Dictyodendrin alkaloids

Dictyodendrin alkaloids have been described as the first telomerase inhibitors of marine origin and hence represent potential lead compounds in the quest for small molecule inhibitors of the tumor-marker enzyme. In a 2009 study, Fiirstner et al. [58] reported the synthesis of several members of the series, making use of FI—HMBC data. 

P. Buchgraber, M.M. Domostoj, B. Scheiper, C. Wirtz, R. Mynott, J. Rust, A. Fiirstner, Synthesis-driven mapping of the dictyodendrin alkaloids. Tetrahedron 65 (2009) 6519-6534. 

The dictyodendrin class of carbazole alkaloids (see Schemes 2.70 and 2.71) completely inhibit telomerase activity (at a concentration of 50 pg/mL). It is known that 90% of human tumors show telomerase activity, which is absent in normal cells. Telemorase is a ribonucleoprotein enzyme that adds repeating known telomers to the DNA sequence (251). 

Funk and Huntley converted divinylpyrrolidine 10 to diene 11, and thence to an indole precursor 12 of )-cis-trikentrin B. A similar sequence was used to synthesize ( )-ci5 -trikentrin B. Dihydropyrrole 10 was assembled in five steps from A-Boc-2-pyrrolidinone. Fiirstner and coworkers synthesized several pyrrolo[2,3-c]carbazole alkaloids, the dictyodendrins B, C, and E, that featured a photochemical 6it-elecirocyclization and in situ dehydrogenation (equation 2) [21], Danheiser and colleagues effected an intramolecular benzyne generation and cycloaddition onto an alkynylpyrrole to afford a polycyclic indole (equation 3) [22],... 

In 2015, Yamaguchi, Itami, Davies, and coworkers accomplished the synthesis of dictyodendrins A and F, pyrrole-carbazole alkaloids, by catalytic C-H functionalization (Scheme 16.15 compare to Section 16.2.1.7) [32]. This synthesis also utilized a rhodium-catalyzed -selective C-H arylation of pyrroles with aryl iodides as the initial reaction. Pyrrole 84 was coupled with aryl iodide 85 in the presence of the same electron-deficient rhodium catalyst to afford... 

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