Total Synthesis of (+/-)-Hinckdentine A

Abstract

Hinckdentine A (1) was isolated from the bryozoans Hincksinoflustra denticulate living in the eastern coast of Tasmania. Its structure and absolute configulation were determined by single-crystal X-ray analysis. Hinckdentine A (1) has a unique architecture containing of seven -membered lactam ring fused to the tribromoindolo[1,2-c]quinazoline with a quaternary carbon center. The framework of 1 consists of biologically important dihydrotryptamine and dihydropyrimidine units together with cataleptically active indolo[1,2-c]quinazoline core, though the biological activity of 1 has not appeared in the literature.
We have accomplished the first total synthesis of (+/-)-hinckdentine A (1). The key steps are m-CPBA oxidation of 2-arylindole followed by acid-mediated Mannich-type C-C bond formation of 2-hydroxyindolin-3-one, seven-membered ring closure and regioselective tribromination.