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.
