Micha P. Krahl

Synthesis and activity of carbazole derivatives against Mycobacterium tuberculosis

Infecting one-third of the world’s inhabitants, Mycobacterium tuberculosis (MTB) is deemed a serious public health concern. Failure to follow the current regimen along with the HIV pandemic have led to the emergence of multiple drug-resistant tuberculosis (MDR-TB) strains. The pursuit of more efficacious drugs and prophylaxis is warranted. Findings of some naturally occurring carbazole alkaloids (Figure 1), exhibiting antituberculosis activity, have prompted us to explore further carbazole derivatives for structure–activity relationships. Clausine K or clauszoline J, a natural product isolated independently from several sources, was found to have weak antituberculosis activity (MIC of 100 mgmL 1 against the H37Ra strain). Ma et al. isolated micromeline from the stem bark of Micromelum hirsutum along with some known carbazole alkaloids, and found the MIC to be 31.5 mgmL 1 against M. tuberculosis H37Rv (selectivity index >3). [8] Based on these findings, we screened a series of carbazole alkaloids and derivatives for their in vitro anti-TB activity to find out whether the carbazole framework represents a novel antituberculosis scaffold. The intention of the present study was to identify potent anti-TB active carbazoles and to establish preliminary structure–activity relationships (SAR). Compounds 4a–i were purchased from Sigma Aldrich; 4 j–v and 8–15 were prepared using either the iron-mediated or the palladium-catalyzed approach previously developed by our group (Schemes 1 and 2, Table 1). An electrophilic aromatic substitution of the tricarbonyliron-cyclohexadienylium salts 1 and the arylamines 2 affords functionalized tricarbonyliron complexes 3. The oxidative cyclization of the tricarbonyliron complexes 3 furnishes substituted carbazole derivatives 4. In another approach, the palladium(0)-catalyzed amination of aryl

First total synthesis of the 7-oxygenated carbazole alkaloids clauszoline-K, 3-formyl-7-hydroxycarbazole, clausine M, clausine N and the anti-HIV active siamenol using a highly efficient palladium-catalyzed approach

Using a convergent palladium-catalyzed construction of the carbazole framework as the key step we have achieved a short synthesis of the 7-oxygenated carbazole alkaloids clauszoline-K, 3-formyl-7-hydroxycarbazole, clausine C (clauszoline-L), clausine M, clausine N and the anti-HIV active siamenol.

Transition metals in organic synthesis - Part 83#: Synthesis and pharmacological potential of carbazoles

A series of carbazole derivatives with promising pharmacological properties has been prepared using either an iron-mediated or a palladium-catalyzed synthetic approach. The carbazole alkaloids carbazoquinocin C, carbazomadurin A and B, epocarbazolin A and B, neocarazostatin B, and carquinostatin A are antioxidants acting as free-radical scavengers. Thus, they represent potential lead compounds for the development of novel drugs against diseases initiated by oxygen-derived free radicals. Initiated by the first naturally occurring carbazole alkaloids with antituberculosis (anti-TB) activity, clausine K and micromeline, a study on the structure–activity relationships for anti-TB-active carbazole derivatives has been carried out. The 6-oxygenated carbazoles glycozoline and glycozolinine show antibiotic activity towards several microorganisms. The 7-oxygenated carbazole siamenol exhibits anti-HIV activity.

First total synthesis of the biscarbazole alkaloid oxydimurrayafoline

We report the first total synthesis of oxydimurrayafoline via nucleophilic substitution at the benzylic position at C-3 of the carbazole framework.

CCDC 988854: Experimental Crystal Structure Determination

Related Article: Ronny Hesse, Micha P. Krahl, Anne Jager, Olga Kataeva, Arndt W. Schmidt, Hans-Joachim Knolker|2014|Eur.J.Org.Chem.||4014|doi:10.1002/ejoc.201402201