O. N. Kataeva

Efficient Construction of Pyrano[3,2-a]carbazoles: Application to a Biomimetic Total Synthesis of Cyclized Monoterpenoid Pyrano[3,2-a]carbazole Alkaloids†

We have developed a highly efficient route to 2-hydroxy-3-methylcarbazole (1) via a palladium-catalyzed construction of the carbazole skeleton. Using 1 as relay compound, different methods for annulations of pyran rings by reaction with terpenoid building blocks have been tested. The Lewis acid promoted reaction of 1 with prenal (21) opened up an efficient route to girinimbine (3) and the corresponding reaction with citral (25) afforded mahanimbine (5). Oxidation of compounds 3 and 5 provided murrayacine (4) and murrayacinine (6). Following the biogenetic proposal, mahanimbine (5) has been exploited for efficient biomimetic syntheses of the cyclized monoterpenoid pyrano[3,2-a]carbazole alkaloids cyclomahanimbine (7), mahanimbidine (8) and bicyclomahanimbine (9). The interconversions of 5, 7, 8 and 9 are described and mechanistic implications are discussed. Structural assignments are unambiguously verified by X-ray crystal structure determinations. Moreover, cyclomahanimbine (7) was transformed into murrayazolinine (10) and exozoline (11).

Total Synthesis of the Biscarbazole Alkaloids Murrafoline A–D by a Domino Sonogashira Coupling/Claisen Rearrangement/Electrocyclization Reaction†

Why take things one step at a time? Aryl-pyran-linked biscarbazole alkaloids of the murrafoline group (see crystal structure of murrafoline A; dark gray: C, red: O, blue: N) were accessed readily by a novel domino reaction sequence involving Sonogashira coupling, a Claisen rearrangement, and electrocyclization. The one-pot procedure enables the straightforward synthesis of these structurally challenging alkaloids in only a few steps.

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).

Microwave-mediated Regioselective Synthesis of Novel Pyrimido(1,2-a)pyrimidines under Solvent-free Conditions

Abstract Ethyl 2-amino-4-aryl-1,4-dihydro-6-phenylpyrimidine-5-carboxylates readily react, under microwave irradiation and solvent-free conditions, with 3-formylchromone or diethyl (ethoxymethylene)malonate to yield novel pyrimido[1,2-a]pyrimidines. The structure of the final products, deduced from the spectral data and confirmed by X-ray analysis, allows us to suggest reaction pathways.

Total Synthesis of 7‐ and 8‐Oxygenated Pyrano[3,2‐a]carbazole and Pyrano[2,3‐a]carbazole Alkaloids via Boronic Acid‐Catalyzed Annulation of the Pyran Ring

The boronic acid-catalyzed annulation of citral opens up a short route to oxygenated cyclized monoterpenoid pyranocarbazole alkaloids. Thus, murrayamine-D is available in only three steps and 55% overall yield from the corresponding carbazole precursor.

Synthesis of Prenyl- and Geranyl-Substituted Carbazole Alkaloids by DIBAL-H Promoted Reductive Pyran Ring Opening of Dialkylpyrano[3,2-a]carbazoles†

The DIBAL-H promoted reductive pyran ring opening of dialkylpyrano[3,2-a]carbazoles provides a direct access to a broad range of prenyl- and geranyl-substituted carbazoles. Formation of a pyran ring followed by reductive ring opening represents a new method for the introduction of prenyl and geranyl groups. In the course of the present work, we achieved the first total syntheses of the following eight carbazole alkaloids: clauraila-E, 7-hydroxyheptaphylline, 7-methoxyheptaphylline, mukoenine-B (clausenatine-A), mukoenine-A (girinimbilol), mahanimbinol (mahanimbilol), euchrestine-A, and isomurrayafoline-B.

Self-assembling systems based on amphiphilic alkyltriphenylphosphonium bromides: Elucidation of the role of head group

A systematic study of the aggregation behavior of alkyltriphenylphosphonium bromides (TPPB-n; n=8, 10, 12, 14, 16, 18; here n is the number of carbon atoms in alkyl groups) in aqueous solutions has been carried out and compared with trimethyl ammonium bromides (TMAB-n). Critical micelle concentrations (cmcs) of TPPB-n and TMAB-n decrease with the number of carbon atoms with the slope parameter of ca.0.3. The low cmcs and effective solubilization power toward Orange OT indicate high micellization capacity of phosphonium surfactants. The low counterion binding parameter β is revealed for TPPB-10 and TPPB-12, while high counterion binding of ≥80% is observed for high TPPB-n homologs. Values of the surface potential ψ calculated on the basis of pK(a) shifts of p-nitrophenols is similar for both series and monotonously increase with alkyl chain length. Several points indicate non-monotonic changes within TPPB-n series. There are peculiarities of the tensiometry and solubilization plots for high homologs and above mentioned increases in counterion binding on transiting from low to high molecular weight surfactants. Differences in aggregation behavior between TPPB and TMAB series and between low and high homologs can be due to the specific structural character of the TPP(+) cation, which is supported by X-ray data.

1‐(α‐Aminobenzyl)‐2‐naphthol: A New Chiral Auxiliary for the Synthesis of Enantiopure α‐Aminophosphonic Acids

A new diastereoselective synthesis of alpha-aminophosphonates has been developed, based on the reaction, in the presence of trifluoroacetic acid, of trialkyl phosphites with chiral imines derived from (R)- or (S)-1-(alpha-aminobenzyl)-2-naphthol. The reaction proceeds at room temperature in toluene with high diastereoselectivity. The major diastereomer can be separated by crystallization from an appropriate solvent. The relative configuration of both chiral centers of the major diastereomer was determined by single-crystal X-ray structure analysis. The desired alpha-aminophosphonic acids can be obtained in enantiopure form by treatment of the corresponding diastereomers with HCl.

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.

Mechanistic study on the opposite migration order of the enantiomers of ketamine with α- and β-cyclodextrin in capillary electrophoresis

The enantiomer migration order of the chiral anaesthetic drug ketamine [RS-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone] was studied by capillary electrophoresis using various cyclodextrins as chiral selectors. The opposite migration order of the enantiomers of ketamine was observed when native α- and β-cyclodextrins were used as chiral selectors in capillary electrophoresis. The possible mechanisms of the opposite enantiomer migration order were investigated by employing electrospray ionization mass spectrometry, 1 H-NMR spectrometry, one dimensional rotating frame nuclear Overhauser and exchange spectroscopy, X-ray crystallography, and molecular modeling techniques. As this study indicates, capillary electrophoresis can be used as a reliable experimental technique for examination of the correctness of the results of molecular modeling calculations. In addition, based on X-ray crystallographic analysis it was confirmed that (-)-ketamine as a free base possesses S configuration.