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Chemia bioortogonalna : nowa perspektywa dla chemii organicznej

Miszczak K.

Wiadomości Chemiczne

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2018

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[Z] 72, 9-10

703--722

EN

This work is about bioorthogonal chemistry as a chemistry of reactions taking place in the living, in particular human, organism environment. In the search for reactions that can occur under conditions, the focus is mainly on the reactions of molecules that do not occur naturally in the body. Then, to have any application, generally for the purpose of using this reactions to locate the accumulation spotes of the selected substance, one molekule is covalently bonded to the biomarker molecule, the second binds to the indicator molecule, which is frequently fluorescein. Among a numerous examples of reactions that were designed during the short history of bioorthogonal chemistry, there are mainly reactions involving organic azides, which are not naturalny present in the human body. An example of such a reaction is the Staudinger ligation. Subsequent modifications include mainly the 1,3-dipolar addition of azides to alkynes, catalyzed by copper(I) ions. The instability and toxicity of this catalyst has forced further innovations in bioorthogonal reactions. One of them is the use of alkynes with high angular stress, which causes a significant reduction in the activation energy of the process, that it is unnecessary to use a catalyst. Another example of the bioorthogonal reactions are Diels-Alder reactions. The interest in these reactions is not diminishing for several reasons. One of them is the fact that as a result of a simple reaction two new carbon-carbon bonds (or others, for the HDA reaction) occur. Furthermore, many of these reactions occur at standard temperature, without additional heating. Moreover, the possibility of numerous modifications of the skeleton and functional groups and the substituents of dienes and dienophils facilitates carrying out these reactions in the aquatic environment. At the end, the article presents examples of the application of cyclooaddition reactions in bioorthogonal chemistry.

2

Diazafluorene in 1,3-dipolar cycloaddiction reactions: short review

Kula K., Łapczuk-Krygier A.

Technical Transactions

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2018

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Vol. 115, iss. 6

41--53

EN

This review is an attempt to systemise knowledge within the field of 1,3DC reactions of diazafluorene with different dipolarophiles. This paper is arranged according to the dipolarophile structure. We are hoping that this review can help organic chemists who deal with the preparation of five-membraned heterocycles.

PL

Niniejszy przegląd stanowi próbę usystematyzowania stanu wiedzy w obszarze reakcji 1,3DC diazafluorenu z różnymi dipolarofilami. Materiał został uporządkowany na podstawie budowy dipolarofila. Mamy nadzieje, iż przegląd będzie pomocny chemikom organikom zajmującym się preparatyką związków heterocyklicznych.

3

Evaluation on Curing Properties and Kinetics of Isophthalonitrile Oxide

Fan Y., Tang C., Hu Q., Lei Y., Huo J.

Polish Journal of Chemical Technology

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2018

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Vol. 20, nr 3

37--46

EN

N,N-dihydroxybenzene-1,3-dicarboximidoyl dichloride was synthesized from benzene-1,3-dicarboxaldehyde and characterized by fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance 1H and 13C NMR). The elastomer was prepared through the 1,3-dipolar cycloaddition of reaction between liquid polybutadiene (LPB) and isophthalonitrile oxide in this work. The tensile strength of different elastomer was enhanced from 0.14 MPa to 0.33 MPa as the elongation at break decreased from 145% to 73%, and the modulus increased from 0.09 kPa to 0.47 kPa. The parameters of kinetic indicated that the curing reaction was first order reaction and the apparent activation energy of each curing system was less than 10.10 kJ/mol when the content of N,N-dihydroxybenzene-1,3- dicarboximidoyl dichloride was increased from 7% to 12%. These results suggested that nitrile oxides achieved curing of polymer binders at room temperature and this work had definite guiding significance for the application of nitrile oxides in polymer binders.

4

Izoksazolidynowe analogi nukleozydów

Kokosza K., Piotrowska D. G.

Wiadomości Chemiczne

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2012

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[Z] 66, 11-12

1041-1070

EN

Compounds having isoxazolidine moiety are of special interest since they show a broad spectrum of biological activity, including anticancer [1–5], antiviral [6], antibacterial [7–9] and antifungal activities [9–12]. Extensive studies on isoxazolidine moiety containing compounds resulted in discovery of several potentially antiviral and anticancer drugs (e.g. pyridemine-A 1 [2, 3], as well as isoxazolidines substituted with thymine and 5-fluorouracil 52a (AdT) [38–40] and 59 [(–)-AdFU] [41–43], respectively). In this review the most spectacular examples of the synthesis of isoxazolidine analogues of nucleosides are discussed and their biological activity is emphasized.

5

Wykorzystanie reakcji 1,3-dipolarnej cykloaddycji Huisgena do modyfikacji nukleozydów i ligonukleotydów

Radzikowska E.

Wiadomości Chemiczne

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2011

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[Z] 65, 3-4

207-234

EN

The 1,3-dipolar cycloaddition reaction between azides and terminal alkynes, known as the Huisgen reaction, constitutes a powerful tool for the synthesis of versatile molecules containing carbon – heteroatom bond. The use of a copper(I) salt in this reaction allowed Sharpless to develop the concept of „click chemistry” [1]. This strategy is based on reactions between small units characterized by mild reaction conditions, versatility, high yields and stereospecificity. The chemistry of nucleic acids and nucleoside analogues is undergoing rapid developments and numerous compounds from these classes of compounds are used in medicinal treatment. Analogues of nucleoside constitute a class of drugs that possesses either anticancer or/and antiviral activity (against HIV, HSV, VZV or HCV viruses) [3]. Many modified oligonucleotides show biological activity. As potential drugs oligonucleotides are employed in antisense, antigen and aptamer strategies. An antisense therapeutic agent acts on the pathogenic mRNA causing inactivation of the target whereas an antigen agent acts on DNA and aptamer on unwanted protein. It is not surprising that number of research groups are trying to join the concept of click chemistry with nucleic acids chemistry. In this way, it is possible to obtain new molecules like base- or sugar-modified nucleosides, nucleosides, bioconjugates and olignucleotides. The copper-catalyzed 1,3-dipolar cycloaddition CuAAC allows to functionalize DNA, for example by labelling it through attaching small molecules to DNA. Two general strategies have been developed for this purpose: presynthetic and postsynthetic labelling. In the presynthetic method nucleotide monomers are labelled before DNA synthesis and purification. In the postsynthetic strategy DNA containing small reactive groups is synthesized first and then it is conjugated with the desired molecules. CuAAC is also a convenient method for the synthesis of modified oligonucleotides in which phosphodiester linkage is replaced by 1,2,3- -triazole or for a solid phase synthesis. Such molecules appear to be useful in medicine, molecular diagnostic (e.g. fluorescent dyes) or mechanistic molecular model in the future.

6

Synthesis of the Potential Mannosidase Inhibitor via 1,3-Dipolar Cycloaddition Involving Cyclic Nitrone and Unsaturated Chiral gamma-Lactone

Stecko S., Paśniczek , K., Jurczak M., Solecka J., Chmielewski M.

Polish Journal of Chemistry

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2009

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Vol. 83, nr 2

237-243

EN

The 1,3-dipolar cycloaddition of cyclic nitrone derived from tartaric acid with (S)-5-hydroxymethyl-2(5H)-furanone leads to a single adduct which was transformed into 1,2,6,7-tetrahydroxy-2-hydroxymethyl-indolizidine via reaction sequence involving protection of the hydroxymethyl group, reduction of the lactone moiety, protection of the resulting diol, and the N-O hydrogenolysis followed by the intramolecular alkylation of the nitrogen atom.

7

[2+3]-Cycloadditions of Diazoalkanes with Imines of Hexafluoroacetone and Chloral

Mloston G., Bodzioch A., Cebulska Z., Linden A., Heimgartner H.

Polish Journal of Chemistry

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2007

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Vol. 81, nr 5-6

631-641

EN

The reactions of N-arylimines 1 and 2 of hexafluoroacetone and chloral, respectively, with diazoalkanes at –60C to room temperature led to the corresponding 4,5-dihydro- 1H-[1,2,3]triazoles 4 and 5, in a regioselective [2+3]-cycloaddition. The structure of one example in each case has been established by X-ray crystallography. The thermal decomposition of these adducts yielded the corresponding aziridines, bearing two trifluoromethyl and one trichloromethyl group, respectively, at C(2).

8

Chemoselectivity of the [2+3]-Cycloaddition of Thiocarbonyl Ylides with 5-Benzylidene-3-phenylrhodanine

Seyfried M., Linden A., Mlostoń G., Heimgartner H.

Polish Journal of Chemistry

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2006

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Vol. 80, nr 8

1363-1376

EN

Reactions of three different thiocarbonyl S-methylides, generated from thiobenzophenone (2), 2,2,4,4-tetramethyl-3-thioxocyclobutanone (3), and adamantanethione (8), respectively, and diazomethane, with 5-benzylidene-3-phenylrhodanine (12) were carried out. The aromatic thiocarbonyl ylide 1a adds chemoselectively to the C,C-double bond, but the spirocyclic 1,3-dithiolane 18, i.e. the [2+3]-cycloadduct with the C=S group of 12,was also formed as a minor product. In the cases of the aliphatic thiocarbonyl ylides 6 and 20, the [2+3]-cycloaddition occurred at the exocyclic C,C-double bond exclusively to give the spirocyclic tetrahydrothiophene derivatives 23 and 21, respectively. Asmooth acid-catalyzed decomposition of 18 yielded the 2-diphenylmethylidene derivative 19. The formation of product 24, which was obtained in the reaction of the sterically congested ylide 6 with 12, is explained by a 1,4-H-shift in an intermediate zwitterionic adduct. The structures of the tetrahydrothiophenes 17, 21 and 23, as well as that of 24, were established by X-ray crystallography.

9

Click chemistry - czyżby rewolucja w syntezie organicznej?

Kacprzak K.

Wiadomości Chemiczne

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2005

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[Z] 59, 7-8

583--611

EN

In 2001 prof. K.B. Sharpless from Scripps Institute has announced a new idea for an easier and faster molecular discovery, named click chemistry. This concept bases on the following observations: -currently organic chemists invest too much effort in assembling the structure, although it is the function that is sought. The function can be also found in molecules that are more easy to synthesise. -nature prefers carbon-heteroatom bond formation and most biomolecules are formed from small building blocks containig and connected by such bonds. Thus, the focus should be given to the efficient carbon-heteroatom bond formation. -estimated pool of potential drug-like molecules (<500 Da, <30 non-hydrogen atoms, only C, H, O, N, S, P, F, Cl, Br, stable at room temperature, in the presence of water and air) is between 1062-1063. This is the space for exploration. Click chemistry embraces therefore a set of powerful! reactions which must be modular, wide in scope, highly yielding, generating easily removable byproducts (with no need for chromatographic purification) and stereoselective. These reaction should be also insensitive to oxygen and water and preferably carried out under simple conditions. Click reactions achieve their efficienty due to the high thermody-namic driving force, usually greater than > 20 kcal/mol (thus can be recognized as spring-loaded for a single trajectory). Examples of these reactions include: nucleo-philic opening of strained rings (epoxides, aziridines), cycloadditions (e.g. 1,3-di-polar or Diels-Alder type reaction), additions to carbon-carbon multiple bond (epo-xidation, dihydroxylation, Michael addition) and some types of carbonyl chemistry . An illustration of this concept is multigram 4-step synthesis of products 2a and 2b (Scheme 2) without the use of chromatography. Click chemistry idea was discussed in detail by Sharpless in [1] and [4]. Huisgen 1,3-dipolar cycloadditon is cream of the crop of various click reactions and was used in many notable applications of click chemistry concept, high-ligh-ted in this review. This reaction is strongly thermodynamically activated (35-50 kcal/mol), modular and of wide scope, it shows also perfect atom economy and provides products with high yield after usually simple workup. Moreover, due to the stability of reactants and 1,2,3-triazoles to various reactions conditions, including oxygen and water, this cycloaddition can be carried out in water. Target guide synthesis combined with 1,3-dipolar Huisgen reaction was used for finding new, most potent (active in femtomolar concentration) acetylcholine este-rase inhibitors and carbonic anhydrase inhibitors 5a,b. Other inhibitors developed by synthesis and screening of 1,2,3-triazole libraries include a-l,3-fukosyltransferase VI, HlV-prote-ase. 1,3-Dipolar cycloaddition was also used for modification of antibiotic tyrosidine and vancomycine and the modified products 10a,b and 11a,b exhibit better therapeutic index and activity respectively. Important applications of Huisgen reaction in molecular biology include bioconiugation and labeling techniques. Cowpea virus was efficiently labeled by fluorescein derivatives and cell surfaces were decorated by various biotin derivatives using appropriate azide-alkyne components. Click chemistry in this field was also used for designing new methods for labeling protein, in vitro or in vivo protein profiling (Scheme 11) [27] and DNA sequencing. Many important applications of 1,3-Huisgen cycloaddition are found in material chemistry. These include efficient synthesis of dendrimers wihout the use of chromatography ordendronised polymers. 1,2,3-Triazole linker formation was utilised for functionalisation of poly(norbornenes), modular copolymer synthesis and silicon waffers or gold surface modification. 1,3-Dipolar cycloaddition was also used in the synthesis of new fluorescent cumarines 54, two-photon absorption chromophores 55 and water-soluble calixarenes 56. Huisgen reaction was recently widely explored for modification of natural products and biomolecules and many interesting 1,2,3-triazole derivatives of sugars, aminoacids and peptides, lipids, steroids and alkaloids were synthesised (62-74). In summary, in a relatively short period of time after its introduction, click chemistry concept was widely approved in various areas and resulted in many important applications. Thus it can be regared as a versatile toolbox for "production of molecular properties".