Anne Jäger

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.

Snapshot of the palladium(II)-catalyzed oxidative biaryl bond formation by X-ray analysis of the intermediate diaryl palladium(II) complex.

Pd(II) caught in the act: The diaryl Pd(II) intermediate of a Pd(II)-catalyzed oxidative biaryl bond formation proceeding via a double C-H bond activation has been isolated and fully characterized, including an X-ray crystal structure analysis. Stabilization due to chelation by adjacent pivaloyloxy and acetyl groups has allowed the isolation of this long-sought crucial intermediate. On gentle warming, the complex is transformed into a carbazole product, and the catalytically active Pd(II) species is regenerated by oxidation with Cu(II).

First total synthesis of the whole series of the antiostatins A and B

The first synthesis of the whole antiostatin family is described by using an iron-mediated carbazole synthesis, regioselective nitration at C-4 and establishing 5-isobutyl-1-nitrobiuret as a reagent for introduction of the antiostatin B side chain at C-4.

Efficient iron-mediated approach to pyrano[3,2-a]carbazole alkaloids—first total syntheses of O-methylmurrayamine A and 7-methoxymurrayacine, first asymmetric synthesis and assignment of the absolute configuration of (−)-trans-dihydroxygirinimbine

Iron-mediated oxidative cyclisation provides an efficient approach to pyrano[3,2-a]carbazole alkaloids. Thus, improved routes to girinimbine and murrayacine as well as the first total syntheses of O-methylmurrayamine A and 7-methoxymurrayacine are reported. Asymmetric epoxidation of girinimbine led to (-)-trans-dihydroxygirinimbine and the assignment of its absolute configuration.

Interaction of an extended series of N-substituted di(2-picolyl)amine derivatives with copper(II). Synthetic, structural, magnetic and solution studies

The interaction of Cu(II) with the following secondary N-substituted derivatives of di(2-picolyl)amine () are reported: N-cyclohexylmethyl-di(2-picolyl)amine (), N-benzyl-di(2-picolyl)amine (), N-(4-pyridylmethyl)-di(2-picolyl)amine (), N-(4-carboxymethylbenzyl)-di(2-picolyl)amine (), N-(9-anthracen-8-ylmethyl)-di(2-picolyl)amine (), 1,3-bis[di(2-picolyl)aminomethyl]benzene (), 1,4-bis[di(2-picolyl)aminomethyl]benzene () and 2,4,6-tris[di(2-picolyl)amino]triazine (). The solid complexes [Cu()(micro-Cl)](2)(PF(6))(2), [Cu()(micro-Cl)](2)(PF(6))(2).0.5CH(2)Cl(2), Cu()(ClO(4))(2), Cu()(2)(ClO(4))(2), [Cu()(ClO(4))(2)(H(2)O)].0.5H(2)O, Cu(2)()(ClO(4))(4), [Cu(2)()(Cl)(4)] and [Cu(2)(+H)(micro-OCH(3))(2)(H(2)O)](ClO(4))(3).C(4)H(10)O were isolated and X-ray structures of [Cu()(micro-Cl)](2)(PF(6))(2), [Cu()(micro-Cl)](2)(PF(6))(2).0.5CH(2)Cl(2,) [Cu()(2)(ClO(4))(2)(H(2)O)].0.5H(2)O, [Cu(2)()Cl(4)] and [Cu(2)(+H)(micro-OCH(3))(2)(H(2)O)](ClO(4))(3).C(4)H(10)O were obtained. The series is characterised by a varied range of coordination geometries and lattice architectures which in the case of [Cu()(ClO(4))(2)(H(2)O)].0.5H(2)O includes a chain-like structure formed by unusual intermolecular pi-interactions between metal bound perchlorate anions and the aromatic rings of adjacent anthracenyl groups. Variable temperature magnetic susceptibility measurements have been performed for [Cu()(micro-Cl)](2)(PF(6))(2) and [Cu()(micro-Cl)](2)(PF(6))(2).0.5H(2)O over the range 2-300 K. Both compounds show Curie-Weiss behaviour, with the data indicating weak antiferromagnetic interaction between the pairs of copper ions in each complex. Liquid-liquid (H(2)O/CHCl(3)) extraction experiments involving and as extractants showed that, relative to the parent (unsubstituted) dipic ligand , substitution at the secondary amine site in each case resulted in an increase in extraction efficiency towards Cu(II) (as its perchlorate salt); at least in part, this increase may be attributed to the enhanced lipophilicities of the N-substituted derivatives.

Total syntheses of murrayamine E, I, and K.

We describe efficient synthetic routes to murrayamine A (mukoenine C), O-methylmurrayamine A, mahanine, O-methylmahanine, and murrayamine D and the first total syntheses of murrayamine E, I, and K. Key steps are a palladium-catalyzed construction of the carbazole framework and an annulation of the pyran ring, which is either catalyzed by phenylboronic acid or promoted by a Lewis acid.

A practical access to highly enantiomerically pure flavanones by catalytic asymmetric transfer hydrogenation.

A surprisingly selective, non-enzymatic kinetic resolution of readily available, racemic β-chiral ketones enabled the title process, which was applied to a rapid synthesis of several bioactive flavanones in virtually enantiopure form (see scheme; MOM=methoxymethyl, Ts=p-toluenesulfonyl).

Investigations of peptides and proteases in green coffee beans

Cof. canephora var. robusta. The coffee types were not significantly different in peptide content, but were significantly different in peptide composition. Peptides with weakly acid pI values were mainly found in the Cof. robusta samples. In comparison, peptides from Cof. arabica samples ranged evenly from the weakly acidic up to the weakly basic pH range. The apparent molecular masses of the peptides in the two groups of samples lie between 4 kDa and 10 kDa. The cysteine content of the peptides was relatively high. Model roastings permitted the assumption that peptides make a contribution to coffee flavour. Peptides are already available in freshly harvested coffee. Model tests have suggested that processing after the coffee harvest has an influence on peptide composition but not on the amounts of peptide. All coffee samples contained some extractable proteases. The electrophoretically obtained enzyme patterns of Cof. arabica and Cof. robusta were different.

Synthesis of Glycoborine, Glybomine A and B, the Phytoalexin Carbalexin A and the β‐Adrenoreceptor Antagonists Carazolol and Carvedilol

We describe a regioselective synthesis of 4- or 5-substituted carbazoles by oxidative cyclisation of meta-oxygen-substituted N-phenylanilines. Using the regiodirecting effect of a pivaloyloxy group, we prepared 4-hydroxycarbazole, a precursor for the enantiospecific synthesis of the β-adrenoreceptor antagonists (-)-(S)-carazolol (5) and (-)-(S)-carvedilol (6). Regioselective palladium(II)-catalysed cyclisation of different diarylamines led to total synthesis of glycoborine (7) and the first total syntheses of the phytoalexin carbalexin A (8), glybomine A (9) and glybomine B (10). For glybomine B (10), a 5-hydroxycarbazole was converted into the corresponding triflate and utilized for introduction of a prenyl substituent.