The initial goal of the proposal is the development of an enantioselective hypervalent silicon mediated acyloin rearrangement (1 to 2) utilizing chiral ureas to promote the reaction. Upon realization of the first goal, the total synthesis of novel analog 3 of the selective phosphodiesterase 2 a (PP2a) inhibitors, fostriecin (IC50=40 Nm) and phoslactomycin F (ic50=4,7 muM) will be pursued utilizing the proposed methodology. The inhibition of PP2a has been reported to account for the potent anti-tumor activity of fastriecin against leukemia cells (I50=0.46 muM). The synthesis of 3 would provide insight into the differences in biological activities of the parent compounds, fostriecin, the phoslactomycins, and the leustroducsins. While this proposal will focus on the synthesis of analog 3, the synthesis is flexible thus allowing for future total syntheses of the parent natural products in addition to other analogs.
