Croomine is a representative member of the Stemona class of alkaloids. These novel polycyclic natural products were isolated from medicinal plants used extensively in traditional East Asian medicine as antitussive and antituburcular agents. In addition to their medicinal uses, the Stemona alkaloids have recently attracted attention for their potent insecticidal activity. Notably, the structures of most members of this class of natural products are characterized by a common pyrrolidinyl butyrolactone core. An enantioselective method of accessing this structural motif via a catalytic vinylogous Mannich reaction has been proposed. This research plan relies on the ability of Jacobsen's recently developed non-metal catalyst for the Strecker reaction to activate imines towards nucleophilic attack. The addition of electron-rich 2-silyloxyfurans to the imine-catalyst complex is expected to occur with high levels of enantio- and diastereoselectivity. Optimization of the catalyst structure for this transformation will be performed by combinatorial synthesis of a small, """"""""focused"""""""" library of catalyst analogs. After exploring the substrate scope of this new reaction, the synthetic utility of the enantioselective vinylogous Mannich will be demonstrated in a concise total synthesis of (+)-croomine (7 steps, best case).

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32GM066483-01
Application #
6551093
Study Section
Special Emphasis Panel (ZRG1-F04 (20))
Program Officer
Marino, Pamela
Project Start
2002-08-01
Project End
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
1
Fiscal Year
2002
Total Cost
$36,592
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