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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32CA089898-01
Application #
6293450
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Lohrey, Nancy
Project Start
2001-08-23
Project End
Budget Start
2001-08-23
Budget End
2002-02-25
Support Year
1
Fiscal Year
2001
Total Cost
$33,260
Indirect Cost
Name
Stanford University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305