Synthesis of C(11)N(5) Marine Sponge Alkaloids: (+/-)-Hymenin, Stevensine, Hymenialdisine, and Debromohymenialdisine.
The synthesis of C(11)N(5) marine sponge alkaloids (+/-)-hymenin (1), stevensine (2), hymenialdisine (3), and debromohymenialdisine (4) is described. These natural products are the primary family members of the sponge metabolites that contain a fused pyrrolo[2,3-c]azepin-8-one ring system with either a 2-aminoimidazole (AI) or glycocyamidine appendage. The key steps in the synthesis centered around the generation of novel azafulvenium ions and their regioselective heterodimerization with AI in order to create the tricyclic core. A rarely used protodebromination/oxidation strategy was employed to selectively generate the desired alpha-bromo substitution pattern seen in hymenialdisine (3). In addition, the AI moiety was shown to be a useful precursor to the glycocyamidine unit found in 3 and 4, which suggests that AI-derived natural products may be the biogenic forerunners to glycocyamidine metabolites.
Xu Yz
Ying-zi
Department of Chemistry, Columbia University, New York, New York 10027.
Yakushijin
Kenichi
K
Horne
David A.
DA