shifted by asymmetric synthesis procedures, and particularly to those based on catalytic reactions. In this way, the review presents separately the synthetic procedures leading to sphingosine and phytosphingosine, and each case the synthesis based on the chiral pool are presented separately from the asymmetric synthesis. In this last case the methods are classified depending of the strategy used for inducing chirality, chiral auxiliary, chiral reagent or catalytic procedures, to which special attention is devoted. The syntheses are discussed in detail and reagents and yields for each step are provided. The review also rationalizes and integrates the different synthetic procedures from the point of view of construction the chiral fragment of these molecules.

Keywords: Sphingosine, phytosphingosine, sphingolipids, signalling compounds, cell membrane components, ceramides, Glycosphingolipids, glycosaminoglycans, hydrophobic ceramide, Agelas mauritianus, interferon-γ, interleukin-4, interleukin-2, dihydroceramide desaturase, sphingomyelin, galactosylceramide, glucosylceramide, sphinganines, n-dodecylmagnesium bromide, 3-O-benzoylazidosphingosine, 1-thio-β-D-xylopyranoside, α-phenylsulfonyl glycal derivative, Candida antarctiva, tri-tert-butoxyaluminohydride, D-erythro-sphingosine, 6-Hydroxy-4E-sphingosine, 1-phenyl-1H-tetrazole-5-yl thioether, D-erythroazidosphingosine, Dribo-phytospingosine, flash chromatography, (S)-Nbenzyl-N-(α-methylbenzyl)amide, D-glucosamine hydrochloride, D-ribo-phytosphingosine, 6-halogenated 2-acetamido-2-deoxy-allopyranoside, D-xylo-phytosphingosine, Z-2-alkenylaziridine, osmium tetroxide, N-methylmorpholine oxide, L-ribo-phytosphingosine, 1-hexadecene