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A convenient practical home-made continuous flow-photochemistry setup was evaluated with the aim to enable a more efficient protocol for the synthesis of functionalized benzobicyclo[3.2.l]octadiene skeleton by intramolecular [2+2]-photocycloaddition reaction. Numerous compounds with the bicyclo[3.2.l]-skeleton are proven as potent inhibitors of dopamine and serotonin transporters and also play a crucial role in treatment of central nervous system and Alzheimer's disorders. The yields, reaction times and conversions gained from the flow setup were compared to those obtained from the conventional photoreactor. In comparison to the batch reaction, the flow reaction showed better results, both in increasing the isolated yield and productivity and in lowering the reaction time. This first application of the flow-photochemistry on β -heteroaryl- o -divinylbenzenes and o -vinylphenyl substituted butadienes proved to be more efficient and less sensitive to oxygen enabling us to scale-up the intramolecular cycloaddition without scaling-up the equipment. Additionally, for all the obtained, potentially bioactive, derivatives promising calculated physico-chemical and absorption, distribution, metabolism, and elimination (ADME) properties were also given. [ABSTRACT FROM AUTHOR]

New hetero-stilbene derivatives, namely cis / trans -2/3/4-(2-vinylstyryl)pyridines, have been synthesized by Wittig reaction from the diphosphonium salt of α,α ′- o -xylenedibromide, formaldehyde and 2/3/4-pyridinecarbaldehydes. The 2/3/4-(2-vinylstyryl)pyridines afforded, by photochemical intramolecular cycloaddition and cyclization reactions, diverse new polycyclic products with the pyridine ring integrated into the polycyclic skeletons. All of the new benzobicyclo[3.2.1]octadiene, benzobicyclo[2.1.1]hexene and vinyl-benzoquinoline products were identified and characterized by spectroscopic methods. Isomerized dihydro-intermediates (DHQs), that formed as a result of [1,n- H ] shifts were also isolated, identified and characterized. DHQ intermediate isomers were never isolated in these conditions before. [ABSTRACT FROM AUTHOR]

The Diels–Alder reaction was exploited for the preparation of novel long-wavelength chlorin photodynamic therapy photosensitizers. The styryl group and furan carboxamide substituents were used as diene components in [4+2] cycloaddition functionalizations. [ABSTRACT FROM AUTHOR]

New polycyclic compounds are synthesized by photocycloaddition reactions of methoxy, methyl or phenyl substituted butadiene derivatives 11-14. Mono- and dimethoxy butadiene derivatives 11 and 12 undergo intramolecular [2+2] photocycloaddition giving benzobicyclo[3.2.1]octadiene structures (endo-15, endo,trans-17) as main products. As minor photoproducts tricyclic compounds endo-16 and endo,do,trans-18 are isolated, respectively, formed by [4+2] photoinduced cycloaddition of the starting molecules. The reaction of compounds 13 and 14 is more selective and only benzobicyclo[3.2.1]octadienes en-do,endo-19 and endo,endo-19 are formed, respectively. New bicyclo[3.2.1]octadienes with isolated double bond can be suitable substrates for further efficient photocatalytic oxygenations in course of new functionalized polycycles, potentially new biologically active compounds. [ABSTRACT FROM AUTHOR]

Abstract: Thermal electrocyclization reactions of benzooctatetraenes and benzodecapentaenes substituted with R=H, Cl, and methyl were studied experimentally and computationally. Methyl and unsubstituted benzooctatetraenes and benzodecapentaenes give the [4.2.0]bicyclooctadiene products by 8π,6π-electrocyclization. Chlorine substitution led to thermal rearrangement of the initially formed 8π,6π-electrocyclization intermediates to give unprecedented products. [Copyright &y& Elsevier]

Intramolecular photochemical reactions of thiophene analogues of o-distyrylbenzene, 2,2'-(o-phenylenedivinylene) dithiophenes (1a,b), 3,3'-(o-phenylenedivinylene)dithiophene (2a) and 3,3'-(o-phenylenedivinylene) dibenzothiophene (2b), were studied in acidic media at low concentrations. A 1,6- and 1,5-ring closure of hexatriene system leading to dihydronaphthalene or indene derivatives, respectively, was observed. [ABSTRACT FROM AUTHOR]

A series of novel stilbene-sydnone derivatives were synthesized by the following sequence of reactions: starting from methyl anthranilate via glycine- and nitrosoglycine derivatives the corresponding 3-(o-carbomethoxyphenyl)-4-H/Me/Ph-sydnones were prepared and transformed to 3-(o-formylphenyl)-4-H/Me/Ph-sydnones, starting materials for Wittig reaction with various phosphonium salts to stilbenylsydnone derivatives. Final products were evaluated for their cytotoxic properties on five cancer cell lines, whereby the cis-4-methyl-3-[2-[2-(4-methylphenyl)ethenyl]phenyl]sydnone 5 and cis-4-phenyl-3-[2-[2-(4-chlorophenyl)ethenyl]- phenyl]sydnone 10 showed the most pronounced activity. [ABSTRACT FROM AUTHOR]

Abstract: Low density lipoprotein (LDL) particles exhibit extremely complex three-dimensional structural organization which is still not understood at the molecular level. The aim of this study was to provide the experimental evidence of a direct non-covalent interaction of the protein part with the lipid matrix. The approach was based on the combination of 1H NMR (600MHz) spectroscopy with thiol-specific spin labeling of the protein (apoB). It is shown that the spectral peaks assigned to the methyl head groups of phosphatidylcholine and sphingomyelin in the 1H spectra of LDL exhibit line broadening when otherwise free thiol groups of apoB are covalently modified by methanethiosulfonate spin label. The effect is similar in the presence of water soluble paramagnetic compound. These results indicate that fragments of apoB, which are part of the receptor binding region, are directly in contact with the solvated phospholipid head groups of the lipid matrix. [Copyright &y& Elsevier]

A new 2-{2-[2-(4-methylphenyl)ethenyl]phenyl}pyrrole (11) was prepared and transformed by a photochemical reaction furnishing two cyclised products 4,5-dihydro-4-(p-methylphenyl)benzo[g]indole (12) and 4H-4-(p-methylbenzyl)pyrrolo[2,1-a]isoindole (13), and a reduction product, 2-{2-[2-(4-methylphenyl)ethyl]phenyl}pyrrole (14). [Copyright &y& Elsevier]

The first synthesis of 1,4,9,10-tetrahydro-4,9methanobenzo[4,5]cyclohepta[1,2-b]pyrrole (11) was achieved by the photochemical intramolecular [2 + 2] cycloaddition of N-phenoxycarbonyl- (5a and N-ethoxycarbonyl-2-[2-(2vinylphenyl)]pyrrole (6a), respectively, followed by basic hydrolysis of the isolated N-substituted 1,4,9,10-tetrahydro4,9-methanobenzo[4,5]cyclohepta[1,2-b]pyrroles (10a, 10b). Some competitively formed products were also isolated. [ABSTRACT FROM AUTHOR]

Pd(II) complexes of acyclic (1,2;4,5) and macrocyclic (3,6–10) derivatives of 1,5-bis(oxazolines), are tested in the enantioselective allylic alkylation of racemic 1,3-diphenyl-3-acetoxyprop-2-ene (14) by dimethylmalonate anion to allyl malonate derivative 15. Conformation in solution of representative allyl Pd(II) complexes 12 and 13 is studied by 2D NMR and CD spectroscopy. 2D NMR data reveal loss of C2 symmetry of the ligands in Pd(II)allyl-bis(oxazoline) complexes. CD spectra indicate distortion of the bidentate ligand in the complex and a conformationally forced larger twist between two chromophores in the macrocyclic complex. Only moderate variation of enantioselectivity with the length and ring size of the ligand is observed, and a rationale offered. [Copyright &y& Elsevier]

New furan derivatives of o -divinylbenzenes were synthesized and their photochemical reactivity has been investigated in neutral and acidic medium. Depending of the structure of the starting materials and pH value, the new cyclization (11 , 16 , 20), cycloaddiotion (12 , 13 , endo- 17 , exo- 18), electrocyclization (21 , 22) and dimeric (15 , 19) products were isolated. While photochemical investigation in neutral medium showed that the main intramolecular process is cycloaddition, in the case of acidic photochemistry, due to the protonation of the starting molecule, electrocyclization process comes to expression and formation of dihydronaphtalene products 21 and 22. Image 1 • Photoreactivity of the starting material changes upon different pH value. • The change of the heteroatom affects the course of the photochemical reaction. • Novel polycyclic photoproducts were synthesized and characterized. [ABSTRACT FROM AUTHOR]

Abstract Promising test results on biological activity of our previously described benzobicyclo[3.2.1]octadienes, obtained by intramolecular photochemical cycloaddition of o -vinylphenyl substituted butadienes, prompted us to continue with the further functionalization of this basic skeleton. Synthesis was extended to amino substituted benzobicyclo[3.2.1] octadienes starting from the chloro derivative. Novel benzobicyclo[3.2.1]octadiene benzylamines were prepared for the first time by Buchwald-Hartwig amination from the photoproduct obtained by highly efficient continuous flow-photochemistry setup. The novel amino substituted benzobicyclo[3.2.1]octadienes are especially interesting because of their methano-bridged junction of the three aromatic units at defined geometries as this gives them potential as molecular clips with very promising ADME properties due to the amino functional group. This is the first example of the Buchwald-Hartwig amination reaction on a rigid non-planar system. Graphical abstract Image 1 Highlights • First example of the Buchwald-Hartwig amination reaction on a rigid non-planar system. • Successful application of the Buchwald-Hartwig amination using BrettPhos as ligand and Pd(OAc)2 as catalyst. • Novel amino substituted benzobicyclo[3.2.1]octadienes are especially interesting because of their methano-bridged junction of the three aromatic units at defined geometries. • Promising ADME properties of the synthesized compounds due to the amino functional group. [ABSTRACT FROM AUTHOR]

In order to study the influence of heterocyclic nuclei on the photochemical behavior of conjugated butadiene systems, novel butadiene derivatives E, Z- and E, E-2/3-[4-(2-vinylphenyl)buta-1,3-dienyl]thiophene as well as E, Z- and E, E-3/4-[4-(2-vinylphenyl)buta-1,3-dienyl]pyridine have been synthesized. The Wittig reaction was utilized in a two-step reaction course. During the first Wittig reaction, the corresponding aldehydes, namely 2/3-thiophenecarboxaldehyde and 3/4-pyridinecarboxaldehyde, reacted with formylmethylenetriphenylphosphorane to give the corresponding acrylaldehydes, which reacted with the diphosphonium salt of α,α′- o-xylenedibromide in the second Wittig reaction to give new butadiene derivatives. These butadiene derivatives afforded, by photochemical intramolecular cycloaddition, new fused tricyclic as well as tetracyclic derivatives. For the first time, a study of efficiency was conducted where the efficiency of intramolecular cycloaddition of these heterocyclic butadiene derivatives was investigated by simultaneous use of ferrioxalate and valerophenone actinometers. [ABSTRACT FROM AUTHOR]

Naphtho-triazoles and thienobenzo-triazoles have so far proven to be very potent inhibitors of the enzyme butyrylcholinesterase (BChE). Based on these results, in this work, new thienobenzo-thiazoles were designed and synthesized, and their potential inhibitory activity was tested and compared with their analogs, naphtho-oxazoles. The synthesis was carried out by photochemical cyclization of thieno-thiazolostilbenes obtained in the first reaction step. Several thienobenzo-thiazoles and naphtho-oxazoles have shown significant potential as BChE inhibitors, together with the phenolic thiazolostilbene being the most active of all tested compounds. These results are significant as BChE has been attracting growing attention due to its positive role in the treatment of Alzheimer's disease. Computational examination based on the DFT approach enabled the characterization of the geometry and electronic structure of the studied molecules. Furthermore, the molecular docking study, accompanied by additional optimization of complexes ligand-active site, offered insight into the structure and stabilizing interactions in the complexes of studied molecules and BChE. [ABSTRACT FROM AUTHOR]

In this research, the synthesis, photochemistry, and computational study of new cis- and trans-isomers of amino-thienostilbenes is performed to test the efficiency of their production and acid resistance, and to investigate their electronic structure, photoreactivity, photophysical characteristics, and potential biological activity. The electronic structure and conformations of synthesized thienostilbene amines and their photocyclization products are examined computationally, along with molecular modeling of amines possessing two thiophene rings that showed inhibitory potential toward cholinesterases. New amino-styryl thiophenes, with favorable photophysical properties and proven acid resistance, represent model compounds for their water-soluble ammonium salts as potential styryl optical dyes. The comparison with organic dyes possessing a trans-aminostilbene subunit as the scaffold shows that the newly synthesized trans-aminostilbenes have very similar absorbance wavelengths. Furthermore, their functionalized cis-isomers and photocyclization products are good candidates for cholinesterase inhibitors because of the structural similarity of the molecular skeleton to some already proven bioactive derivatives. [ABSTRACT FROM AUTHOR]

Photocatalytic oxygenation of three phenyl derivatives of a bicyclic skeleton with a free double bond 1a , 1b and 1c were carried out by utilizing a cationic and an anionic manganese(III) porphyrin irradiated in the visible range. While photocatalysis of 1a and 1b led to the formation of the corresponding hydroperoxy derivatives 2 and 3 , respectively, (besides unidentified high-molecular-weight products) in the presence of the anionic Mn(III) porphyrin, the cationic photocatalyst proved to be less efficient and less selective with 1a . In the case of 1b , also with the cationic porphyrin, the corresponding hydroperoxy derivative ( 3 ) was the main product at a shorter reaction time (2 h), whereas a longer irradiation (4 h) led to the significant formation of a keto derivative ( 5 ) with a hydroperoxy substituent and a free double bond at positions deviating from those in the previous products ( 2 and 3 ). A dramatic change in the reactivity was observed for the methoxy derivative ( 1c ). It gave only traces of identifiable products by using the anionic photocatalyst, while application of the cationic Mn(III) porphyrin resulted in a relatively efficient formation of an epoxy derivative ( 6 ) due to the reaction of the isolated double bond. [ABSTRACT FROM AUTHOR]

New resveratrol–thiophene and resveratrol–maltol hybrids were synthesized as cholinesterase inhibitors and antioxidants. As with photostability experiments, biological tests also found remarkable differences in the properties and behavior of thiophene and maltol hybrids. While resveratrol–thiophene hybrids have excellent inhibitory and antioxidant properties (similar to the activity of reference drug galantamine), maltols have been proven to be weaker inhibitors and antioxidants. The molecular docking of selected active ligands gave insight into the structures of docked enzymes. It enabled the identification of interactions between the ligand and the active site of both cholinesterases. The maltols that proved to be active cholinesterase inhibitors were able to coordinate Fe3+ ion, forming complexes of 1:1 composition. Their formation constants, determined by spectrophotometry, are very similar, lgK = 11.6–12.6, suggesting that Fe3+ binds to the common hydroxy-pyranone moiety and is hardly affected by the other aromatic part of the ligand. Accordingly, the characteristic bands in their individual absorption spectra are uniformly red-shifted relative to those of the free ligands. The crystal structures of two new resveratrol–maltol hybrids were recorded, giving additional information on the molecules' intermolecular hydrogen bonds and packing. In this way, several functionalities of these new resveratrol hybrids were examined as a necessary approach to finding more effective drugs for complicated neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

A new approach to benzo[f]quinoline derivatives has been found by an effective formal [4 + 2] photocycloaddition process from novel aryl-substituted o-vinylstyryl-2-oxazoles. All of the o-vinylstyryl-2-oxazoles were synthesized by a multicomponent Wittig reaction from the diphosphonium salt of α,α′-o-xylene dibromide, formaldehyde, and 5-tolyl-, 4-phenyl-5-methyl-, and 4,5-diphenyloxazole-2-carbaldehydes. TD-DFT calculations revealed that the intramolecular photocyclization in 2-(2-vinylstyryl)oxazoles to form benzo[f]quinoline derivatives proceeds on the S1 PES via a stepwise pathway, namely by 10π followed by 6π ring closure. On that path the existence of an S0/S1 conical intersection was indicated. The reactivity of the photocyclization steps depends on the substitution pattern at positions 4 and 5 of the oxazole ring, where the aryl group in position 5 deactivates the reaction. [ABSTRACT FROM AUTHOR]

Novel butadiene derivatives display diverse photochemistry and photophysics. Excitation of 2-methyl-1-(o-vinylphenyl)-4-phenylbutadiene leads to the dihydronaphthalene derivative, whereas photolysis of the corresponding model o-methyl analogue results in the formation of the naphthalene-like derivative, deviating from the nonmethylated analogue of the prior starting compound and producing benzobi-and -tricyclic compounds. The effect of the methyl substituents is even more dramatic in the case of the dibutadienes. The parent unsubstituted compound undergoes photoinduced intramolecular cycloaddition giving benzobicyclo[3.2.1]octadiene, whereas the photochemical reaction of the corresponding dimethylated derivative shows only geometrical isomerization due to the steric effect of the substituents. Methyl groups on the butadiene backbones reduce the extent of conjugation, causing a blue-shift of the characteristic absorption band. The fluorescence efficiency is dramatically decreased, as a consequence of nonplanarity and reduced rigidity of the molecules due to the crowding by the methyl and phenyl groups together. Four molecules of very similar structures show dramatically different photoinduced behavior, revealine how changes of the nature and position of the substituents are valuable is understanding the photophysics and photochemistry of these types of compounds. [ABSTRACT FROM AUTHOR]

Abstract: Novel cis- and trans-(o-H/Me/vinyl) substituted styryl furo-benzobicyclo[3.2.1]octadiene derivatives (7a,b, 8) were prepared and transformed to the novel naphthofuran derivatives of benzobicyclo[3.2.1]octadiene (6a,b) and novel phenanthrene-benzobicyclo[3.2.1]octadiene derivative (11) by photochemical electrocyclic ring closure in the presence of iodine and by intramolecular photoinduced [4+2] cycloaddition, respectively. These novel annelated bicyclo[3.2.1]octadiene derivatives (6a,b, 11) are especially interesting for their rigid methano-bridged junction of two aromatic units at defined geometrical arrangement and thereby as potentials for molecular clips. [ABSTRACT FROM AUTHOR]

Abstract: Stilbeneylsydnone derivatives were synthesized by a sequence of reactions in good yields. Irradiation of 3-stilbeneyl-4-methylsydnone 4 gives 1H-1,2-benzodiazepine derivative 7 as the main product along with 2-methylquinoline derivative 20. Irradiation of 3-stilbeneyl-4-phenylsydnone 5 afforded only 1H-1,2-benzodiazepine derivative 8 whereas on irradiation of 4-unsubstituted 3-stilbeneylsydnone 3 no benzodiazepine derivative was detected. An efficient novel photochemical approach to 1H-1,2-benzodiazepines has been found from the new 3-(o-stilbeneyl)-4-substituted-sydnones via intramolecular 1,7-electrocyclization reaction of the photogenerated nitrile imines. [ABSTRACT FROM AUTHOR]

Abstract: Novel 1-(o-vinylphenyl)-4-(phenyl/2-furyl) butadienes (4a,b), synthesized in one step, undergo intramolecular photocycloaddition reaction to benzobicyclo[3.2.1]octadiene derivatives (6a,b) in very good yield (70–90%). In the case of phenyl derivative (4a) only endo-phenyl-benzobicyclo[3.2.1]octadiene isomer (endo-6a) was isolated whereas the furan (4b) derivative resulted in a mixture of endo- and exo-bicyclic isomer (6b). Phenyl benzobicyclo[3.2.1]octadiene derivative (endo-6a) underwent further di-π-methane rearrangement leading to tricyclic structure (endo-7a). The isolated compound 6a and the product of the rearrangement endo-7a were characterised by X-ray structure analysis. [Copyright &y& Elsevier]

Abstract: New β,β′-aryl/heteroaryl 2,3-divinylfuran derivatives (9a–d) in which a hexatriene system is a part of heteroaromatic ring have been synthesized and their photochemical properties were investigated. The primary process observed was the isomerization to trans,trans-isomers 9a–d followed by photochemical rearrangement of the furan ring giving the phototransposition products (I–IV). Stilbenes (20, 21) and phenanthrenes (22, 25, and 26), formed as secondary products from the competitive intermolecular cycloadditions, were also observed. [Copyright &y& Elsevier]

Three new Pd(II) complexes, i.e. [PdCl2L]2 (A), PdCl2L2 (B) and [Pd(μ-Cl)(L-H)]2 (C), each with two diethyl [α-(4-benzenazoanilino)-2-hydroxybenzyl]phosphonates (L) bound to either one or two palladium atoms, are synthesized and characterized by elemental analysis, by IR, UV–vis and solid-state 13C-NMR spectra. Complexes B and C are additionally characterized by 1H-, 13C- and 31P-NMR and electrospray mass spectrometry (ESMS) studies using dimethylformamide (DMF) as a solvent. In DMF solution adducts A and B undergo spontaneous rearrangement into the cyclopalladated complex C. Dynamic 1H-NMR study of this rearrangement as well as of the reactions of L with PdCl2 and Na2PdCl4 revealed a complex equilibrium in DMF solutions and enabled the formation mechanism of all involved species to be resolved. The complex A is immediately solvolyzed producing two molecules of intermediate M [PdCl2(L)(DMF)]. Complex M was also the first intermediate in the reaction of L with PdCl2. Once present in concentration above 10−5 mol dm−3 M dimerizes very fast into chloro-bridged dimer [PdCl(μ-Cl)(L)]2 (D) which undergoes cyclopalladation and converts into the complex C. The formation of C from the intermediate D is clearly demonstrated by the concentration dependence of the cyclopalladation reaction which has order greater than one. Chloride ions, released by cyclopalladation, react with D by splitting chloro-bridge and binding to metal atoms to produce byproduct [PdCl3(L)]− (T). The same species T are formed in the reaction of L with Na2PdCl4 whereby a chloride ion is replaced by the ligand L. The complex B undergoes similar, but slower, solvolytic reaction producing M and L while further reaction steps are identical as in the solvolysis of A. [Copyright &y& Elsevier]

We present a double-stranded ferrocene pseudopeptide 2b which exhibits stimuli responsive chirality inversion triggered by solvent exchange or acid addition. Compound 2b exists as a mixture of self-assembled fast exchanging oligomers which macroscopically behave as a chiroptical switch with two stable states. The ferrocene group inversion results in a distinct CD signal in the visible part of the spectrum. The inversion is accomplished through a conformational change due to a rearrangement of hydrogen bonding forcing the rotation of ferrocene rings. [ABSTRACT FROM AUTHOR]

A new synthetic approach is presented for the synthesis of naphthoxazoles and fused heterobenzoxazoles. The starting 5-(aryl/furyl/thienyl/pyridyl ethenyl)oxazoles are prepared from the corresponding α,β-unsaturated aldehydes using Van Leusen reagent in very good yields and are transformed into naphthoxazoles and fused heterobenzoxazoles on irradiation under aerobic conditions and in the presence of iodine. [ABSTRACT FROM AUTHOR]

Stilbene analogues with the pyridine ring, that is di-(pyridin-2/3/4-yl)vinyl)benzenes, were synthesized, purified and completely spectroscopically characterized. Upon irradiation these di-(pyridin-3/4-yl)vinyl)benzenes showed no other process but isomerization, in conditions for both intra- and intermolecular reactions. Compound di-(pyridin-2-yl)vinyl)benzene gave by intermolecular cycloaddition reaction, in trace amounts, a dimeric product. This general unreactivity towards photocyclization and photocycloaddition reactions led to further investigations and description of photophysical properties. Quantum yields of photolysis as well as fluorescence were measured and calculated. It was shown that the placement of the nitrogen in the stilbene like system plays an important role in the photophysical properties. The connection between photophysical properties and configurational isomerism was defined. The polarity effect of the medium has a complex influence on the photobehaviour and the measured effects are probably not coming only from polarity. [ABSTRACT FROM AUTHOR]

Promising test results on the biological activity of our previously described naphtho[1,2‐d]oxazoles and heterobenz[1,2‐d]oxazoles, obtained by the photochemical cyclization of 5‐phenylethenyl‐ and 5‐heteroarylethenyloxazoles, prompted us to continue with the photochemical synthesis of substituted naphtho[1,2‐d]oxazoles, and to extend the photochemical cyclization to the synthesis of naphtho/heterobenz[2,1‐d]oxazoles from 4‐(aryl/heteroarylethenyl)oxazoles. The required p‐ and o‐phenyl‐substituted 5‐arylethenyloxazoles were prepared from the corresponding α,β‐unsaturated aldehydes and the TosMIC reagent (tosylmethyl isocyanide) by the Van Leusen reaction. The substituted 4‐(aryl/heteroarylethenyl)oxazoles were prepared by the Wittig reaction starting from various phosphonium salts and 2‐H/methyl‐4‐oxazolecarbaldehydes. [ABSTRACT FROM AUTHOR]

To study the effects of the position of the hexatrienyl moiety on the oxazole ring, novel substituted cis/trans-2/4/5-(2-vinylstyryl)oxazoles have been synthesized. These novel compounds were prepared by Wittig reaction from the diphosphonium salt of α,α'-o-xylenedibromide, formaldehyde and the corresponding 2-methyl-4-, 4-methyl-2-, 2-pheny-5- and 4-methyl-5-oxazolecarbaldehyde, respectively. Aldehydes were synthesized by using several synthetic approaches. By applying intramolecular photocycloaddition, 2-methyl-4-(2-vinylstyryl)-oxazole afforded, as major product, fused oxazoline-benzobicyclo[3.2.1]octene with small quantities of 4-(1,2-dihydronaphthalen-2-yl)-2-methyloxazole, as electrocyclization product. Upon irradiation of 4-methyl-5-(2-vinylstyryl)oxazole, endo- and exo-benzobicyclo[2.1.1]hexene products were formed by [2+2] cycloaddition; this was the first instance of the 1,4-closure to the bicyclo[2.1.1]hexene skeleton in the 2-, 4-, and 5-oxazole- stilbene derivatives studied so far. Derivatives 2-phenyl-5- and 4-methyl-2-(2-vinylstyryl)oxazole did not react and gave only high-weight molecular products but were crucial as a comparison in the overall mechanistic study. We have found that, depending on the position of the hexatrienyl moiety in the oxazole ring, as well as on the position of the methyl/phenyl substituents, these new vinylstyryl-2/4/5-oxazole derivatives show diverse photochemical behavior. [ABSTRACT FROM AUTHOR]

A non-covalent self-assembled chiral alanyl aminopyridine ligand exhibits supramolecular chirality in solution, independent of the organic solvent used. The supramolecular chirality of the assemblies is completely inverted by complexation to zinc ions. To date, such a supramolecular metal–ligand system has not been reported in the literature. [ABSTRACT FROM AUTHOR]

Highlights: [•] Initial mono- and dichloro-substituted butadienes display diverse photobehaviour. [•] α-Chloro derivatives react in the sense of electrocyclization reaction. [•] p-Chloro-substituted butadienes undergo intramolecular photocycloaddition. [•] Competitive effects of chlorine substituents on the photoinduced behaviour. [ABSTRACT FROM AUTHOR]

Abstract: The stereochemical outcome of reaction of 2,5-bis-trifluoromethyl-1,3,4-oxadiazole with 7-oxanorbornenes under various conditions was investigated. For the first time, microwave irradiation in carrying this type of reactions was used, resulting in comparable yields in significantly shorter reaction times. Regardless on substrate, in all reactions mixtures of the two isomeric O 3-[3]polynorbornanes, bent and linear were obtained, with slight preference for bent structure. In some cases, retro Diels–Alder fragmentation was observed resulting in formation of isobenzofuran species. Reaction mechanism was also studied computationally (RHF/6-31G* method), and the origin of stereoselectivity explained by repulsive lone pair interactions between oxygen bridges in the transition state of the 1,3-dipolar addition. [Copyright &y& Elsevier]

Abstract: Norbornene building BLOCKs formed by the reaction of porphyrin 1,3-dienes with norbornadiene or dimethyl tricyclo[4.2.1.02,5]nona-2,7-diene-3,4-dicarboxylate were coupled with an ester-activated cyclobutene epoxide BLOCK to afford the first examples of hinged porphyrin-spacer-acceptor dyads. Similar dual coupling with a bis-(cyclobutene epoxide) formed doubly hinged POR-spacer-POR scaffolds separated by up to 16σ-bonds. The ability of the doubly hinged ZnPOR-16σ-ZnPOR scaffold to adopt cavity-shaped conformations was indicated by semiempirical AM1 calculations of these conformationally flexible bis-porphyrin scaffolds. [Copyright &y& Elsevier]

Abstract: New β-3-thienyl (8) and β-3-furyl derivatives of o-divinylbenzene (9) have been synthesised and their photochemical behaviour compared with 2-thienyl (7) and 2-furyl derivatives (2). Whereas the β-(2-heteroaryl) substituted o-divinylbenzenes (7 or 2) give only bicyclo[3.2.1]octadiene structure (14 or 1) by 1,6-ring closure of the biradical intermediate, β-(3-heteroaryl) substituted o-divinylbenzenes (8 or 9) give bicyclo[3.2.1]octadiene structure (23 or 24) and bicyclo[2.1.1]hexene structure (25 or 26) by 1,6- and 1,4-ring closure, respectively. This photochemical approach provides a simple method to 2,3- and 3,2-fused thiophene and furan polycyclic compounds. [Copyright &y& Elsevier]

From the irradiation mixture of N-acetyl-2-styrylpyrroles (5a, b) the deacylated (6a, b), phototransposition (7a, b–10a, b), electrocyclisation (12), addition and reduction (11, 13 and 14) and dimerisation products (15) have been detected. No intramolecular cycloaddition products have been observed. [Copyright &y& Elsevier]

The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) by organophosphates (OPs) as nerve agents and pesticides compromises normal cholinergic nerve signal transduction in the peripheral and central nervous systems (CNS) leading to cholinergic crisis. The treatment comprises an antimuscarinic drug and an oxime reactivator of the inhibited enzyme. Oximes in use have quaternary nitrogens, and therefore poorly cross the brain–blood barrier. In this work, we synthesized novel uncharged thienostilbene oximes by the Wittig reaction, converted to aldehydes by Vilsmeier formylation, and transformed to the corresponding uncharged oximes in very high yields. Eight trans,anti- and trans,syn-isomers of oximes were tested as reactivators of nerve-agent-inhibited AChE and BChE. Four derivatives reactivated cyclosarin-inhibited BChE up to 70% in two hours of reactivation, and docking studies confirmed their productive interactions with the active site of cyclosarin-inhibited BChE. Based on the moderate binding affinity of both AChE and BChE for all selected oximes, and in silico evaluated ADME properties regarding lipophilicity and CNS activity, these compounds present a new class of oximes with the potential for further development of CNS-active therapeutics in OP poisoning. [ABSTRACT FROM AUTHOR]

• New hexatriene systems with arylbutadiene unit(s), substituted with F, N(CH 3) 2 or NO 2 group(s) were synthesized. • Diverse photochemistry and photophysics of derivatives were established and explained. • The primary photochemical step for each compound is a fast cis-trans isomerization. • In some cases intramolecular cycloaddition gave photoproducts with bicyclo[3.2.1]-skeleton. • Computational investigation of energy profiles of Wittig reaction gave rationalization of stereochemistry. Novel p -fluoro, p -dimethylamino and p -nitro substituted arylbutadiene derivatives were synthesized by Wittig reaction and their diverse photochemistry and photophysics were established and explained. Under excitation mono- and difluoro derivatives undergo photoinduced intramolecular cycloaddition. The parent mono-dimethylamino substituted derivative undergoes the same reaction type giving the photocycloadduct in lower yield and with incomplete consumption, whereas its bis(dimethylamino) analogue shows only geometrical isomerization due to the steric effect of the substituents. Mono- and dinitro derivatives show photochemical unreactivity. Conjugated analogues with similar structures display dramatically different photoinduced behavior, revealing how changes of the nature of substituents impact their photophysics and photochemistry. The computational investigation of the effects of the conformational diversity within the steric influence of the starting geometric isomers on the photoreaction pathway and energy profiles of the Wittig reaction is performed for the first time. [ABSTRACT FROM AUTHOR]

Promising test results on biological activity of our previously described benzobicyclo[3.2.1]octadienes, synthetically obtained by intramolecular photochemical cycloaddition reaction, prompted us to pursue with the further functionalization of this basic skeleton toward oxime derivatives. The free energies of formation of complexes between planned new oximes showing promising ADME properties and the active sites of cholinesterases were calculated using docking and density functional theory, showing that thermodynamical stability of some of the examined complexes is the same as the stability of the complex formed with well known and efficient cholinesterase inhibitor huperzine A. On the basis of calculated stabilities of complexes, the synthesis of several representative new compounds was succesfully performed. In some cases, the furan ring opened on two different ways so different opened oximes and oxime ethers were also formed. All new prepared oximes and oxime ethers present good material for further experimental investigation as inhibitors/reactivators of cholinesterases. Image 1 • The stabilities of complexes between oximes and cholinesterases were calculated by DFT. • On the basis of calculations synthesis of new compounds was performed. • Oximes and oxime ethers will be explored as potential inhibitors of cholinesterases. [ABSTRACT FROM AUTHOR]