Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness.

Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp.

Synthetic Studies toward the Preparation of Phosphonate Analogs of Sphingomyelin and Ceramide 1-Phosphate Using Pentacovalent Organophospholene Methodology.

Model studies for the syntheses of phosphonate analogs of sphingomyelin and ceramide 1-phosphate are described. The pentacovalent oxaphospholene 3b (derived from methyl vinyl ketone and triethyl phosphite) readily condensed with dialkyl azodicarboxylates (R = Et, t-Bu, CH(2)CCl(3)) to form beta-hydrazido gamma-ketophosphonates 5 and 8 in excellent yields. Cleavage of the N-N bond in 5a (R = Et) or 5b (R = t-Bu) via standard methods was unsuccessful.