Stereoselective synthesis and antiproliferative activity of the isomeric sphinganine analogues.

Affiliation

Institute of Chemical Sciences, Department of Organic Chemistry, P.J. Šafárik University, Moyzesova 11, 040 01, Košice, Slovak Republic. Electronic address: [Email]

Abstract

A flexible synthetic approach to biologically active sphingoid base-like compounds with a 3-amino-1,2-diol framework was achieved through a [3,3]-sigmatropic rearrangement and late stage olefin cross-metathesis as the key transformations. The stereochemistry of the newly created stereogenic centre was assigned via a single crystal X-ray analysis of the (4S,5R)-5-(hydroxymethyl)-4-vinyloxazolidine-2-thione. In order to rationalise the observed stereoselectivity of the aza-Claisen rearrangement, DFT calculations were carried out. The targeted isomeric sphingoid bases were screened in vitro for anticancer activity on a panel of seven human malignant cell lines. Cell viability experiments revealed that C17-homologues are more active than their C12 congeners.

Keywords

Antiproliferative activity,Aza-claisen rearrangement,Isosphinganines,Olefin cross-metathesis,Sphingoid bases,Sphingolipids,