The trikentrin and herbindole alkaloids are two groups of poly-alkylated indole natural products that have been isolated from marine sponges. Both groups have exhibited interesting biological activities such as antimicrobial, cytotoxic, and antifeedant activity. These molecules are structurally unique compared to currently marketed antimicrobials, so synthesis of these molecules and their analogues may provide a new chemical scaffold for novel antimicrobials. In our approach to this family of natural products, we construct a meso-symmetric hydroquinone using a ruthenium-catalyzed [2+2+1+1] cycloaddition. The meso-hydroquinone is then desymmetrized through activation and subsequent cross-coupling. A second cross-coupling with an ammonia equivalent affords an ortho-ethylaniline compound. From this ortho-ethylaniline derivative, we are investigating methods for formation of the desired C�N bond to construct the indole unit present in these natural products. This approach should enable a divergent synthesis of trikentrins, herbindoles, and derivatives thereof through a common hydroquinone intermediate. This synthesis will exploit the s element of symmetry present in the hydroquinone intermediate as well as explore new methods for C�N bond formation.

Meso-desymmetrization approach toward the total synthesis of cis-trikentrin A and herbindole B

248th National Meeting (2014)

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