A new RNA synthetic method with a 2'-O-(2-cyanoethoxymethyl) protecting group

A novel method for the synthesis of RNA oligomers with 2-cyanoethoxymethyl (CEM) as the 2'-hydroxyl protecting group has been developed. The new method allows the synthesis of oligoribonucleotides with an efficiency and final purity comparable to that obtained in DNA synthesis. [structure: see text]     

Synthesis of RNA using 2'-O-DTM protection

tert-Butyldithiomethyl (DTM), a novel hydroxyl protecting group, cleavable under reductive conditions, was developed and applied for the protection of 2'-OH during solid-phase RNA synthesis. This function is compatible with all standard protecting groups used in oligonucleotide synthesis, and allows for fast and high-yield synthesis of RNA. Oligonucleotides containing the 2'-O-DTM groups can be easily deprotected under the mildest possible aqueous and homogeneous conditions. The preserved 5'-O-DMTr function can be used for high-throughput cartridge RNA purification.     

Synthesis of 3-cyano-2-fluoropyridines

The synthesis of 3-cyano-2-fluoropyridines from readily available precursors was achieved via nucleophilic substitution of a leaving group in the 2-postion with KF or Bu₄NF in polar aprotic solvents such as DMF and DMSO. Ionic tetrahydrothiophenium fragment is the most effective leaving group, the methanesulfonyl moiety is a somewhat less effective, and Br- and Cl- are the least effective. Relatively mild conditions of the reaction between (2-pyridyl)-tetrahydrothiophenium salts and KF, as well as the convenience of one-step synthesis of these salts from 2(1H)-pyridinethiones, make these salts the compounds of choice for the preparation of ring-fluorinated pyridines.     

2-(4-Tolylsulfonyl)ethoxymethyl (TEM)-a new 2'-OH protecting group for solid-supported RNA synthesis

The 2-(4-tolylsulfonyl)ethoxymethyl (TEM) as a new 2'-OH protecting group is reported for solid-supported RNA synthesis using phosphoramidite chemistry. The usefulness of the 2'-O-TEM group is exemplified by the synthesis of 12 different oligo-RNAs of various sizes (14-38 nucleotides long). The stepwise coupling yield varied from 97-99% with an optimized coupling time of 120 s. The synthesis of all four pure phosphoramidite building blocks is also described. Two new reliable parameters, delta(C2')-delta(C3') and delta(H2')-delta(H3'), have been suggested for the characterization of isomeric 2'-O-TEM and 3'-O-TEM as well as other isomeric mono 2'/3'-protected ribonucleoside derivatives. The most striking feature of this strategy is that the crude RNA prepared using our 2'-O-TEM strategy is sufficiently pure (>90%) for molecular biology research without any additional purification step, thereby making oligo-RNAs easily available at a relatively low cost, saving both time and lab resources.     

A Convenient Synthesis of 2H-Pyran-2-one Derivatives

A simple procedure for the synthesis of 2H-pyran-2-ones 1 is described: selective Wittig olefination of keto aldehydes at the aldehyde group followed by a cyclization in acidic medium.     

Recent advances in [2+2+2] cycloaddition reactions

The [2+2+2] cycloaddition is an elegant, atom-efficient and group tolerant process for the synthesis of carbo- and heterocycles, mostly aromatic, involving the formation of several C-C bonds in a single step. Cyclotrimerisation is catalyzed by a variety of organometallic complexes, including more than 15 different metals. The aim of this tutorial review is to point out the most recent advances in this field and to encourage the use of this reaction enroute to complex molecules. After summarizing the most common catalysts and reaction conditions generally used, we survey the mechanistic features currently accepted for this reaction. Section 4 covers the scope of the different [2+2+2] cycloaddition versions starting with the cyclotrimerisation of three triple bonds, including nitriles, with especial emphasis on asymmetric reactions that create central, axial or planar chirality. Then, reactions that use double bonds are addressed. Finally, the most outstanding examples of natural products synthesis using [2+2+2] cycloadditions as a key step reported recently are shown.     

One-step synthesis of 2-indolylalkylamines

An efficient one-step synthesis of 2-indolylalkylamines was proposed. The synthesis involves the Fischer reaction of phenylhydrazine with cyclic imines containing a CH₂ group in the α-position or with amino ketones containing two CH₂ groups in the α-position with respect to the C=O group.     

Syntheses of 2-amino-4,6-dichloro-5-nitropyrimidine and 2-amino-4,5,6-trichloropyrimidine: an unusual aromatic substitution

2-Amino-4,6-dichloro-5-nitropyrimidine is an intermediate required for the preparation of nitropyrimidines as inactivators of the DNA repairing protein MGMT. When attempting its synthesis, 2-amino-4,5,6-trichloropyrimidine is obtained instead, via unusual aromatic substitution of the nitro group in 2-amino-4-hydroxy-5-nitropyrimidin-6-one by chloride. The synthesis, the reactivity of 4,5,6-trichloropyrimidine and the efficient preparation of 2-amino-4,6-dichloro-5-nitropyrimidine are presented.     

Synthesis of 2'-amino-LNA: a new strategy

In this paper we present revised and significantly improved synthetic routes to 2'-amino-LNA (locked nucleic acid). The optimal route is convergent with the synthesis of LNA monomers ("2'-oxy-LNA") via a common intermediate obtained by a mild deacetylation for the liberation of the 2'-hydroxy group to give compound 23 without the concomitant ring closure that affords the 2'-oxy-LNA skeleton. After inversion of the stereochemistry at C2' and triflate formation at the 2'-hydroxy group a new common intermediate 16 is obtained which gives easy access to a range of other analogues exemplified by the introduction of a sulfur nucleophile leading to the 2'-thio-LNA structure. After substitution of the triflate with azide a basic reduction affords the desired 2'-amino-LNA structure, i.e., compound 18. This new synthesis strategy towards 2'-amino-LNA improves the overall yield significantly and converges the syntheses of 2'-oxy-LNA and LNA analogues.     

酸促进2-乙烯基苯胺与重氮的[5+1]环化合成2-芳基喹啉

利用廉价易得的2-乙烯基苯胺与重氮化合物在三氟乙酸催化下发生[5+1]环化反应, 以中等至良好的产率合成了24种2-芳基喹啉衍生物. 该方法无需金属催化剂, 官能团兼容性好, 反应成本低, 不仅拓展了重氮化合物参与的新型有机反应, 同时也为2-芳基取代喹啉的合成提供了高效、 经济且简洁的新方法.     

Synthesis of new 2-amino-5-hydroxymethyl-2-thiazolines

A simple and convenient method is proposed for the synthesis of 2-amino-5-hydroxymethylthiazolines with various substituents in the amino group, which is based on hydrolysis of the corresponding 5-halomethyl derivatives of thiazoline in the presence of divalent lead oxide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 456–463, 2007.     

Solid-phase synthesis of 2-aminoquinazolinone derivatives with two- and three-point diversity

A versatile solid-phase method for the synthesis of various substituted 2-amino-4(3H)-quinazolinones with two- and three-point diversity is described. The synthesis commenced with the generation of polymer-bound S-methylisothiourea followed by N-acylation with different substituted o-nitrobenzoic acid. Finally, reduction of the nitro group triggered intramolecular cyclization via formation of guanidine to afford 2-amino-4(3H)-quinazolinone and its derivatives in high yields and purities.     

SN2 Reactions at Tertiary Carbon Centers in Epoxides

Described herein is a novel concept for S_N2 reactions at tertiary carbon centers in epoxides without activation of the leaving group. Quantum chemical calculations show why S_N2 reactions at tertiary carbon centers are proceeding in these systems. The reaction allows flexible synthesis of 1,3‐diol building blocks for natural product synthesis with excellent control of the relative and absolute configurations.     

Stereoselective synthesis of 2-amino-2-deoxysugars: N-alkyl-D-allosamines

Stereoselective synthesis of N-alkyl-D-allosamines, designed for the preparation of N-alkyl derivatives of allosamidin (a chitinase inhibitor), is achieved by a 'carbonyl group transfer' reaction followed by stereoselective reduction and this method represents the first example of N-alkyl-D-allosamines synthesized from a 2-oxosugar.     

Improved synthesis of porous C2N for CO2 conversion

Since the initial introduction of porous C₂N-h2D materials by the Baek group in 2015, these materials have exhibited highly promising applications in fields such as semiconductor devices, heterogeneous catalysis, gas storage and separation, biomedicine, and more. However, much of the existing research on C₂N materials has been based on theoretical calculations due to the challenges associated with their synthesis. In this study, an enhanced synthesis method for porous C₂N materials has been successfully developed, involving the innovative and nonexplosive synthesis of hexaaminobenzene trihydrochloride (HAB·3HCl) as a crucial intermediate, as well as a time-efficient synthesis of C₂N. Rigorous structural characterizations have been conducted, including solid-state NMR analysis, among others. The resultant C₂N material has been effectively employed to improve the efficiency of CO₂ conversion reactions. This straightforward protocol for synthesizing C₂N materials is poised to stimulate further exploration and application of this promising 2D material in the near future.     

Efficient one-pot synthesis of 1-alkoxy-2-arylaminoimidazolines from N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides and arylisothiocyanates

A new synthetic approach towards 1-alkoxy-2-aminoimidazolines that uses N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides as nucleophile reagents for the reaction with isothiocyanates is reported. Hence, the synthesis of 1-alkoxy-2-aminoimidazolines was performed in high yield with a one-pot procedure involving thiourea formation, nosyl group removal and spontaneous cyclization (42-77% overall yield).     

Synthese und Umlagerungsreaktionen von 2-(2-Amino-anilino)-2-imidazolin-Derivaten

The nitro-imidazolines V and VI are formed by addition reaction of ethylenediamine to the isothiocyanates III and IV. The nitro group is then converted by hydrogenation to the amino group, giving XI and XII, which can be acylated selectively to IX and X. By rearrangement in boiling xylene, the compounds XI and XII give the corresponding 2-(2-aminoethylamino)-benzimidazoles XIII and XIV. The benzoylated derivative IX gives the benzimidazole derivative XVIII by rearrangement and subsequent migration of the benzoyl group, while the benzylated derivative XVI gives the rearranged benzimidazole XXII. The benzimidazole structure of the rearranged products is proven by unambiguous synthesis of XIII, starting with 2-chlorobenzimidazole (VII) and mono-N-acetyl-ethylene-diamine to give compound VIII, from which XIII is obtained by hydrolysis.     

Enantioselective synthesis of axially chiral anilides through rhodium-catalyzed [2+2+2] cycloaddition of 1,6-diynes with trimethylsilylynamides

We have developed a rhodium-catalyzed enantioselective intermolecular [2+2+2] cycloaddition of 1,6-diynes with trimethylsilylynamides for the synthesis of axially chiral anilides. The axial chirality is constructed at the formation of benzene rings with high enantioselectivity (up to 98% ee). It should be noted that the present reaction employs the readily prepared trimethylsilylynamides starting from commercially available bis(trimethysilyl)acetylene and the trimethylsilyl group of the product anilides is expected to be utilized for further functionalization.     

Anion-templated assembly of [2]rotaxanes

Anion templation is used to develop a general method for rotaxane synthesis. The anion-templated synthesis of three new [2]rotaxanes containing positively charged pyridinium axles and neutral isophthalamide macrocyclic components is described. The incorporation of electron withdrawing substituents, such as the nitro group, into the 5-position of an isophthalamide bis-vinyl acyclic precursor results in a significant improvement in [2]rotaxane assembly yields. Rotaxane anion binding strengths are also enhanced whilst the rotaxane's unique interlocked binding domain ensures selectivity for chloride--the templating anion--is maintained.     

Oxidative Csp3-H functionalization of 2-methylazaarenes: A practical synthesis of 2-azaarenyl-benzimidazoles and benzothiazoles

Oxidative C_sp3-H functionalization of 2-methylazaarenes using I₂-DMSO in open flask has been described first time for the synthesis of 2-azaarenyl benzimidazoles and 2-azaarenyl benzothiazoles. Generally, methyl group of 2-methylazaarenes serves as a carbon nucleophile and in this work the methyl group served as electrophilic carbon (umpolung!) and condensed with o-Phenylenediamine and 2-aminothiophenol to furnish the corresponding benzimidazoles and benzothiazoles in high yields with good substrate scope and functional group tolerance.