Abstract

Background: Over the past decade, simple 1-deoxysphingoid bases with a saturated hydrocarbon sidechain such as spisulosine, xestoaminol C, 3-epi-xestoaminol C, clavaminol A have attracted considerable attention from synthetic organic chemists because of their impressive cytotoxic/antiproliferative properties as well as the unique structures possessing a variously configured vicinal amino alcohol motif.

Results: The stereoselective total synthesis of two deoxysphingosines ent-homospisulosine and N,Odiacetylhomoclavaminol A has been accomplished via a common approach. The key steps were a substrate controlled aza-Claisen rearrangement to install the C-N bond together with the required erythro arrangement of the neighbouring amino and hydroxyl functionalities. Further, the spontaneous intramolecular addition to the –NCS moiety proceeded regioselectively to form the requisite oxazolidine-2-thione skeleton. The employed Wittig olefination then completed the carbon backbone of the target molecules.

Conclusions: Several newly prepared compounds was assessed for their antiproliferative/cytotoxic activity against six cancer cell lines (Jurkat, HeLa, MDA-MB-231, MCF-7, HTC-116 and Caco-2) using the MTT assay. On the basis of the observed potency, three structures were taken up for further investigation.

Keywords: Deoxysphingoid bases, spisulosine, clavaminol A, [3, 3]-heterosigmatropic rearrangement, stereoselective synthesis, antiproliferative/cytotoxic activity.