Zofia Urbanczyk-Lipkowska

Advances in the chemistry of dendrimers

Dendrimers, which are highly branched, multivalent and monodisperse polymers, have received continuous interest in recent years because of the global demand for new nanomolecules that are useful in advanced technology and medicine. While dendrimers are advantageous for many highly specialised applications, the high polyvalency of higher-generation dendrimers requires, however, well-controlled, target-tailored regioselective chemical engineering. The structural evolution of dendrimers – from simple, monofunctional molecules to the more complex, multifunctional compounds – is inextricably associated with a continuous improvement in traditional synthetic strategies, as well as the development of new synthetic tools. The purpose of this review is to provide insight into currently available synthetic methods that yield dendrimers with various morphologies, placing emphasis on the evaluation of their advantages and limitations. In particular, we will review current efforts that focus on simplifying and optimising the existing methods and the development of new strategies that permit control over the targeted introduction of various functionalities in one or more selected areas of the molecule.

New optically pure sugar hydroperoxides. Synhtesis and use for enantioselective oxygen transfer

Abstract 2-Deoxy-2-C-methylene methyl glycosides undergo oxidation with hydrogen peroxide in the presence of molybdenum trioxide as catalyst to afford the corresponding anomeric hydroperoxides. These hydroperoxides were used as chiral oxidants of allylic alcohols and prochiral sulfides to offer moderate enantioselectivities which were, however, higher than those reported before oxidation with optically active peroxyacids.

Syntheses of pyrrolizidines and indolizidines from α,β-unsaturated sugar δ-lactones via Dieckmann condensation

Abstract Both N-methoxycarbonylmethyl- and N-methoxycarbonylethyl-derivatives of dihydroxy-( d )-homoproline were subjected to the intramolecular ester condensation to yield ketoesters of pyrrolizidine and indolizidine series, respectively. The former ketoester was transformed into derivative related to australine, while the latter were transformed into the natural lentiginosine as well as its 2-epi-, and 7-hydroxy-2-epi-derivatives.

Novel dendrimeric lipopeptides with antifungal activity.

A series of new cationic lipopeptides containing branched, amphiphilic polar head derived from (Lys)Lys(Lys) dendron and C(8) or C(12) chain at C-end were designed, synthesized and characterized. Antimicrobial in vitro activity expressed as minimal inhibitory concentration (MIC) was evaluated against Gram-positive and Gram-negative bacteria and yeasts from the Candida genus. A significant enhancement of antimicrobial potency along with increased selectivity against Candida reference strains was detected for derivatives with the C(12) residue. Several compounds were characterized by a low hemotoxicity. The antifungal activity of branched lipopeptides is multimodal and concentration dependent. Several compounds, studied in detail, induced potassium leakage from fungal cells, caused morphological alterations of fungal cells and inhibited activity of candidal β(1,3)-glucan synthase.

Cooperative effect of multiple hydrogen bonding involving the nitro group: solid state dimeric self-assembly of o-, m- and p-hydroxyphenyl-2,4-dinitrophenylhydrazones

Solid state studies of o-, m-, and p-hydroxyphenyl-2,4-dinitrophenylhydrazones: 1, 2, 3 and 4 (3·0.5 MeCN) revealed dimeric self-assembly of molecules. A pattern of two NH⋯O2N and up to six CH⋯O2N intermolecular hydrogen bonds creates cohesive forces between two molecules of the dimer. Push–pull effects of numerous weak interactions generate non-bonding contacts between negatively charged O atoms of the o-NO2 groups in the range 2.683(2)–2.894(3) A, far below the sum of van der Waals radii. Both the presence of OH groups and MeCN molecules in the crystals does not interfere much with dimer formation. Low temperature X-ray data collected for compound 1 provided evidence that due to the involvement of the o-NO2 group oxygen in a new type of intramolecular, resonance-assisted hydrogen-bonded system (RAHB), the phenyl ring has a 2,5-diene geometry. The packing patterns observed in crystals of compounds 1–4 are explained as a result of competition between in-plane hydrogen bonding and inter-planar interactions dominated by π–π stacking and dipole–dipole overlap. FT-IR data confirm aggregation in solution. Another examples of short contacts between nitro group oxygens found in the Cambridge Crystallographic Database are discussed.

Synthesis of pyrrolizidine alkaloids via 1,3-dipolar cycloaddition involving cyclic nitrones and unsaturated lactones

The 1,3-dipolar cycloaddition of cyclic nitrone derived from tartaric acid and (S)-5-hydroxymethyl-2(5H)-furanone leads to a single adduct which was transformed into 2,6-dihydroxyhastanecine via reaction sequence involving reduction of the lactone moiety, glycolic cleavage of the terminal diol, and the N-O hydrogenolysis followed by the intramolecular alkylation of the nitrogen atom.

1,3-Dipolar cycloaddition of a nitrone derived from (S)-malic acid to α,β-unsaturated δ-lactones

Abstract 1,3-Dipolar cycloaddition of nitrone 7 to α,β-unsaturated δ-lactones: non-chiral 2, racemic mixture 3/3ent, d -glycero 3 and d -threo 15 proceeds with high stereoselectivity in the case of 2 and 15, and with a significant kinetic resolution in the case of the racemate 3/3ent. The endo approach of reactants was not observed. CD-spectroscopy proved an attractive tool for determination of the absolute configuration of cycloadducts.

1,3-dipolar cycloaddition of nitrones to sugar enlactones

It was found that 1,3-dipolar cycloaddition of nitrones derived from formaldehyde and acetaldehyde to sugar enlactones proceeds regio- and stereospecifically to afford anti - endo adducts.

Design of antimicrobially active small amphiphilic peptide dendrimers.

Novel polyfunctional small amphiphilic peptide dendrimers characterized by incorporation of a new core compounds – tris-amino acids or tetrakis-amino alcohols that originated from a series of basic amino acids – were efficiently synthesized. These new core elements yielded molecules with multiple branching and (+5)/(+6) charge at the 1-st dendrimer generation. Dendrimers exhibited significant antimicrobial potency against Gram(+) and Gram(-) strains involving also multiresistant reference strains (S. aureus ATCC 43300 and E. coli ATCC BAA-198). In addition, high activity against fungi from the Candida genus was detected. More charged and more hydrophobic peptide dendrimers expressed hemolytic properties.

Double Asymmetric Induction in 1,3‐Dipolar Cycloaddition of Nitrones to 2,3‐Unsaturated Sugar 1,5‐Lactones

1,3‐Dipolar cycloaddition of nitrones 1–3 to the α,β‐unsaturated δ‐lactones, non‐chiral 4, d‐glycero 5, dl‐glycero 5/5ent, d‐erythro 6, and d‐threo 7, provides an interesting example of a double asymmetric induction. In all cases, only the exo approach of reactants was observed. The high preference of anti addition of the nitrones to the terminal acetoxymethyl group in the lactones 5–7 is consistent with previous observations, and can be explained in terms of the axial approach of the nitrone oxygen atom. The 3‐t‐butoxy group of the nitrone plays a similar role. In the case of mismatched pairs, the location of the 4‐acetoxy substituent in the lactone and that of the 4‐t‐butoxy one in the nitrone become decisive for the outcome of the addition. CD‐spectroscopy proved to be an attractive tool to determine the absolute configuration of the cycloadducts. †This paper is dedicated to Professor Gérard Descotes on the occasion of his 70th birthday.