Sporidesmins are a class of molecules that have been shown to be incredibly biologically active, several of which possess strong antibacterial or cytotoxic activity. Recently, chetomin has been shown to disrupt the interaction of hypoxia-inducible factor 1 (HIF-1) with its cognate transcriptional coactivator, p300/CBP. In cells and tissues, interaction of these two proteins leads to the overexpression of vascular endothelial growth factor (VEGF), which is essential for growth and metastasis of solid tumors. It has been suggested that chetomin, through its ability to disrupt the hypoxia-inducible transcription of VEGF, has the potential for therapeutic use. We plan to develop the synthetic approach to chetomin, along with the synthesis of a sporidesmins in optically active form. Toward this goal, we are developing enantioselective organocatalytic α-sulfenylation of diketopiperazines as a route to optically active sporidesmins, including chetomin.