The first total synthesis of the alkaloid pityriazole is described using three consecutive palladium-catalyzed coupling reactions.

A series of carbazole derivatives with promising pharmacological properties has been prepared using either an iron-mediated or a palladium-catalyzed synthetic approach. The carbazole alkaloids carbazoquinocin C, carbazomadurin A and B, epocarbazolin A and B, neocarazostatin B, and carquinostatin A are antioxidants acting as free-radical scavengers. Thus, they represent potential lead compounds for the development of novel drugs against diseases initiated by oxygenderived free radicals. Initiated by the first naturally occurring carbazole alkaloids with antituberculosis (anti-TB) activity, clausine K and micromeline, a study on the structure-activity relationships for anti-TB-active carbazole derivatives has been carried out. The 6-oxygenated carbazoles glycozoline and glycozolinine show antibiotic activity towards several microorganisms. The 7-oxygenated carbazole siamenol exhibits anti-HIV activity.

We have developed efficient synthetic routes to heterocyclic ring systems using transition metals (palladium, iron, and silver). Recent applications of this chemistry to the total synthesis of biologically active alkaloids include carbazole alkaloids (pityriazole, euchrestifoline, the antiostatins), crispine A, pentabromo-and pentachloropseudilin. The two latter alkaloids represent a novel class of myosin ATPase inhibitors that led to the discovery of a new allosteric binding site of the protein.

The palladium(0)-catalyzed amination followed by palladium(II)-catalyzed oxidative cyclization of the resulting diarylamine provides a short route to a series of 6-oxygenated carbazole alkaloids: glycozoline, 3-formyl-6-methoxycarbazole, methyl 6methoxycarbazole-3-carboxylate, glycozolinine (glycozolinol), glycomaurrol, micromeline, and eustifoline-D.

P a l l a d i u m -C a t a l y z e d R o u t e t o 2 -O x y g e n a t e d a n d 2 , 7 -D i o x y g e n a t e d C a r b a z o l e A l k a l o i d s Abstract: Optimization of the palladium(II)-catalyzed oxidative cyclization of N,N-diarylamines opens up the way to an efficient synthesis of 2-oxygenated and 2,7-dioxygenated carbazole alkaloids including 2-methoxy-3-methylcarbazole, glycosinine, clausine L, mukonidine, and clausine V.