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Methylenecyclopropanes (MCPs) are easily accessible yet highly strained and reactive building blocks. MCP can be readily opened under transition metal or Lewis acid catalyzed conditions. We have hypothesized that a highly polar and Lewis acidic reaction medium could facilitate the ring opening of MCPs with simple nucleophiles. We have recently shown that liquid sulfur dioxide perfectly fulfils the aforementioned solvent requirements. Additionally, it dissolves well inorganic salts. Here we report ring opening of MCPs in liquid SO2 with I and II group metal halides.

In recent years, many applications of SO2 and its surrogates in organic synthesis have been reported. This has prompted us to search for organic reactions that would profit from their running in liquid SO2 as a reaction medium

Methylenecyclopropanes (MCPs) are easily accessible yet highly strained and reactive building blocks. MCP can be readily opened under transition metal or Lewis acid catalyzed conditions. We have hypothesized that a highly polar and Lewis acidic reaction medium could facilitate the ring opening of MCPs with simple nucleophiles. We have recently shown that liquid sulfur dioxide perfectly fulfils the aforementioned solvent requirements.

Methylenecyclopropanes (MCPs) are easily accessible yet highly strained and reactive building blocks. MCP can be readily opened under transition metal or Lewis acid catalyzed conditions. We have hypothesized that a highly polar and Lewis acidic reaction medium could facilitate the ring opening of MCPs with simple nucleophiles. We have recently shown that liquid sulfur dioxide perfectly fulfils the aforementioned solvent requirements.

New C-C bond formation from alcohols via Lewis acid catalysis is atom-economical method to afford valuable synthetical building blocks. Liquid SO2 previosly has been demonstrated as highly polar Lewis acid solvent suitable for carbcation intermediate reactions. In such manner, we have indulged ourselves for study of substituted ketone and vinyl halide synthesis from alkynes with transition metal Lewis acid catalysis in liquid SO2 medium.

Earlier we reported the synthesis of fluorescent 6-triazolyl purine nucleosides and the synthesis of 2/6-triazolyl purine derivatives with amorphous groups at N(9) position. Different electron-donor and electron-acceptor groups were introduced in the purine structure that changed the fluorescent properties, while the trityl group increased amorphous properties and carbazole groups enhanced hole transport capabilities.

Metilēnciklopropāni (MCP) ir viegli sintezējamas molekulas, kas ir vērtīgi būvbloki organiskajā sintēzē. Pēdējos gados liela uzmanība pievērsta MCP ciklu atvēršanai izmantojot Luisa skābes katalizatorus. Mēs demonstrējam sēra dioksīdu kā unikālu šķīdinātāju, kas ļauj veikt MCP atvēršanu ar I grupas metālu halīdiem.

It was discovered that 2,4-diazidoquinazoline in solution exists in a tautomeric equilibrium. The tetrazole – azide tautomerism of azidoquinazolines was studied since 1960s, however, its application for 2,4-derivatization of quinazolines is underexplored. For the first time the molecular structure of 5-(piperidin-1-yl)tetrazolo[1,5-a]quinazoline was proved by X-ray diffraction analysis. We have also shown that obtained 5-amino derivatives undergo CuAAC reaction with terminal alkynes to give novel quinazoline derivatives.

Earlier we reported the synthesis of fluorescent 6-triazolyl purine nucleosides. We have developed the synthesis of 2/6-1,2,3-triazolyl, 2-imidazolyl, 2-(1,2,4-triazolyl) and 2-tetrazolyl purine derivatives with amorphousing groups at N(9) position.

Although the dominant propargyl silane reaction pathway is Hosomi-Sakurai type addition, there are some reports of rearrangement reactions in the intermediate carbenium ions.1 Now we report a novel way of inducing silyl group migration and describe two endgame scenarios for the reactive intermediates.

Azolylpurines and azolylpurine nucleosides have important medicinal and biological applications. We have developed a novel approach for the synthesis of C(2) and C(6) modified purines and purine nucleoside analogues.

Here we report design and synthesis of fluorescent purine derivatives with amorphous properties and their potential applications in the OLED technology. For this purpose, we have introduced different five-membered heterocycles and piperidine at C6/C2 positions of purine and different amorphous groups at N9 position. We used boric acid derivatives to obtain furan-3-yl, thiophen-2- yl and thiophen-3-yl compounds and simple SNAr procedure for imidazolyl, 1,2,4-triazolyl and tetrazolyl compounds. All synthetic routes were elaborated from the 2,6-dichloropurine by varying sequences of Mitsunobu, SNAr, Suzuki and cyclization reactions. The final products were obtained with different regioselectivity in 74-86% yields.

Earlier we reported the synthesis of fluorescent 6-triazolyl purine nucleosides [1]. Now we have developed the synthesis of 2/6-triazolyl purine derivatives with amorphousing groups at N(9) position. Different electron-donor and electron-acceptor groups were introduced in the purine structure and their modulating influence on fluorescent properties was studied.

Betulin is an abundant naturally occurring triterpene, most commonly found in birch bark. Research shows, that betulin and its derrivatives possess wide spectrum of biological activities such as anti-HIV, antiinflammatory and anticancer [1,2]. Use of betulin is limited by its low solubility in water. Therefore, to improve properties of betulin, structural modifications with new biological activity simultaneously improving solubility in water are being made [3].

Here we report the use of strong Brønsted acids such as triflic acid to protonate the triple bond in propargyl silanes. Resulting β-silyl vinyl carbenium ion undergoes 1,2-silyl shift to give more stable β-silyl allyl carbenium ion. Protodesilylation is largely suppressed by usage of bulky silyl groups. Allyl carbenium ions generated from terminal propargyl silanes undergo deprotonation to give silyl dienes. For 1-aryl propargyl silanes a competing intramolecular Friedel-Crafts alkylation in the intermediate carbenium ion is observed.

Synthesis of substituted triazolyl purines with linkers at N(9) position is described. Introduction of electron-donor and electron-acceptor groups in purine ring provide fluorescent properties.

Ritter reaction between alcohols and nitriles is facilated by the use of liquid sulfur dioxide (SO2) as a reaction solvent. New indium (III) triflate (In(OTf)3) catalyzed conditions were developed and applied for various substrates to form corresponding amides in good to excellent yields. Furthermore, unactivated secondary alcohols that generate relatively less stable carbenium ions gave the best isolated yields known to date. Liquid sulfur dioxide as a solvent is also found to be effective in other transformations like catalyst-free glycosylation and alkyne hydration that is now under investigation in our laboratory.

In the field of organic chemistry SO2 is used as a solvent, catalyst and a reagent [1]. It has a broad liquid range (from -75 °C to -10 °C) and due to the high dipole moment (1.6 D) it has high solvation power for ionic and covalent compounds. By dissolving inorganic and organic substances in liquid SO2 it is possible to perform SN2 type reactions, including nucleophilic ring opening of small N-heterocycles under mild reactions conditions described by us [2].

In recent years many applications of SO2 and its crystalline surrogates in organic synthesis have been reported.1 This has prompted us to search for organic reactions that would profit from their running in liquid SO2 as a reaction medium.

Sila-ēnu un bora-ēnu reakcijas ar SO2 un to pielietojums sulfoksīdu un sulfonu sintēzē

Aziridine and azetidine moieties are important small ring N-heterocycles in organic synthesis due to their biological and pharmacological properties and synthetic potential as the building blocks [1]. Modifications of these aza-heterocycles can lead to the formation of various useful compounds, such as heterocycles [2], alkaloids [3] and non-natural amino acids [4].

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for cleavage of extracellular matrix proteins. Because of their effect on both physiological and pathological processes, MMPs, especially MMP-2, have become interesting targets for treatment of cancer. Herein we report potency of MMP-2 inhibition among aziridine and azetidine derivatives containing 1,4- or 1,5- disubstituted triazoles in the side chain.

Aziridine and azetidine moieties are important small ring N-heterocycles in organic synthesis due to their biological and pharmacological properties and synthetic potential as a building blocks. Here we present a new synthetic process of aziridine and azetidine NRORs with metal halides and other nucleophiles in liquid sulfur dioxide.

From Methallylsilanes to Methallyl Sulfoxides

We have prepared composites containing different amounts of hydroxyapatite and biodegradable polymers, both non-modified and chemically modified.

Aziridine and azetidine moieties are important small ring N-heterocycles in organic synthesis due to their biological and pharmacological properties and synthetic potential as a building blocks. Modifications of these aza-heterocycles can lead to the formation of various classes of compounds, such as heterocycles, alkaloids and non-natural amino acids.

Here we present a new synthetic process of aziridine and azetidine NRORs with metal halides and other nucleophiles in liquid sulfur dioxide.

From Methallylsilanes to Methallylsulfoxides: Application of Sila-ene Reaction of Sulfur Dioxide

Herein we report a synthetic method towards variously substituted methallylsulfoxides 1. General approach includes organometallic addition to trimethylsilyl methallylsulfinate 2.

Sulfur dioxide, which is a gas at ambient conditions, reveals a rather long liquid range: it boils at -10 °C and freezes at -75.5 °C. Most importantly, SO2 condenses easily by compression due to its high critical temperature (157.35 °C, 7.88 MPa) and its phase diagram predicts only ~10 atm pressure at 60 °C in a closed reactor.Sulfur dioxide has a high dipole moment (1.61 D), therefore it readily can dissolve both organic and inorganic salts.

We report the use of 2,6-bis-triazolylpurine nucleoside and 2,6-diazidopurine nucleoside in the nucleophilic aromatic substitution reactions with different arylthiols.

Ritter reaction is associated with a one-pot process for amide bond formation, that involves nitrile and a group, capable of giving a relatively stable carbenium ion (originally - alcohol or alkene) in strongly ionizing acidic medium.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for cleavage of extracellular matrix proteins such as collagen, gelatin, elastin and casein. Because of their effect on both physiological and pathological processes, MMPs have become interesting targets for treatment of cancer. In addition, it is known that MMP-2 has the most important impact to tumour growth. Previously, our research group has identified aziridine derivatives with 1,4-disubstituted 1,2,3-triazole in the side chain as a new class of MMP-2 inhibitors.2,3 Herein we report futher investigation of these aziridine derivatives as well as new research among aziridines containing 1,5-disubstituted 1,2,3-triazole and azetidines containing 1,4-disubstituted 1,2,3-triazole in the side chain.

Ene-reaction of allyltrialkyltin, allylgermanes, allylsilanes and enoxysilanes with sulfur dioxide are well known.1 Our research is focused on application of silyl sulfinates 1 in the synthesis of functionalized sulfoxides 2 (Scheme 1). Application of silyl sulfinates 1 in organic chemistry has been demostrated in different fields, including their transformation into sulfones, sulfonamides, sulfonic esters,1 in total synthesis of polypropionate antibiotics2 and as silylation reagents for GC-MS quantative analysis.3 Traditional synthesis of sulfoxides 2 includes oxidation of sulfides and C-S bond formation with nucleophilic substitution.4 Various sulfinyl transfer agents have been used for C-S bond creation, but silyl sulfinates 1 provide a new approach towards sulfoxide 2 synthesis. In order to optimize the reaction conditions for sulfoxide 2 synthesis we investigated influence of solvent, temperature, organometallic reagent and Lewis acid additive on sulfoxide 2 yield. We have also diversified silyl moiety in sulfinate 1 structure, examining trimethylsilyl- (1a), terc-butyldimethylsilyl- (1b) and triisopropylsilyl sulfinate (1c) in order to increase the yields of sulfoxides 2. The optimal reaction conditions will be discussed and the scope of the method will be demonstrated on aryl-, alkyl-, allyl- and heterocyclic organometallic reagents.

An Efficient Synthesis of Methallyl Sulfoxides: Application of Sulfur Dioxide in C-S Bond Formation

The neodolastane diterpenoids comprise a group of 44 compounds including guanacastepenes, heptemerones, plicatilisins, radianspenes, 2, 15-epoxy-5, 13-dihydroxyneodolast-3-en-14-one and sphaerostanol. These fungal and marine natural products are characterized by a tricyclic neodolastane skeleton that consists of fused five-, seven- and six-membered rings. Their reported antibiotic activities against antibiotic-resistant bacteria together with strong antifungal and anticancer activities and their novel structures render these compounds interesting synthetic targets. The aim of this account is to summarise the progress in the isolation, characterisation and synthesis of these diterpenoids as well as to review their biogenetic origins and diverse biological activities since their discovery in 2000.

We were intrugued to explore the organocatalytic applications of furanose-derived thioureas 2 obtained form the branched beta-amino alcohols of general type 1.

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that are responsible for cleavage of extracellular matrix proteins. Because of their effect on both physiological and pathological processes, MMPs have become interesting targets for treatment of cancer. In addition, it is known that MMP-2 has the most important impact to tumor growth. Based on previous research, new series of aziridine and azetidine derivatives containing 1,4-disubstituted 1,2,3-triazole in the side chain as well as aziridine derivatives containing 1,5-disubstituted 1,2,3-triazole in the side chain were synthesized using transition metals catalyzed Huisgen 1,3-dipolar cycloaddition. MMP-2 inhibition studies of target compounds revealed some promising results among aziridine derivatives containing 1,4-disubstituted 1,2,3-triazole, while for other two series inhibition potency was not detected.

A novel method for the synthesis of C(2) and C(6) modified purine nucleoside analogues has been developed. The obtained triazolyl purine nucleosides were tested for their activity against Chikungunya virus, murine Norovirus, enterovirus 71 and yellow fever virus. Their cytotoxicity also was examined.