Straightforward access to novel cytotoxic phytosphingosine-like aminotriols from l-erythrose chiron

Abstract

A divergent approach to a small library of long-chain 6-amino-1,4,5-triols as novel phytosphingosine-type entities, together with their preliminary cytotoxic evaluation, was achieved. Construction of the target compounds addressed two key aspects. First, the installation of a carbon-nitrogen bond via two prototypes of [3,3]-sigmatropic rearrangements and second the introduction of an alkyl side chain unit by using a late stage olefin cross-metathesis process. As shown in cell viability experiments, the corresponding HCl salts proved to be the most cytotoxic derivatives among all the tested substances, with IC50 values in the lower micromolar range on the Jurkat, HeLa and HCT-116 cell lines.