Total Synthesis of Teleocidins B

Total Synthesis of Teleocidins B

Author: ChemistryViews.org

Teleocidins B-1 through B-4 (B−4 pictured) are a family of natural products which were isolated from Streptomyces mecliocidius. The compounds are indole-alkaloids and can activate the enzyme protein kinase-C (PKC). The four different members differ in the configurations at two stereocenters (C19 and C22). Syntheses for teleocidins B-3 and B-4 reported so far require 17−28 steps.

Phil S. Baran and colleagues, The Scripps Research Institute, La Jolla, CA, USA, have developed a simple, eleven-step synthesis of teleocidins B-1 through B-4. The team started from commercially available 4-bromoindole. They used an electrochemical aryl amination at C4 and a Cu-mediated tryptophol construction at C3, followed by a macrolactonization to prepare indolactam V as a key intermediate. This five-step synthesis is the shortest path to indolactam V reported so far. 

A C−H borylation allowed the researchers to functionalize the indole at C6. At this point, the synthesis diverges based on the desired product stereoisomer. The team used a stereocontrolled quaternary center formation via a Sigman−Heck reaction to prepare intermediates with the desired configuration at C19. Finally, an addition of vinyllithium followed by a ring closure gave all four desired products.



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