Compounds having the ability to interfere with microtubule mediated functions in the cell have become of recent interest as therapeutic agents, tools to probe the machinery of the cell,, as synthetic targets. The successful use of compounds in chemotherapeutic regiments, like Taxol, illustrate the medical importance of cytotoxic agents capable of interrupting the cellular role of microtubules. Ustiloxin A is a new member of this class of compounds that presents some interesting synthetic challenges. It is the goal of the proposed research to complete the total synthesis of ustiloxin A. In doing so, the synthesis of this unique 13 membered cyclic peptide will address some interesting bond constructions. The first of which is the asymmetric synthesis of a tertiary beta-aryloxy-alpha-amino acid utilizing a sequential asymmetric alkylation and reduction sequence. The second challenge to be addressed is the construction of a beta-hydroxy-alpha-amino acid by the asymmetric glycinamide aldol condensation with the requisite aldehyde. The purpose of this proposal will be to outline a concise synthetic plan to oxygenated alpha-amino acids and apply those proposed methods to the synthesis of ustiloxin A.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32CA083255-02
Application #
6342176
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Lohrey, Nancy
Project Start
2000-12-09
Project End
Budget Start
2000-12-27
Budget End
2001-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$20,965
Indirect Cost
Name
Harvard University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138