Cationic derivatives of polyprenols (trimethylpolyprenylammonium iodides – PTAI) with variable chain length between 6 and 15 isoprene units prepared from naturally occurring poly-cis-prenols were tested as DNA vaccine carriers in chickens and mice. This study aimed to investigate if PTAI could be used as an efficient carrier of a DNA vaccine. Several vaccine mixtures were prepared by combining different proportions of the vaccine plasmid (carrying cDNA encoding a vaccine antigen, hemagglutinin from H5N1 influenza virus) and various compositions of PTAI. The vaccines were delivered by intramuscular injection to either chickens or mice. The presence of specific antibodies in sera collected from the immunized animals was analyzed by enzyme-linked immunosorbent assay (ELISA) and hemagglutination inhibition (HI) test. The mixtures of PTAI with helper lipids, such as DOPE (1,2-dioleoyl-sn-glycero-3-phosphatidylethanolamine), DC-cholesterol [{3ß-[N-(N′,N′-dimethylaminoethane)-carbamoyl] cholesterol} hydrochloride] or DOPC (1,2-dioleoyl-sn-glycero-3-phosphatidylcholine) induced strong humoral response to the antigen encoded by the DNA vaccine plasmid. The animal immunization results confirmed that PTAI compositions, especially mixtures of PTAI with DOPE and DC-cholesterol, do work as effective carriers of DNA vaccines, comparable to the commercially available lipid transfection reagent.

The inexpensive and commercially available chlorosulfonyl isocyanate reacts readily with the variety of nucleophilic olefins to provide unstable [2+2]cycloadducts. The reaction proceeds via concerted mechanism rather than a stepwise process. The electron-donating substituent in the olefin component controls the regiochemistry of the reaction. The cycloaddition is stereospecific, leading from (Z)-olefin to the cis-adduct and from (E)-olefin to the trans-adduct. Increase of the reaction time or the presence of an acid contamination may result either in the epimerization at C(4) of the azetidin-2-one ring or in the rearrangement leading to the opening of the fourmembered ring. The N-deprotection of the [2+2]cycloadducts by reduction of the chlorosulfonyl group results in the formation of stable azetidin-2-ones, useful synthons in the synthesis of β-lactam antibiotics. The discussed reactions are sterically controlled and in many cases take place with a high asymmetric induction. Due to the observed exothermic nature of the cycloaddition, the conformation of the olefin in the transition state resembles, with a high probability, the low-energy ground-state conformation.

A formal synthesis of Thienamycin from ethyl (E)–crotonate and a cyclic five-membered nitrone derived from 2-deoxy-d-ribose is described. The synthesis involves 1,3-dipolar cycloaddition, cleavage of the N–O bond in the adduct, and intramolecular N-acylation to afford a bicyclic carbapenam skeleton. Subsequent transformations of the five-membered ring substituents provide the title compound.

This review provides a comprehensive compilation of available literature concerning the synthesis and applications of cyclic nitrones derived from sugars and hydroxyacids. The most important recent developments and concepts related to this topic are emphasized.

Intramolecular Kinugasa reactions on in situ generated carbohydrate-derived alkynylnitrones are described. The effects of the length of chains, their mutual configuration, influence of experimental conditions on product distribution and feasibility of the β-lactam ring construction were studied. Intramolecular reactions proceed with high stereoselectivity to provide in each case one product only. The cycloadducts from tartaric acid were converted into the corresponding non-racemic 4-acetoxy azetidinones in good yields.

An approach to β-lactams via a reaction between chiral copper acetylides and acyclic nitrones is reported. Electronic circular dichroism (ECD) in combination with NMR spectroscopy was used to determine the absolute configuration of all components of complex mixtures of azetidinones. Stereochemical preferences observed in the studied reactions are discussed and a model of a new reaction pathway supported by DFT conformational analysis is proposed. Subsequent transformations of the synthesized Kinugasa adducts followed by epimerization at the C-3 carbon atom led to trans-substituted azetidinones with improved stereoselectivity, mimicking a variety of important β-lactam structures. On the other hand, the oxidation of the furyl residue to the carboxylic group followed by oxidative decarboxylation with lead tetraacetate afforded the more thermodynamically stable trans-substituted 4-acetoxy azetidinone. The latter strategy is particularly attractive for the diastereomeric mixture in which isomers with the same configuration at the C-3 carbon atom dominate.