pachastrissamine and phytosphingosine

A straightforward access to pyrrolidine-based analogues of jaspine B was developed. Five stereoisomers were prepared including the all-cis derivatives presenting the configuration of the natural anhydrophytosphingosine. The synthesis of the latter relied on an original Staudinger-type cyclization process. The compounds were evaluated regarding their ability to alter tumor cells' viability and to interfere with the metabolism of sphingolipids.

Topics: Animals; Cell Line, Tumor; Humans; Melanoma, Experimental; Mice; Pyrrolidines; Sphingosine; Stereoisomerism

The synthesis of isomeric jaspines (anhydro phytosphingosines), arising from intramolecular cyclization of the corresponding phytosphingosines with different configurations at C3 and C4 positions of the sphingoid backbone, is reported. Natural jaspine B is the most cytotoxic isomer on A549 cells and it induces cell death in a dose-dependent manner. The cytotoxicity of jaspine B has been correlated with a significant increase of intracellular dihydroceramides, which seem to play an active role in autophagy.

Topics: Autophagy; Cell Death; Cell Line; Ceramides; Cyclization; Dose-Response Relationship, Drug; Humans; Sphingosine; Stereoisomerism

[reaction: see text] The syntheses of the cytotoxic natural product pachastrissamine and its unnatural 4-epi-congener were accomplished starting from a natural phytosphingosine. The relatively unstrained cyclic sulfate intermediate smoothly underwent the 5-endo cyclization to yield the 2,3,4-trisubstituted tetrahydrofuran ring system of pachastrissamine. The corresponding epoxy alcohol afforded the 4-epi-congener via a tosylate-mediated double inversion process.

Topics: Cyclization; Epoxy Compounds; Models, Chemical; Sphingosine; Sulfates

[reaction: see text] The natural product pachastrissamine, an anhydrophytosphingosine derivative isolated from various sponges and endowed with cytotoxic activity against several human carcinoma cell lines, was synthesized in three steps and with 72% overall yield from d-ribo-phytosphingosine.

Topics: Furans; Indicators and Reagents; Models, Molecular; Molecular Conformation; Ribose; Sphingosine