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A series of novel hydantoin-based dispiroindolinones as potential small-molecule inhibitors of p53–MDM2 protein–protein interaction were synthesized by two methods, using 2-arylidenehydantoins as starting materials. Some compounds demonstrate moderate cytotoxicity against cancer cell lines with IC50 in micromolar concentration range, which is comparable to nutlin-3. Two of the synthesized dispiroindolinones show p53-related activity in p53 reporter activation test.

The IR spectra in the hydroxyl group stretching vibration region of the simplest hydroxyalkylpyrrolizidines have been examined. The spectra were taken in the form of pure liquids, dilute solutions in carbon tetrachloride, and for individual bases in the gas phase. It was shown that in dilute solutions ΔνOH depends on the geometric parameters of the intramolecular hydrogen bond (IMHB). The energy of the IMHB of 3-(2-hydroxyethyl)pyrrolizidine was measured in dilute solution and in the gas phase.

The cis-trans conversion in pyrrolizidines and the deciding effect of steric factors on their conformational equilibrium are discussed. Work on the synthesis and characteristics of sterically strained pyrrolizidines is analyzed and discussed. It is shown that such compounds (predominantly trans-fused) have a series of features in their properties that greatly distinguish them from unstrained pyrrolizidines. The first results from study of the thermodynamics of cis-trans conversion of the pyrrolizidine bicycle are summarized.

Data have been summarized of several studies on the separation of isomeric pyrrolizidine alcohols by GLC using liquid polar stationary phases. It was shown that the order of emergence of isomers from the chromatographic column is determined to a significant extent by competition of intermolecular hydrogen bonds formed in the sorbate-sorbent systems and intramolecular hydrogen bonds in the molecules of the same pyrrolizidine alcohols. The preference for one or other type of hydrogen bond depends on the stereochemistry of the pyrrolizidine alcohols. Analysis of the geometric conditions for the formation of intramolecular hydrogen bonds in the investigated compounds in conjunction with chromatographic resolution data enables their configurations to be assigned. The anomalously short retention times of highly strained 5-hydroxyalkyl-3-methylpyrrolizidines are explained by the existence in them of a bicyclic conformation predominantly with a trans linkage and with f avora ble geometric conditions for forming intramolecular hydrogen bonds in them.

A simple method for the synthesis of 5,5-dimethyl-4-cyanomethylene-2-cyanomethyl-2-[1-methyl-1-(carbamoyloxy)ethyl]-1,3-dithiolanes was developed on the basis of the reaction of 5,5-dimethyl-4-cyanomethylene-1,3-oxathiolan-2-one with amines (primary and secondary) and ammonia.

Known methods for the synthesis of 1,2-dihydropyrrolizines are presented in a systematized form. Literature data on the chemical properties of 1,2-dihydropyrrolizines are summarized and correlated; and synthetic, physiologically active substances belonging to this group of compounds are examined critically.

13C NMR spectra were obtained for pyrrolizidinium salts and their homologs and their signals were assigned. With the exception of highly strained cis-3,8-H-cis-5,8-H-3,5-dimethylpyrrolizidine (VI), all the bases studied upon their direct mixing with CF3CO2H form salts only with cis-fused rings in the cation. Mixtures of salts with cis- and trans-fused pyrrolizidinium fragments are formed upon the reaction of cis-3,8-H-methy1- (III) and cis-3,8-H-cis-5,8-H-3,5-dimethylpyrrolizidine (VI) under conditions close to those for kinetically-controlled amine protonation. The13C NHR spectra of the isomeric pyrrolizidinium salts obtained as a result of the absorption of base VI by sulfuric acid were used to evaluate the conformational equilibrium in the starting compound VI. The13C NMR chemical shifts of unsubstituted trans-fused pyrrolizidinium salts were predicted.