The main line of research in cancer treatment is the development of methods for early diagnosis and targeted drug delivery to cancer cells. Fluorescent semiconductor core/shell nanocrystals of quantum dots (e.g., CdSe/ZnS) conjugated with an anticancer drug, e.g., an acridine derivative, allow real-time tracking and control of the process of the drug delivery to tumors. However, linking of acridine derivatives to a quantum dot can be accompanied by quantum dot fluorescence quenching caused by electron transfer from the quantum dot to the organic molecule. In this work, it has been shown that the structure of the shell of the quantum dot plays the decisive role in the process of photoinduced charge transfer from the quantum dot to the acridine ligand, which is responsible for fluorescence quenching. It has been shown that multicomponent ZnS/CdS/ZnS shells of CdSe cores of quantum dots, which have a relatively small thickness, make it possible to significantly suppress a decrease in the quantum yield of fluorescence of quantum dots as compared to both the classical ZnS thin shell and superthick shells of the same composition. Thus, core/multicomponent shell CdSe/ZnS/CdS/ZnS quantum dots can be used as optimal fluorescent probes for the development of systems for diagnosis and treatment of cancer with the use of anticancer compounds based on acridine derivatives.

For the direct separation of enantiomers of tryptophan analogs, a native α -cyclodextrin-based Cyclobond III chiral stationary phase was examined. The separation conditions were optimized by variation of the different chromatographic parameters, and data are reported as retention factors, separation factors and resolutions. The nature and concentration of the buffers as mobile phase additivies exerted only slight effects on the retention and resolution. In all cases, the erythro isomers could be separated significantly better than the threo ones. With increasing hydrophobicity of the analytes, the retention time increased, but no clear trend could be observed between the resolution and the hydrophobicity. The sequence of elution of the enantiomers was in most cases determined by spiking the racemic samples with enantiorich analytes.

‘Bended’ 1, 3 or ‘linear’ 2 pyrrolidino-fused (aza)carbazoles were prepared and screened towards a few cancer-related targets. Whereas ‘bended’ derivatives 1 and 3 proved to be weakly toxic, several members of the ‘linear’ family strongly interact with DNA, especially derivative 28a.

A diastereoselective synthesis, using the Yonemitsu-type trimolecular condensation as the key step, has been used for the preparation of 3,4-heterocycle(furanone-, pyrrolidinone- and pyranone-) annulated tetrahydro-β-carbolines. The chirality of d-glyceraldehyde or that of the Garner’s aldehyde ensured a high and predictable diastereocontrol of the additional newly created stereocentres.

An access to functionalised tetrahydrocarbazoles by a multicomponent reaction including 2-substituted indoles, aromatic aldehydes and Meldrum's acid is described. (C) 2003 Elsevier Ltd. All rights reserved.

The direct cycloaddition of a N-methyl-3-cyanomethyl-2-vinylindole (1) with a N-methylmaleimide (2) is not observed. The in situ formation of an indolo-2,3-quinodimethane intermediate (3) leads instead of the normal cycloadduct to an 1,2,3,4-tetrahydrocarbazole (5). To help our understanding of this reaction, we performed a DFT study. The formation of both, the direct cycloadduct (4) and the intermediate (3) are found to be not thermodynamically favorable. However, the small amount of 3 formed in the medium reacts with the dienophile in this way explaining the regio-selectivity of the reaction. The diastereo-selectivity is finally explained by a Curtin–Hammett-type energy profile.

This short review offers a non-exhaustive panorama of the indole ring implicated multicomponent reactions, and simple functional group transformation-based approaches, developed over the last thirty years for the synthesis of various biologically interesting indole heterocyclic ring systems.

Chiral pyrano- and pyrrolidino-fused tryptamines were prepared by a diasteroselective trimolecular condensation between indole, Garner's aldehyde and Meldrum's acid, followed by selective functional group transformations.

We have developed a general, multicomponent reaction and selective functional group transformations based approach for the synthesis of non-natural tryptophan, tryptamine and tetrahydro-beta-carboline derivatives. This review covers our results during the period 1994-2002, including the use of chiral aldehydes.

2-Aminopropyl-3-indole acetic(propionic) acid derivatives have been prepared and characterised starting from 3-[(3-methoxycarbonylmethyl)-indol-2-yl] propionic acid methyl ester by means of chemoselective functional group manipulations.

Hydroxyalkylindolyl acetic (propanoic) acids 1 and 2 were prepared from a common intermediate dimethyl ester 3 by chemoselective hydrolyses and reductions.

Electron-donating substituted 3-cyanomethyl-2-vinylindoles were found to rearrange via thermal [1,5]H shift into the corresponding indole-2,3-quinodimethanes which were trapped by dienophiles to afford tetrahydrocarbazoles.

Trimolecular adducts resulting from condensation between indolin-2-one (or indoline-2-thione), (aryl)aldehydes, and Meldrum's acid are useful intermediates for the synthesis of either 1,2,3,4-tetrahydro-1-thiacarbazoles or spiro[pyrrolidino-3,3'-oxindoles] related to the natural product horsfiline. These latter compounds were obtained in a three-step procedure characterized by acyl azide formation, Curtius rearrangement, and subsequent thermal spiro cyclization. The relative stereochemistry of the spiro derivatives was determined by comparison of NOESY data and calculated conformational analyses. (C) Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002.

Ten bis-beta-carboline 1 , 2 and bis-3,4-dihydro-beta-carboline 3 , 4 derivatives, linked between carbons 1 and 1' by a polymethylene spacer, were synthesized from bis-tryptamine amides 9, 10 . Some of them display a micromolar IC50 towards L-1210 cells.

2-Substituted indoles were reacted with benzaldehyde, Meldrum's acid and triethylamine, to give a trimolecular adduct, further leading to spiro[pyrrolidinon-3,3′-indoles].

Direct high-performance liquid chromatographic chiral separation of numerous underivatized unnatural amino acids on a ristocetin A-bonded chiral stationary phase used in the reversed-phase and in the polar organic chromatographic modes is reported. The effects of different parameters such as mobile phase composition, temperature, and the structure of the analytes on the selectivity in both chromatographic modes are discussed. By variation of the parameters, the separation of the stereoisomers was optimized and, as a result, baseline resolution was achieved in most cases.

A new chiral derivatizing agent (CDA), (1S,2S)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propylisothiocyanate, (S,S)-DANI, was applied to the separation of the enantiomers of unusual amino acids containing two chiral centers. Different β-methyl-α-amino acids (β-MePhe, β-MeTyr and β-MeTrp) and β-amino acids with cycloalkane skeletons (2-aminocyclopentanecarboxylic acid and 2-aminocyclohexanecarboxylic acid) were derivatized and the thiourea derivatives produced were separated by reversed-phase high-performance liquid chromatography. The applicability of this new CDA in the separation of unusual amino acids is demonstrated. The four stereoisomers of the investigated amino acids (except β-MePhe) could be separated in one chromatographic run.

A short and general synthesis for the preparation of various conformationally constrained β-substituted tryptophans has been elaborated starting from indole, aldehydes and Meldrum's acid by using trimolecular condensation and Curtius rearrangement mediated functional group transformations followed by deprotections, as key-steps. The relative configurations of the two diastereomeric series have been determined indirectly by the measurement of 3J coupling constants in the corresponding tetrahydro-β-carbolines, and further supported by means of molecular modelizations.

In order to obtain constrained analogues of tryptophane, five-membered lactams and lactones bearing 4-indolyl and 3-carboxylic groups were prepared in a completely diastereoselective manner, resulting in a trans relationship. Furthermore, the use of chiral precursors in the synthesis yielded enantiomerically pure compounds with three contiguous chiral centres.