Symmetrically and Unsymmetrically Bridged Methylenebis(allopurinols): Synthesis of Dimeric Potential Anti-Gout Drugs

Liquid-liquid phase transfer alkylation of 4-methoxy-pyrazolo[3,4-d]-pyrimidine (1a) with a dichloromethane/dibromomethane mixture (3:1, v/v) gave the regioisomeric methylenebis(heterocycles) 3a–5a. These were converted by dilute aqueous sodium hydroxide containing dimethylsulfoxide (DMSO) at concentrations between 0 and 60 vol-% into the methylenebis(allopurinols) 3b–5b by nucleophilic SNAr reactions at C(4). The effect of DMSO on the reaction kinetics was investigated

Immobilisierte Ribonucleoside - Ihre Synthese und Bioaffinität

A novel method for the immobilization of ribonucleosides to polysaccharides, namely to agarose, is presented, and the immobilized nucleosides are used for the purification of nucleoside-converting enzymes, such as adenosine deaminase, guanase OMP-decarboxylase and xanthine oxidase

Specific DNA duplex formation at an artificial lipid bilayer: fluorescence microscopy after Sybr Green I staining

The article describes the immobilization of different probe oligonucleotides (4, 7, 10) carrying each a racemic mixture of 2,3-bis(hexadecyloxy)propan-1-ol (1a) at the 5’-terminus on a stable artificial lipid bilayer composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). The bilayer separates two compartments (cis/trans channel) of an optical transparent microfluidic sample carrier with perfusion capabilities. Injection of unlabeled target DNA sequences (6, 8, or 9), differing in sequence and length, leads in the case of complementarity to the formation of stable DNA duplexes at the bilayer surface. This could be verified by Sybr Green I double strand staining, followed by incubation periods and thorough perfusions, and was visualized by single molecule fluorescence spectroscopy and microscopy. The different bilayer-immobilized complexes consisting of various DNA duplexes and the fluorescent dye were studied with respect to the kinetics of their formation as well as to their stability against perfusion

Terminal lipophilization of a unique DNA dodecamer by various nucleolipid headgroups: Their incorporation into artificial lipid bilayers and hydrodynamic properties

A series of six cyanine-5-labeled oligonucleotides (LONs 10–15), each terminally lipophilized with different nucleolipid head groups, were synthesized using the recently prepared phosphoramidites 4b–9b. The insertion of the LONs within an artificial lipid bilayer, composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE), was studied by single molecule fluorescence spectroscopy and microscopy with the help of an optically transparent microfluidic sample carrier with perfusion capabilities. The incorporation of the lipo-oligonucleotides into the bilayer was studied with respect to efficiency (maximal bilayer brightness) as well as stability against perfusion (final stable bilayer brightness). Attempts to correlate these parameters with the log P values of the corresponding nucleolipid head groups failed, a result which clearly demonstrates that not only the lipophilicity but mainly the chemical structure and topology of the head group is of decisive importance for the optimal interaction of a lipo-oligonucleotide with an artificial lipid bilayer. Moreover, fluorescence half-live and diffusion time values were measured to determine the diffusion coefficients of the lipo-oligonucleotides

Electrophilic Substitution at C(7) of a Protected 7-Deaza-2’-deoxyguanosine – The 2’-Deoxyribonucleoside Parent Analogue of Queuosine #

In this manuscript we report on the regioselective electrophilic substitution at C(7) of 7-[2-deoxy-3,5-bis-O-(2-methylpropanoyl)-ß-D-erythro-pentofuranosyl]-2-(formylamino)-4-methoxy-7H-pyrrolo[2,3-d]pyrimidine (2) – a protected precursor of 7-deaza-2’-deoxyguanosine - using N,N-dimethyl-methyleniminium iodide (Eschenmoser’s salt) yielding the Mannich compound 4

Towards the Synthesis of Inosine Building Blocks for the Preparation of Oligonucleotides with Hydrophobic Alkyl Chains Between the Nucleotide Units

The scientific objective of the research reported in this manuscript was the synthesis of novel phosphoramidite building blocks for the preparation of lipophilic oligonucleotides. Reaction of inosine (4) with 4-oxopentyl-4-methylbenzoate (2c) in the presence of triethyl orthoformate and 4M HCl in 1,4-dioxane gave a diastereoisomeric mixture of the ketals 5. Subsequent 4,4’-dimethoxytritylation at the 5’-hydroxyl afforded (R)-6 + (S)-6 which could be separated chromatographically. Detoluoylation gave compounds (R)-7 and (S)-7. Phosphitylation of a diastereoisomeric mixture of 7 led to a mixture of four diastereoisomers of the corresponding 2-cyanoethylphosphoramidites 8

Spontane Akkumulation lipophiler Oligonucleotide an der flüssig/flüssig-Phasengrenze

Assembly of lipo-oligonucleotide at a phase boundary of water and n-decane

Nomenclature of logP Values of Nucleosides and Nucleolipids

The paper describes a novel nomenclature system for the denomination of nucleosides and nucleolipids and presents the logP values of the compounds

Perspectives in Nucleoside and Nucleic Acid Chemistry

The chemistry of nucleosides and nucleic acids is a rapidly developing field. Many of the most important recent advances in medicinal chemistry have occured in this field with the development of novel nucleosideand nucleotide-based antiviral and antitumor drugs.[...