Two novel bicyclo[6.1.0]nonyne (BCN) linker derivatives, which can be directly incorporated into oligonucleotide sequences during standard automated solid-phase synthesis, are reported. Stabilities of BCN-carbinol and two BCN-oligonucleotides evaluated under acidic conditions. In addition, derivatized BCN linkers (non-acidic acid treated) for strain-promoted alkyne-azide cycloaddition (SPAAC).

Triphenylphosphine selenide and its polymer-supported counterpart are found to be efficient selenium-transferring reagents for the conversion of H-phosphonate diesters phosphite triesters into corresponding phosphoroselenoate derivatives.

A practical and chromatography-free multikilogram synthesis of a 3-isoxazolol containing antifibrinolytic agent, AZD6564, has been developed in eight steps 7% overall yield starting from methyl 2-chloroisonicotinate. Highlights the are Negishi coupling an enzymatic resolution racemic ester.

The development of Zn2+-dependent dimethyl-dppz-PNA conjugates (PNAzymes) as efficient site-specific artificial ribonucleases enables rapid sequence-specific degradation clinically relevant RNA target sequences, but the significance RNA/PNAzyme sequence and structural demands for identification novel targets are not fully understood. In present study, we investigated influence variation in recognition arms complex on cleavage activity enzymes. base pairs closing 3-nucleotide bulge region...

Oligonucleotide (ON) conjugates are increasingly important tools for various molecular diagnostics, nanotechnological applications, and the development of nucleic acid-based therapies. Multiple labeling ONs can further equip ON-conjugates provide improved or additional tailored properties. Typically, preparation ON multiconjugates involves synthetic steps and/or manipulations in post-ON assembly. This report describes simplified methodology allowing multiple on a solid support is compatible...

Ethyl 6-chloro-5-cyano-2-methylnicotinate (4) was coupled with 4-piperidinecarboxylic acid (isonipecotic acid) in 81% yield to pyridine 10. An amide coupling between 10 and benzylsulfonamide (6) afforded AZD1283 (1) 79% using CDI as reagent. The synthesis has been developed scaled up 20 kg batches of 1, supporting preclinical clinical studies. Development work towards 2-chloropyridine 4 is included.

Abstract In this paper a short review is given of synthetic methods for the preparation nucleoside phosphorofluoridates, phosphorofluoridothioates and phosphorofluoridodithioates.

Iodine-promoted desulfurization of phosphorothioate and phosphorodithioate diesters in the presence triethylamine tris(hydrofluoride) (TAF) furnish a rapid quantitative formation corresponding phosphorofluoridates phosphorofluoridothioates; under reaction conditions phosphoroselenoate phosphoroselenothioate undergo deselenization affording phosphorofluoridate phosphorofluoridothioate diesters, respectively.

Elucidation of the mechanism formation two major impurities in synthetic route towards key intermediate ethyl 5-cyano-2-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate 1, led directly to development a with significant process improvements terms yield, purity, and operability. The overall yield increased from 15% 73% without need for extra purification steps, giving 6-chloro-5-cyano-2-methylnicotinate, 2, excess 80 kg support clinical development.

Retinitis pigmentosa (RP) is a form of retinal degeneration affecting young population with an unmet medical need. Photoreceptor has been associated increased guanosine 3′,5′-cyclic monophosphate (cGMP), which reaches toxic levels for photoreceptors. Therefore, inhibitory cGMP analogues attract interest RP treatments. Here we present the synthesis dithio-CN03, phosphorodithioate analogue cGMP, prepared using H-phosphonothioate route. Two crystal modifications were identified as trihydrate...

Using 31 P NMR spectroscopy as a tool, we investigated the condensation of H-phosphonoselenoate monoesters with hydroxy component in presence various coupling agents. On this basis, synthetic protocols that eliminate or significantly suppress side reactions which might occur during synthesis derivatives, have been developed. Absolute configuration produced dinucleoside H-phosphonoselenoates has determined by stereochemical correlation analysis.

Abstract In contribution to the pharmaceutical development of cyclic guanosine monophosphorothioate analogue cGMPSA as a potential active ingredient (API) for treatment inherited retinal degenerations (IRDs), its neutral form ( cGMPSA‐H ) and salts sodium ‐Na ), calcium ‐Ca ammonium ‐NH 4 triethylammonium ‐TEA tris(hydroxymethyl)aminomethane ‐Tris benethamine ‐Bnet benzathine ‐BZ were prepared. Their solid‐state properties studied with differential scanning calorimetry, thermogravimetric...

K. Misiura, W. J. Stec, M. Bollmark and Stawinski, Chem. Commun., 1999, 2115 DOI: 10.1039/A906659D

In this thesis, the chemistry of compounds containing P-Se bonds has been studied. As a new addition to class compounds, H-phosphonoselenoate monoesters, have introduced and two synthetic pathways for their preparation developed.The reactivity monoesters towards variety condensing agents From these, efficient conditions synthesis diesters developed. The produced subsequently used in oxidative transformations, which gave access corresponding P(V) e.g. dinucleoside phosphoroselenoates or...

In this paper a short account of our recent research concerning the development new synthetic methods and reagents for preparation nucleotides their analogues, is given.

The utility of a new type synthetic intermediates, H-phosphonoselenoate diesters, in the preparation potentially biologically important nucleotide analogues containing P-Se bond, was explored by converting dinucleoside H-phosphonoselenoates 1 into various phosphorus(V) derivatives under oxidative conditions.

2′-O-(N-(Aminoethyl)carbamoyl)methyl-modified 5-methyluridine (AECM-MeU) and 5-methylcytidine (AECM-MeC) phosphoramidites are reported for the first time prepared in multigram quantities. The syntheses of AECM-MeU AECM-MeC nucleosides designed larger scales (approx. 20 g up until phosphoramidite preparation steps) using low-cost reagents minimizing chromatographic purifications. Several steps were screened best conditions, focusing on most crucial such as N3 and/or 2′-OH alkylations, which...

Two approaches have been developed for the formation of phosphoramidates with nitrogen atom in bridging positions internucleotide linkage. One them makes use H-phosphonamidates as intermediates and other is based on oxidative coupling H-phosphonate monoesters or their analogues appropriate amines. Also, a new, convenient entry to nucleoside methylphosphonamidates, consisting an 3'-methylphosphinates 5'-aminonucleosides, was investigated. Finally, iodine promoted desulfurization...