Synthesis, Crystal Structures, Lipophilic Properties and Antimicrobial Activity of 5-Pyridylmethylidene-3-rhodanine-carboxyalkyl Acids Derivatives.

The constant increase in the resistance of pathogenic bacteria to the commonly used drugs so far makes it necessary to search for new substances with antibacterial activity. Taking up this challenge, we obtained a series of rhodanine-3-carboxyalkyl acid derivatives containing 2- or 3- or 4-pyridinyl moiety at the C-5 position. These compounds were tested for their antibacterial and antifungal activities. They showed activity against Gram-positive bacteria while they were inactive against Gram-negative bacteria and yeast. In order to explain the relationship between the activity of the compounds and their structure, for selected derivatives crystal structures were determined using the X-ray diffraction method. Modeling of the isosurface of electron density was also performed. For all tested compounds their lipophilicity was determined by the RP-TLC method and by calculation methods. On the basis of the carried-out research, it was found that the derivatives with 1.5 N···S electrostatics interactions between the nitrogen atom in the pyridine moiety and the sulfur atom in the rhodanine system showed the highest biological activity.

Molecular Rearrangement of Pyrazino[2,3-c]quinolin-5(6H)-ones during Their Reaction with Isocyanic Acid.

New tetrahydropyrazino[2,3-c]quinolin-5(6H)-ones were prepared from 3-chloroquinoline-2,4(1H,3H)-diones and ethylene diamine. In their reaction with HNCO, an unprecedented molecular rearrangement produced new types of hydantoin derivatives. All prepared compounds were characterized on the basis of their 1H, 13C, and 15N NMR and ESI mass spectra and some were authenticated by X-ray analysis of single crystalline material. A proposed mechanism for rearrangement is discussed in this essay. The CDK and ABL inhibition activity as well as in vitro cytotoxicity of the prepared compounds was also tested.

Limitations of Trifluoromethylbenzoimidazolylbenzoic Acid as a Chiral Derivatizing Agent to Assign Absolute Configuration for ß-Chiral Aminoalcohols.

Axially chiral 2-(2-(trifluoromethyl)-1H-benzo[d]imidazole-1-yl)benzoic acid (TBBA) was used as a chiral derivatizing agent to evaluate the limits of absolute configuration assignment for ß-chiral aminoalcohols. Seven Boc-aminoalcohols and eight variously N-substituted (S)-phenylglycinols were prepared, and their TBBA esters were analyzed by NMR spectroscopy. Diverse substitution at the ß-position was employed to demonstrate the effect of structure on the general conformational model and reliability of the absolute configuration assignment. It was concluded that hydrogen bond formation and steric hindrance were the main factors affecting the correct assignment for Boc-aminoalcohols.

Lewis Superacidic Tellurenyl Cation-Induced Electrophilic Activation of an Inert Carborane.

The aryltellurenyl cation [2-(tBuNCH)C6 H4 Te]+ , a Lewis super acid, and the weakly coordinating carborane anion [CB11 H12 ]- , an extremely weak Brønsted acid (pKa =131.0 in MeCN), form an isolable ion pair complex [2-(tBuNCH)C6 H4 Te][CB11 H12 ], in which the Brønsted acidity (pKa 7.4 in MeCN) of the formally hydridic B-H bonds is dramatically increased by more than 120 orders of magnitude. The electrophilic activation of B-H bonds in the carborane moiety gives rise to a proton transfer from boron to nitrogen at slightly elevated temperatures, as rationalized by the isolation of a mixture of the zwitterionic isomers 12- and 7-[2-(tBuN{H}CH)C6 H4 Te(CB11 H11 )] in ratios ranging from 62 : 38 to 80 : 20.

Reaction of Tertiary 2-Chloroketones with Cyanide Ions: Application to 3-Chloroquinolinediones.

3-Chloroquinoline-2,4-diones react with cyanide ions in dimethyl formamide to give 3-cyanoquinoline-2,4-diones in small yields due to the strong hindrance of the substituent at the C-3 atom. Good yields can be achieved if the substituent at this position is the methyl group. In the methanol solution, the reaction proceeds by an addition mechanism to form 2-oxo-1a,2,3,7b-tetrahydrooxireno[2,3-c]quinoline-7b-carbonitriles, from which 4-hydroxy-3-methoxy-2-oxo-1,2,3,4-tetrahydroquinoline-4-carbonitriles are subsequently formed by opening of the epoxide ring with methanol. Some minor products of these reactions have also been isolated. The 1 H, 13 C and 15 N NMR spectra of the prepared compounds were measured, and all resonances were assigned using appropriate two-dimensional spectra.

Imidazo[1,2-c]pyrimidin-5(6H)-one inhibitors of CDK2: Synthesis, kinase inhibition and co-crystal structure.

Pharmacological inhibition of cyclin-dependent kinases has emerged as a possible treatment option for various cancer types. We recently identified substituted imidazo[1,2-c]pyrimidin-5(6H)-ones as inhibitors of cyclin-dependent kinase 2 (CDK2). Here, we report the synthesis of derivatives modified at positions 2, 3, 6 or 8 prepared using Suzuki-Miyaura cross-coupling, halogenation, Dimroth-type rearrangement and alkylation as the main synthetic methods. The compounds displayed micro- to submicromolar inhibition of CDK2/cyclin E activity. Binding of the most potent compound 3b to CDK2 was determined using isothermal titration calorimetry. The co-crystal structure of 3b in complex with fully active CDK2 was solved, revealing the binding mode of 3b in the ATP pocket and a hydrogen bonding interaction with hinge region residue Leu83. Evaluation against leukaemia cell lines revealed low cytotoxicity, which is in line with the high selectivity towards CDK2. This study demonstrates that substituted imidazo[1,2-c]pyrimidines can be exploited for future kinase inhibitor development.

New Mono- and Diesters with Imidazoquinolinone Ring- Synthesis, Structure Characterization, and Molecular Modeling.

The objective of the studies was to synthesize and characterize new mono- and diesters with an imidazoquinolin-2-one ring with the use of 2,3-dihydro-2-thioxo-1H-imidazo[4 ,5-c]-quinolin-4(5H)-ones and ethyl bromoacetate. The products were isolated at high yield and characterized by instrumental methods (IR, 1H-, 13C-, and 15N- NMR, MS-ESI, HR-MS, EA). In order to clarify the places of substitution and the structure of the derivatives obtained, molecular modeling of substrates and products was performed. Consideration of the possible tautomeric structures of the substrates confirmed the existence only the most stable keto form. Based on the free energy of monosubstituted ester derivatives, the most stable form were derivatives substituted at sulfur atom of enolic form the used imidazoquinolones. Enolic form referred only to nitrogen atom no 1. The modeling results were consistent with the experimental data. The HOMO electron densities at selected atoms of each substrate has shown that the most reactive atom is sulfur atom. It explained the formation of monoderivatives substituted at sulfur atom. The diester derivatives of the used imidazoquinolones had second substituent at nitrogen atom no. 3. The new diesters can be used as raw material for synthesis of thermally stable polymers, and they can also have biological activity.

Benzothiazolyl Ureas are Low Micromolar and Uncompetitive Inhibitors of 17ß-HSD10 with Implications to Alzheimer's Disease Treatment.

Human 17ß-hydroxysteroid dehydrogenase type 10 is a multifunctional protein involved in many enzymatic and structural processes within mitochondria. This enzyme was suggested to be involved in several neurological diseases, e.g., mental retardation, Parkinson's disease, or Alzheimer's disease, in which it was shown to interact with the amyloid-beta peptide. We prepared approximately 60 new compounds based on a benzothiazolyl scaffold and evaluated their inhibitory ability and mechanism of action. The most potent inhibitors contained 3-chloro and 4-hydroxy substitution on the phenyl ring moiety, a small substituent at position 6 on the benzothiazole moiety, and the two moieties were connected via a urea linker (4at, 4bb, and 4bg). These compounds exhibited IC50 values of 1-2 µM and showed an uncompetitive mechanism of action with respect to the substrate, acetoacetyl-CoA. These uncompetitive benzothiazolyl inhibitors of 17ß-hydroxysteroid dehydrogenase type 10 are promising compounds for potential drugs for neurodegenerative diseases that warrant further research and development.

Axially Chiral Trifluoromethylbenzimidazolylbenzoic Acid: A Chiral Derivatizing Agent for α-Chiral Primary Amines and Secondary Alcohols To Determine the Absolute Configuration.

Racemic 2-(2-trifluoromethyl)-1H-benzo[d]imidazol-1-yl)benzoic acid (TBBA) was synthesized in three steps from 1-fluoro-2-nitrobenzene. Target (P)- and (M)-TBBA atropisomers were stable with a racemization barrier above 30 kcal/mol. As a chiral derivatizing agent, TBBA showed much higher differences in chemical shifts (ΔδPM) than the conventional Mosher's acid.

Imidazo[1,2-c]pyrimidin-5(6H)-one as a novel core of cyclin-dependent kinase 2 inhibitors: Synthesis, activity measurement, docking, and quantum mechanical scoring.

We report on the synthesis, activity testing, docking, and quantum mechanical scoring of novel imidazo[1,2-c]pyrimidin-5(6H)-one scaffold for cyclin-dependent kinase 2 (CDK2) inhibition. A series of 26 compounds substituted with aromatic moieties at position 8 has been tested in in vitro enzyme assays and shown to inhibit CDK2. 2D structure-activity relationships have ascertained that small substituents at position 8 (up to the size of naphtyl or methoxyphenyl) generally lead to single-digit micromolar IC50 values, whereas bigger substituents (substituted biphenyls) decreased the compounds' activities. The binding modes of the compounds obtained using Glide docking have exhibited up to 2 hinge-region hydrogen bonds to CDK2 and differed in the orientation of the inhibitor core and the placement of the 8-substituents. Semiempirical quantum mechanics-based scoring identified probable favourable binding modes, which will serve for future structure-based design and synthetic optimization of substituents of the heterocyclic core. In summary, we have identified a novel core for CDK2 inhibition and will explore it further to increase the potencies of the compounds and also monitor selectivities against other protein kinases.

Preparation and characterization of novel double-decker rare-earth phthalocyanines substituted with 5-bromo-2-thienyl groups.

BACKGROUND: A series of rare-earth bisphthalocyanines of praseodymium, samarium and gadolinium bearing 5-bromo-2-thienyl substituents were prepared for the first time. RESULTS: Three bis[octakis(5-bromo-2-thienyl)] rare-earth metal(III) bisphthalocyanine complexes (Pr, Sm, Gd) were synthesized for the first time. The new compounds were characterized by UV-vis, NIR, FT-IR, mass spectroscopy and thermogravimetry as well as elementary analysis and electrochemistry. Production of singlet oxygen was also estimated using 9,10-dimethylanthracene method. CONCLUSIONS: The bromine substituent causes significant changes in molecule paramagnetism, singlet oxygen production, HOMO position and spectral characteristics. The compounds in solutions exist in two forms (neutral and/or reduced) depending on the solvent and rare-earth metal. Moreover, the compounds exhibit much increased stability under acid conditions compared with non-brominated derivatives. Graphical abstract Prepared compounds for the study of their chemical and other properties.

Design, synthesis and antitubercular potency of 4-hydroxyquinolin-2(1H)-ones.

In this study, a 50-membered library of substituted 4-hydroxyquinolin-2(1H)-ones and two closely related analogues was designed, scored in-silico for drug likeness and subsequently synthesized. Thirteen derivatives, all sharing a common 3-phenyl substituent showed minimal inhibitory concentrations against Mycobacterium tuberculosis H37Ra below 10 µM and against Mycobacterium bovis AN5A below 15 µM but were inactive against faster growing mycobacterial species. None of these selected derivatives showed significant acute toxicity against MRC-5 cells or early signs of genotoxicity in the Vitotox™ assay at the active concentration range. The structure activity study relation provided some insight in the further favourable substitution pattern at the 4-hydroxyquinolin-2(1H)-one scaffold and finally 6-fluoro-4-hydroxy-3-phenylquinolin-2(1H)-one (38) was selected as the most promising member of the library with a MIC of 3.2 µM and a CC50 against MRC-5 of 67.4 µM.

Hydrosilylation of RN=CH Imino-Substituted Pyridines without a Catalyst.

Treatment of the neutral pyridine-based ligands L1 -L3 , bearing either one or two RN=CH imine moieties {where L1 and L2 are N,N-chelating ligands 2-(RN=CH)C5 H4 N (R=Ph (L1 ) or R=2,4,6-Ph3 C6 H2 (L2 )) and L3 is the N,N,N-chelating ligand 2,6-(RN=CH)2 C5 H3 N (R=2,6-iPr2 C6 H3 )}, with HSiCl3 yielded N→Si-coordinated silicon(IV) amides 2-{Cl3 SiN(R)CH2 }C5 H4 N (1, R=Ph; 2, R=2,4,6-Ph3 C6 H2 ) and 2-{Cl3 SiN(R)CH2 }-6-(RN=CH)C5 H4 N (3, R=2,6-iPr2 C6 H3 ). The organosilicon amides 1-3 are the products of spontaneous hydrosilylation of the RN=CH imine moiety induced by N→Si coordination of the proposed N,N-chelated chlorosilanes L1 →SiHCl3 (1 a), L2 →SiHCl3 (2 a), and L3 →SiHCl3 (3 a). Furthermore, the reaction of L3 with an excess of HSiCl3 provided the intramolecularly coordinated chlorosilicon diamide cyclo-{(C5 H3 N)-1,3-(CH2 NR)2 }SiCl2 (4) (R=2,6-iPr2 C6 H3 ) as the product of spontaneous reduction of both RN=CH imine moieties. The compounds have been characterized by NMR spectroscopy (1-4) and single-crystal X-ray diffraction analysis (1, 3, and 4). The mechanism of the hydrosilylation of the second RN=CH imine moiety in 3 by an excess of SiHCl3 has also been studied. The experimental work is supplemented by DFT calculations.

Homolytic, Heterolytic, Mesolytic - As You Like It: Steering the Cleavage of a HC(sp3 )-C(sp3 )H Bond in Bis(1H-2,1-benzazaborole) Derivatives.

A set of (3,3')-bis(1-Ph-2-R-1H-2,1-benzazaborole) compounds, in which R=tBu (Bab-tBu)2 , R=Dipp (Bab-Dipp)2 or R=tBu and Dipp (Bab-Dipp)(Bab-tBu), was synthesized and fully characterized using 1 H, 11 B, 13 C, and 15 N NMR spectroscopy as well as single-crystal X-ray diffraction analysis. The central HC(sp3 )-C(sp3 )H bond with restricted rotation at the junction of both 1H-2,1-benzazaborole rings displayed an intriguing reactivity. It was demonstrated that this bond is easily mesolytically cleaved using alkali metals to form the respective aromatic 1Ph-2R-1H-2,1-benzazaborolyl anions M+ (THF)n (Bab-tBu)- (M=Li, Na, K) and K+ (THF)n (Bab-Dipp)- . Furthermore, the central HC(sp3 )-C(sp3 )H bond of bis(1H-2,1-benzazaborole)s is also homolytically cleaved either by heating or photochemical means, giving corresponding 1Ph-2R-1H-2,1-benzazaborolyl radicals (Bab-tBu). and (Bab-Dipp). , which rapidly self-terminate. Nevertheless, their formation was unambiguously established by NMR analysis of the reaction mixtures containing products of the self-termination of the radicals after heating or irradiation. (Bab-Dipp). radical was also characterized using EPR spectroscopy. Importantly, it turned out that the essentially non-polarized HC(sp3 )-C(sp3 )H bond in (Bab-tBu)2 is also cleaved heterolytically with 2 equiv of MeLi, giving the mixture of Li+ (SOL)n (Bab-tBu)- (SOL=THF or Et2 O) and lithium methyl-substituted borate complex Li+ (SOL)n (Bab-tBu-Me)- in a diastereoselective fashion.

Germylenes and stannylenes stabilized within N2PE rings (E = Ge or Sn): combined experimental and theoretical study.

The deprotonation of aminophosphanes PhP(NHR)2 (R = t-Bu or Dip; Dip = 2,6-i-Pr2C6H3) and t-BuP(NHDip)2 using n-BuLi gave, depending on the stoichiometry, both the dilithium compounds {[PhP(Nt-Bu)2]Li2}2 (), [PhP(Nt-Bu)(NDip)]Li2·(Et2O) (), [t-BuP(NDip)2]Li2·(Et2O)2 () and [t-BuP(NDip)2]Li2·(tmeda)2 (), and the monolithium compounds [PhP(NHt-Bu)(NR)]Li·(tmeda) (R = t-Bu , Dip ) and [t-BuP(NHDip)(NDip)]Li·(tmeda) (). Treatment of , and with GeCl2·dioxane or SnCl2 in a 1 : 1 stoichiometric ratio gave the corresponding tetrylenes [PhP(Nt-Bu)2]E (E = Ge , Sn ), [PhP(Nt-Bu)(NDip)]Ge () and [t-BuP(NDip)2]E (E = Ge , Sn ). The heteroleptic germylene [Ph(H)P(Nt-Bu)2]GeCl () was obtained by the reaction of the monolithium compound [PhP(NHt-Bu)(Nt-Bu)]Li·(tmeda) () with GeCl2·dioxane in a 1 : 1 stoichiometric ratio, as a result of a spontaneous NH → PH tautomeric shift in the ligand backbone. In contrast, an analogous reaction with SnCl2 produced only stannylene along with the PhP(NHt-Bu)2 starting material, suggesting scrambling of the ligands rather than a NH → PH tautomeric shift. Finally, heating in solution led to P-C bond cleavage and formation of the bis(imino)phosphide [DipNPNDip]Li·(tmeda) (). The reaction of with GeCl2·dioxane, SnCl2 or PbCl2 in a 2 : 1 stoichiometric ratio yielded the unprecedented tetrylenes [DipNPNDip]2E (E = Ge , Sn and Pb ), in which the tetrylene center is incorporated within two N2PE rings. Treatment of the monolithium compound with n-BuLi and K (or KC8) gave [t-BuNPNt-Bu]Li·(tmeda) () and{[t-BuNPNt-Bu]K(tmeda)}2 (), respectively. In contrast to the reaction with , similar reactions of with GeCl2·dioxane and SnCl2 resulted in the known compounds cis-[P(µ-Nt-Bu)2P(t-BuN)2]E (E = Ge, Sn); evidently the t-Bu groups do not provide sufficient steric shielding to protect the bis(imino)phosphide backbone as in the case of . The bonding situation in a set of selected compounds (, ) has been subjected to a theoretical survey with particular emphasis on the nature of the bonding between the ligand and the central metal and the bonding within the NPN core of the ligand, showing significant differences among the studied complexes.

Analytical Characterization of Erythritol Tetranitrate, an Improvised Explosive.

Erythritol tetranitrate (ETN), an ester of nitric acid and erythritol, is a solid crystalline explosive with high explosive performance. Although it has never been used in any industrial or military application, it has become one of the most prepared and misused improvise explosives. In this study, several analytical techniques were explored to facilitate analysis in forensic laboratories. FTIR and Raman spectrometry measurements expand existing data and bring more detailed assignment of bands through the parallel study of erythritol [(15) N4 ] tetranitrate. In the case of powder diffraction, recently published data were verified, and (1) H, (13) C, and (15) N NMR spectra are discussed in detail. The technique of electrospray ionization tandem mass spectrometry was successfully used for the analysis of ETN. Described methods allow fast, versatile, and reliable detection or analysis of samples containing erythritol tetranitrate in forensic laboratories.

Non-Catalyzed Click Reactions of ADIBO Derivatives with 5-Methyluridine Azides and Conformational Study of the Resulting Triazoles.

Copper-free click reactions between a dibenzoazocine derivative and azides derived from 5-methyluridine were investigated. The non-catalyzed reaction yielded both regioisomers in an approximately equivalent ratio. The NMR spectra of each regioisomer revealed conformational isomery. The ratio of isomers was dependent on the type of regioisomer and the type of solvent. The synthesis of various analogs, a detailed NMR study and computational modeling provided evidence that the isomery was dependent on the interaction of the azocine and pyrimidine parts.

From Stiba- and Bismaheteroboroxines to N,C,N-Chelated Diorganoantimony(III) and Bismuth(III) Cations-An Unexpected Case of Aryl Group Migration.

An unprecedented transfer of an aryl group from boron to Sb and Bi is observed in the reaction of heteroboroxines of general formula ArM[(OBR)2O] [where M = Sb, Bi; Ar = C6H3-2,6-(CH2NMe2)2; R = Ph, 4-CF3C6H4, 4-BrC6H4] with corresponding boronic acid RB(OH)2. Using this procedure, ion pairs [ArMR](+)[R4B5O6](-) were obtained [where M = Sb and R = Ph (4), 4-CF3C6H4 (5), 4-BrC6H4 (6); where M = Bi and R = Ph (7), 4-CF3C6H4 (8), 4-BrC6H4 (9)]. All compounds were characterized using elemental analysis, electrospray ionization mass spectrometry, and multinuclear NMR spectroscopy, and molecular structures of 4 and 7 were determined by single-crystal X-ray diffraction analysis. The central metal atoms in 4-9 were arylated by respective boronic acids, which represents, to the best of our knowledge, unprecedented reaction path in the chemistry of heavier group 15 elements. Investigation of the mechanism of this transformation indicated that Lewis pairs consisting of monomeric oxides ArMO and boroxine rings are probably key intermediates. In this regard, molecular structures of ArSbO[(4-CF3C6H4)3B3O3]·(4-CF3C6H4)B(OH)2 (10) and {ArSbO[(3,5-(CF3)2C6H3)3B3O3]} (13) were established by single-crystal X-ray diffraction analysis, and compound 13 was also fully characterized in solution by multinuclear NMR spectroscopy. The bonding in 13 was analyzed in detail by using density functional theory and natural bond order calculations and compared with known adduct ArSbOB(C6F5)3 (14) and hypothetical ArSbO monomer.

Reactivity of bis(organoamino)phosphanes with magnesium(II) compounds.

The reactivity of three phosphanes (PhP(NHR)2 [R = t-Bu (1), Ph (2)] and PhP(NEt2)(NHDip) (3) (where Dip = 2,6-i-Pr2C6H3)) with n-Bu2Mg and MeMgBr is presented. In the case of 1, the reaction with n-Bu2Mg gave [PhP(NHt-Bu)(Nt-Bu)]Mg(n-Bu) (4) or [PhP(NHt-Bu)(Nt-Bu)]2Mg (5) depending on the stoichiometry. The treatment of 1 with MeMgBr led to the phosphinate [Ph(H)P(Nt-Bu)2]2Mg (7) as a result of both the NH→PH tautomeric transformation and elimination of MgBr2 from the non-isolable intermediate [PhP(NHt-Bu)(Nt-Bu)]MgBr(THF) (6). Phosphane 2 reacted with n-Bu2Mg in a 1:1 molar ratio resulting in the formation of {[PhP(NPh)2]2Mg(THF)2}2 (8), but the analogous reaction in a 2:1 molar ratio yielded phosphinate [Ph(H)P(NPh)2]2Mg(THF) (9). The heteroleptic compound [Ph(H)P(NPh)2]MgBr(THF)2 (10) was obtained by the reaction of 2 with MeMgBr. Finally, the reaction of 3 with n-Bu2Mg and MeMgBr produced compounds [PhP(NEt2)(NDip)]2Mg (11) and {[PhP(NEt2)(NDip)2]Mg(µ-Br)(THF)}2 (12), respectively. All products were characterized using (1)H, (13)C{(1)H} and (31)P NMR spectroscopy and, except for compounds 4 and 6, their molecular structures were determined using single-crystal X-ray diffraction analysis. In addition, a theoretical study on plausible isomers of 10 was performed to provide additional evidence for the presence of a syn- and anti-isomer in dynamic equilibrium in a solution of 10.

From C,N- and N,N-chelated chloroboranes to substituted 1H-2,1-benzazaboroles and 1H-pyrrolo[1,2-c][1,3,2]diazaborolidines: a straightforward route to five-membered rings containing the B-N or N-B-N moiety.

A set of 1H-2,1-benzazaboroles as B-N analogues of 1H-indene and a set of 1H-pyrrolo[1,2-c][1,3,2]diazaborolidines as B-N analogues of 1H-pyrrolizine were prepared via nucleophilic addition of selected alkyl(aryl)lithiums (MeLi, tBuLi or PhLi) to, via N→B intramolecular interactions, the activated imino C[double bond, length as m-dash]N functionality in the structure of C,N- or N,N-chelated chloroboranes. All compounds were characterized by elemental analysis and (1)H, (11)B, (13)C and (15)N NMR spectroscopy, and molecular structures of isolated compounds were on several occasions established by means of single-crystal X-ray diffraction analysis. The presence of three adjacently bonded substituents and their systematic alternation on five-membered C3BN (1H-2,1-benzazaboroles) or C2BN2 (1H-pyrrolo[1,2-c][1,3,2]diazaborolidines) rings allowed us to follow both the influence of the steric repulsion and limitations for the formation of respective annulated heterocyclic systems.