OPTIMIZATION OF SCALE-UP SYNTHESIS OF ANTI-CANCER CERAMIDE ANALOG 315.

Ceramides, serve as central mediators in sphingolipid metabolism and signaling pathways. They function in signaling events which induce apoptosis, cell cycle arrest, and autophagic responses. In cancer cells, ceramide levels are often suppressed by the up-regulation of ceramide-metabolizing enzymes or the down-regulation of ceramide-generating enzymes, resulting in increased cancer cell survival. Chemotherapeutic drugs and radiation therapy have been shown to increase intracellular ceramide levels leading to anti-cancer effects. Anti-cancer effects have also been seen in cancer cells with the use of exogenous short-chain ceramides. Our laboratory has synthesized a library of ceramide analogs and tested their effects on breast cancer cell lines. Analog 315 has been shown to be the most effective ceramide analog in our library. Here, we are reporting a large-scale synthesis of that analog is reported.