Beilstein Journal of Organic Chemistry2006, 2:1 doi:10.1186/1860-5397-2-1

Using new variations of anionic aromatic chemistry, the total synthesis of oxygenated brazanquinones (1a-1c), derived from β-brasan, a natural product isolated from Caesalpina echinata, via carbamates 2a-2c is described.


Introduction
The search for new synthetic routes for the total synthesis of biologically active natural products has been growing in recent years, often stimulated by the lack of synthetic drugs for the cure of diseases.
In various biological tests, several natural and synthetic brazanquinones have shown high biological activity. Cheng [1,2] in his work, evaluated (in vitro) a series of brazanquinones and their inhibitory activity against a series of cancer cell lines. Their activity has been attributed to their structure, in which the two ring systems are coplanar, and has attracted considerable attention as interesting synthetic targets. [3][4][5][6][7][8][9][10][11] However, the routes described in the literature do not offer the possibility of facile syntheses of other oxygenated analogues.
In this present work, the versatility of a new variation of anionic aromatic chemistry developed in our research group [12] will be applied in the context of rapid and efficient construction of these bioactive compounds for future biological evaluation.
Conceptual combination of path b and the well established tandem DoM route to anthraquinones and heteroanthraquinones [20] led to the conjecture that, barring the competitive [1,2]-Wittig rearrangement, and onepot route, 3 → 4 → 1, may be established in a direct manner without resort to DoM-derived benzamide intermediate, thereby establishing new carbonyl dianion equivalency 4 (see Scheme 1).
We now report the versatility of this strategy, in the context of rapid and efficient construction of new oxygenated brazanquinones (1a-1c) derived from β-brasan, a natural product isolated from Caesalpina echinata (Scheme 2).
The mechanism suggested by us and shown in scheme 1, involves first the preparation of aryllithium intermediates 3 from the carbamates 2a-2b by the reversible metathesis reaction known [21][22][23] as the lithium-halogen exchange which has been widely employed for replacement of a bromine or iodine atom in a substrate by lithium. The intermediate 3 then undergoes an intramolecular anionic Fries rearrangement to intermediate 4, that was isolated in our previous results. [12] Snieckus reported the remote metalation and cyclization of diethyl N-methyl-O-tolylanthranilamide to N-methyl dibenzazepinone [24][25][26] developing a new regiospecific construction of condensed aromatics. We found this route very attractive and envisaged that by in situ treatment of intermediate 4 with the third equivalent of sec-BuLi, the cyclization to the desired quinone 1a-d would be obtained.

Conclusion
An efficient synthesis of brazanquinones (1a-c) using new variations of anionic aromatic chemistry was described. This methodology could be expanded in the future for the construction of new molecules with similar structures.