The proposed synthesis of pseudopterolide addresses several meaningful scientific issues. Pseudopterolide is a natural product with particularly interesting biological activity. It disrupts cell division via a selective mechanism and is cytotoxic at concentrations of 1-10 muo1/M. The highlight of the proposed synthesis is the implementation of an enyne metathesis reaction that should allow the conversion of a cyclophane into the desired strained ring system in one efficient step. One of the goals of the synthesis is to broaden the scope of this metathesis by subjecting new types of substrates to the reaction conditions. This ring-expanding enyne metathesis forms the basis for the assembly of a large ring with several stereocenters, constituting a new synthetic approach to the pseudopterane natural products. Other interesting steps in the proposed route include the diasteroselective macrocyclization of a trichloroallylsilane, an unusual epoxidation sequence, and a stereo- and regioselective coupling reaction proceeding through an apparent pi-allyl nickel complex. Taken together, the chemistry that will be explored over the course of this research will be illuminating, efficient. and most importantly, should result in discoveries that will help to expand the frontiers of synthetic chemistry.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM020234-02
Application #
6385108
Study Section
Medicinal Chemistry Study Section (MCHA)
Program Officer
Ikeda, Richard A
Project Start
2001-04-24
Project End
Budget Start
2001-04-24
Budget End
2001-11-30
Support Year
2
Fiscal Year
2001
Total Cost
$22,982
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