Salinosporamide A (1) was isolated by Fenical and co-workers from the Salinospora strain CNB-392 of marine actinomycete bacteria. Salinosporamide A (1) is structurally related to omuralide (2), a highly potent and specific inhibitor of the 20S proteasome. The 20S proteasome is responsible for intracellular protein degradation and for controlling the levels of many regulatory proteins, including those involved within the cell cycle. Salinosporamide (1) shares with omuralide (2) a fused heterobicyclic ring structure, but differs in the side chains at C2, C3 and C5. As a result, 1 is approximately 35 times more potent than 2 towards 20S proteasome inhibition and, in addition, it displays surprisingly high in vitro cytotoxic activity against many tumor cell lines. Due to the impressive biological activity of 1, this compound has become an important target for the synthetic community. Our progress towards the synthesis of 1 will be presented.