Pyrrolophenanthridone alkaloids

The short synthesis of the pyrrolophenanthridone alkaloid hippadine was accomplished by D.C. Harrowven and co-workers. " The key step of the synthetic sequence was the Ziegler modified intramolecular Ullmann biaryl coupling between two aryl bromides. One of the aryl halides was 7-bromoindole which was prepared using the Bartoli indole synthesis. The second aryl bromide was connected to 7-bromoindole via a simple A/-alkylation. 

Scheme 3. Direct, short and effective synthesis of pyrrolophenanthridone alkaloids...

Padwa and co-workers reported an approach to the pyrrolophenanthridone alkaloids (e.g., hippadine) that uses an intramolecular oxazole-alkyne Diels-Alder reaction. Thus the 2-acetamidooxazole model system 217 was thermolyzed at 200°C to produce the tricyclic furan 218 in 93% yield (Fig. 3.63). 

Miscellaneous Processes. A versatile synthetic route to the pyrrolophenanthridone alkaloids has been developed that involves a palladium-mediated cyclization of iV-benzoyl indolines, then 2,3-dichloro-5,6-dicyano- 1,4-benzoquinone (DDQ)-promoted oxidation of the resulting dihydropyrrolophenanthridones. Related processes have been exploited in an elegant total synthesis of the marine alkaloid (+)-dragmacidin F and in the preparation of biologically relevant indoles. 202.203... 

Anhydrolycorinone [55], Hippadine [56], Oxoassoanine [46], Pratosine [57]. The syntheses of alkaloids, incorporating the pyrrolophenanthridone nucleus, in the majority of cases followed the A + CD - AG) - ACDB sequence, in which organometallic chemistry featured prominently in this transformation. 

Lycorine-type alkaloids derived from pyrrolo[3,2,l-(ie] phenanthridine/ pyrrolophenanthridone ... 

Phenanthridinone derivatives have been reported to be found in a number of natural alkaloids and exhibit a wide range of biological activities. In the case of starting from bi-functionalized arenes with transition metal catalysts, the intramolecular cyclization of 2-bromo-iV-arylbenzamides via C-H activation is the most direct pathway, which has been applied in the synthesis of anti-hepatitis C virus agents and materials. Remarkably, Yao, Xu and their co-workers developed a one-pot procedure for the synthesis of a pyrrolophenanthridone skeleton via an intramolecular Heck reaction and oxidation of N-(2-bromobenzyl) substituted indoles. Moderate to good yields of the desired products were isolated in one step (Scheme 3.67). From the point view of academic interest, the... 

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