Karol Kacprzak

Chirality of aromatic bis-imides from their circular dichroism spectra

It is demonstrated that chirality of molecules composed of 1,2,4, 5-benzenetetracarboxydiimide (pyromellitic diimide) or 1,4,5, 8-naphthalenetetracarboxydiimide units is reflected by their exciton Cotton effects. The analysis is based on the calculated (ZINDO/S) excited states of the model diimide chromophores 1a and 2a. Rotation of the diimide chromophores around the C-N bond in diimides 3-5 is evaluated from the dynamic (1)H NMR data. A comparison of chiroptical properties of bis-diimides 3-5 with the CD spectra of bis-imides 6-8 is also presented. Copyright 2000 Wiley-Liss, Inc.

Identification of Lhcb1/Lhcb2/Lhcb3 heterotrimers of the main light-harvesting chlorophyll a/b-protein complex of Photosystem II (LHC II).

Using non-denaturing isoelectric focusing in polyacrylamide vertical slab gel, we have purified to homogeneity three trimeric subcomplexes of LHC II from Arabidopsis thylakoid membranes. The polypeptide composition of the subcomplexes were studied by immunoblotting. Our results indicate the existence in vivo of LHC II heterotrimers containing Lhcb1, Lhcb2 and Lhcb3 gene products.

Novel Pirkle-type quinine 3,5-dinitrophenylcarbamate chiral stationary phase implementing click chemistry

A new Pirkle-anion exchange hybrid-type chiral stationary phase (CSP-1) has been synthesized by immobilizing 10,11-didehydroquinine 3,5-dinitrophenylcarbamate onto 3-azidopropyl silica gel using click chemistry (1,3-dipolar Huisgen cycloaddition). This chiral selector and CSP contain a strong π-accepting 3,5-dinitrophenyl residue besides the π-basic quinoline group and an ionizable tertiary amino group. In concert with ion pairing it offers π-donor-π-acceptor interactions resulting in an enhancement of the selectivity toward specific π-donating analytes such as aryloxypropionic acids and profens. A representative set of these analytes has been investigated under various chromatographic conditions (polar-organic, reversed- and normal-phase) leading to base-line enantioseparations with selectivity (α) values up to 1.8. Control experiments with related quinine tert-butylcarbamate phase grafted onto the surface either by thioether (Chiralpak QN-AX) or 1,2,3-triazole linker revealed the impact of the additional aromatic moiety in the chiral selector motif.

Unexpected enantioseparation of mandelic acids and their derivatives on 1,2,3-triazolo-linked quinine tert-butyl carbamate anion exchange-type chiral stationary phase.

Replacement of the flexible thioether linker for the novel, rigid 1,2,3-triazole spacer group in the course of immobilization of quinine tert-butyl carbamate onto a silica surface led to a chiral stationary phase (CSP) with enhanced enantioselectivity for the resolution of mandelic acid and derivatives thereof. These new CSPs allowed efficient resolution of a wide set of mandelic acids with α-values between 1.08 and 1.68. The high loadability of these chiral ion exchange type CSPs allows preparative separation in the milligram range on an analytical column of 100×4 mm id in a single run as it was demonstrated for 4-trifluoromethylmandelic, 2-naphthylglycolic and 3,4-methylenedioxymandelic acids. The chiral recognition process has been studied using a library of 25 diverse racemic probes. A tentative model suggests that the rigid 1,2,3-triazole group takes part in the formation of an enantioselective-binding pocket of the entire and immobilized selector moiety of the CSP. The primary interaction site is given by the ionizable quinuclidine group of the Cinchona alkaloid supported by possible π-π stabilization effects within the selector-selectand complex.

Triazolo-linked cinchona alkaloid carbamate anion exchange-type chiral stationary phases: Synthesis by click chemistry and evaluation.

Immobilization strategy based on Huisgen 1,3-dipolar cycloaddition (click chemistry) of 10,11-didehydrocinchona tert-butylcarbamates to azido-grafted silica gels has been evaluated for preparation of novel chiral stationary phases (CSP 1-3). The resultant 1,2,3-triazole-linked CSPs were tested under various mobile phase conditions (polar organic and reversed phase mode) with a representative set of structurally diverse racemic acids including N-protected aminoacids, aromatic and aryloxycarboxylic acids as well as binaphthol phosphate. The chiral recognition performance of the C3-triazole-linked CSPs was found to mirror largely that of the known C3-thioether-linked CSP in terms of elution order, enantioselectivity and retention behavior. In an effort to assess the non-specific binding expressed as retention increment of these triazole-linked CSPs, the parent azidopropyl- and triazole-modified silica materials (thus not containing the chiral head ligand) were studied independently. Compared with the corresponding CSPs, the analyte retention on the azidopropyl control column was very low, and practically negligible on the corresponding triazole-modified reference column. Only minor losses in analyte retention behavior (<5%) were observed with triazole-linked CSPs after two month of continuous use with polar-organic and reversed-phase-type mobile phases, highlighting the excellent stability of the 1,2,3-triazole linker.

Antiproliferative Activity of Polyether Antibiotic – Cinchona Alkaloid Conjugates Obtained via Click Chemistry

A series of eight new conjugates of salinomycin or monensin and Cinchona alkaloids were obtained by the Cu(I)‐catalysed 1,3‐dipolar Huisgen cycloaddition (click chemistry) of respective N‐propargyl amides of salinomycin or monensin with four different Cinchona alkaloid derived azides. In vitro antiproliferative activity of these conjugates evaluated against three cancer cell lines (LoVo, LoVo/DX, HepG2) showed that four of the compounds exhibited high antiproliferative activity (IC50 below 3.00 μm) and appeared to be less toxic and more selective against normal cells than two standard anticancer drugs.

Simple and practical direct asymmetric aldol reaction of hydroxyacetone catalyzed by 9-amino Cinchona alkaloid tartrates

A novel organocatalytic procedure for the direct aldol reaction of unprotected acetol and activated aromatic aldehydes catalyzed by 9-amino-9-epi-Cinchona ditartrates is presented. The protocol presented avoids the use of problematic solvents and toxic reagents as well as chromatographic purification of the products – instead a simple extraction has been applied for the isolation of pure aldols from the reaction mixture. This catalytic system provides exclusively linear aldols with quantitative yields and good syn-diastereoselectivity and enantioselectvitiy up to 90% ee. Further upgrading of the enantiomeric excess of syn-aldols up to 99% ee is easily accomplished by a single and reliable crystallization. The use of cinchonine or quinine-derived catalysts gives access to both enantiomers of syn-aldols for which the absolute configuration has been determined by X-ray diffraction. The operationally convenient and scalable organocatalytic procedure using cheap and renewable chemicals – both acetol and the catalysts, offers a sustainable and green way for the synthesis of a number of α-keto-syn-diols.

Rapid and Convenient Microwave-Assisted Synthesis of Aromatic Imides and N-Hydroxymethylimides

Abstract Extremely simple high-yielding and rapid microwave-assisted synthesis of wide array of aromatic mono and diimides and mono- and bis-N-hydroxymethylimides is reported.

THE LIBRARY OF CINCHONA ALKALOIDS-1,2,3-TRIAZOLE DERIVATIVES: STRUCTURE AND FACILE ACCESS BY "CLICK CHEMISTRY"

New Cinchona alkaloids-1,2,3-triazole derivatives library was prepared readily and efficiently using Huisgen 1,3-dipolar cycloaddition of 9-azido substituted Cinchona alkaloids and various terminal and disubstituted alkynes (click chemistry). Spectroscopic, X-Ray, and molecular modelling data show that these derivatives maintain the conformation of the parent alkaloids.

In vitro antimicrobial activity of extracts and compounds isolated from Cladonia uncialis

Heptane (Hep), diethyl ether (Et2O), acetone (Me2CO) and methanolic (MeOH) extracts, as well as ( − )-usnic acid and squamatic acid, were obtained from thallus of Cladonia uncialis (Cladoniaceae). The antimicrobial activities of these extracts, ( − )-usnic acid and squamatic acid, were tested against reference strains: Staphylococcus aureus, Escherichia coli and Candida albicans. In addition, Me2CO extract was analysed against 10 strains of Methicillin-resistant S. aureus (MRSA) isolated from patients. All extracts exerted antibacterial activity against the reference strain S. aureus, comparably to chloramphenicol [minimum inhibitory concentration (MIC) = 5.0 μg/mL]. The Me2CO extract exhibited the strongest activity against S. aureus (MIC = 0.5 μg/mL), higher than ( − )-usnic acid, whereas squamatic acid proved inactive. The Me2CO extract showed potent antimicrobial activity against MRSA (MIC 2.5–7.5 μg/mL). Also no activity of C. uncialis extracts against E. coli and C. albicans was observed.