The proposed research outlines a general method for the synthesis of the batzelladine alkaloids recently isolated from the Caribbean sponge Batzella sp. The general method is exemplified by the synthesis of batzelladine A. The synthesis is easily broken into two sizable portions. One of fragments resembles an intermediate in a successful synthesis of (-)saxitoxin, and established methods will be employed. The other piece is a fused tricyclic guanidinium unit, and this portion will be prepared by employing a modification of the recently described tethered Biginelli reaction. Stereochemical issues will be addressed in a straightforward manner, as established methods and geometric restrictions will be relied upon. As the batzelladines show toxicity against proliferating Vero cells as well as inhibition of some substrate enzyme binding, they are expected to be of interest therapeutically. The described methods could provide significant quantities of batzelladines for clinical testing as well provide the potential for the preparation of analogs which may have even greater biological activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM018010-02
Application #
2331932
Study Section
Medicinal Chemistry Study Section (MCHA)
Project Start
1997-01-22
Project End
Budget Start
1997-01-22
Budget End
1998-01-21
Support Year
2
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of California Irvine
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Irvine
State
CA
Country
United States
Zip Code
92697