Borane-amine complexes--versatile reagents in the chemistry of nucleic acids and their analogs

A new method for synthesis of N-alkylated nucleosides was developed. Exceptionally mild and selective conversion of N-acyl to the corresponding N-alkyl nucleosides was achieved by reduction with borane-amine complexes. The borane-amine complexes were also used as efficient scavengers of a 4,4'-dimethoxytrityl (DMT) cation. Neutralization of the cation eliminated the boranophosphate group degradation during acidic DMT deprotection and allowed milder acidic conditions for the deprotection.     

Synthesis of 6-O-cyclopyrimidine nucleosides and their physicochemical properties

Treatment of 5-iodopyrimidine nucleosides with sodium methoxide afforded 6:2'-, 6:5'- and novel 6:3'-O-cyclopyrimidine nucleosides. The rates of cyclization and ring-opening, and the UV-, CD-, mass- and 13C-NMR spectra of the cyclonucleosides were compared with regard to their isomers.     

Quantitative changes in the content of nucleic acid bases and their derivatives in a culture ofPenicillium sizowi

Acid-soluble (“free”) nucleotides, nucleosides and bases were analyzed in the mycelium and in the culture filtrate of the fungusPenicillium sizowi, using micro-thin-layer chromatography on alumina and densitometry of the zones of the individual components. It was found that the levels of the various components underwent complicated changes, the corresponding curves exhibiting from one to three maxima which occur at different periods of cultivation. It was observed that a substantial amount of nucleotides, nucleosides and bases occurs in the medium as early as at the beginning of the exponential phase of growth. An attempt was made to elucidate some peculiarities of the nucleotide pool ofPenicillium species, using enzymes responsible for the individual transformations of nucleotides, nucleosides and bases.     

Synthesis of S-adenosyl-L-homocysteine hydrolase inhibitors and their biological activities.

Several nucleosides have been prepared as a possible inhibitor of human S-adenosyl-L-homocysteine (SAH) hydrolase for the development of anti-viral agents. Recently, SAH hydrolase has been considered as an attractive target for parasite chemotherapy for malaria. We report synthesis of several nucleosides including carbocyclic nucleosides and their inhibitory activities against recombinant malaria and human SAH hydrolases.     

Achievements and prospects of the directed search for antiviral agents in the nucleoside series and their derivatives]

Recent advances of antiviral drug design among nucleosides and their derivatives have been summarized. The first chapter deals with the history of nucleic acids components and further developments in this area. Next part discusses the mechanism of action of biologically active nucleosides: 2',3'-dideoxynucleosides, acyclic analogues, phosphonate derivatives and nucleoside antibiotics. The third chapter describes planning of complicated synthesis of nucleoside analogues from branched-chain sugars and stereo-specific formation of glycosidic bond upon synthesis of ribonucleoside and 2'-deoxyribonucleoside. The last part outlines further perspectives, i. e. preparation of antiviral compounds and use of nucleoside analogues in oligonucleotide synthesis.     

Analysis of natural nucleosides and their derivatives by thin-layer chromatography

Recently published data on the separation and quantification of natural nucleosides and some of their derivatives by thin-layer chromatography on silica gel have been summarized. The use of more than 20 mobile systems for the separation of more than 52 nucleosides and derivatives was discussed; in a few cases, the conditions for their densitometry quantitative analysis after TLC separation were considered. The works performed at GosNIIgenetika on the determination of inosine, thymidine, and acadesine with domestic Sorbfil plates were reviewed in detail.     

Pyrimidinethione nucleosides and their deaza analogues

The methods of preparation, structure, chemical properties and synthetic potentiality of pyrimidinethione nucleosides and their deaza analogues are reported.     

Solubilization of murine melanoma xylosyltransferase and galactosyltransferase activities and their inactivation by dialdehyde nucleosides

The enzymes involved in the initial steps in the biosynthesis of glycosaminoglycans were examined in the murine B16 melanoma. Approximately 60% of the melanoma xylosyltransferase activity and nearly all of the galactosyltransferase activity were membrane-bound; these enzymatic activities were solubilized by treatment with Nonidet P-40 and potassium chloride, and the Michaelis constants for the substrates and acceptor molecules were determined and found to be comparable to those reported for these enzymes from the chick embryo and a rat chondrosarcoma. Dialdehyde nucleosides, which have been reported to alter the activity of several enzymes involved in nucleic acid synthesis, inhibited both xylosyltransferase and galactosyltransferase activities, with galactosyltransferase being considerably less sensitive than xylosyltransferase. The inhibition of xylosyltransferase by dialdehyde nucleosides was irreversible, with no apparent specificity for the base moiety of the dialdehyde nucleosides.     

N4-hydroxycytosine dioxolane nucleosides and their activity against hepatitis B virus

Novel racemic, D- and L-beta-dioxolane N4-hydroxycytosine nucleosides have been synthesized and evaluated for their activity against hepatitis B virus. None of the synthesized nucleosides demonstrated selective anti-HBV activity.     

Selective syntheses of 6-substituted pyrimidine nucleosides and their interactions with uridine phosphorylase

Several 6-substituted pyrimidine nucleosides have been prepared by condensation of an N(3)-benzyl or C(4)-methylthio pyrimidine with the appropriately blocked sugar, followed by the use of mild conditions at room temperature for removal of blocking groups. The substrate properties of these nucleosides, which are in the fixed syn conformation, have been examined in the uridine phosphorylase system.     

Elongation of oligonucleotides in the 3'-direction with activated mononucleotides and their analogs using RNA ligase.

P1-Adenosine 5'-P2-2',3'-ethoxymethylidene nucleosides [A(5')ppN(Em)] from four common nucleosides have been prepared and used for single addition of nucleotides to elongate oligonucleotide chains in the 3'-direction in RNA ligase reaction. U-U-C, T-U-C and A-C-C were used as acceptors. Structural dependence in these acceptors was found to be smaller compared to joining reactions between oligonucleotides. Adenosine analogs including 8-bromo-, 2'-fluoro-, 2'-azido-, 8,2'-O-cyclo-, 8,2'-S-cyclo-adenosine, arabinosyladenine and 2'-deoxyadenosine were added to the 3'-end of A-C-C by adenylation chemically followed by joining with RNA ligase. Symmetrical 5'-pyrophosphates of 8-bromo-, 2'-fluoro- and 2'-azido-adenosine were not recognized as donor substrates.     

New synthetic strategies for acyclic and cyclic pyrimidinethione nucleosides and their analogues

Pyrimidinethione nucleosides are effective compounds and have significant and pivotal effects in several fields. New synthetic strategies for many pyrimidinethione nucleosides including acyclic and cyclic derivatives have been reported.     

Use of automated chromatography on the amino acid analyzer with lithium citrate buffers to separate nucleic acid bases, nucleosides, nucleotides and their precursors

A simple and sensitive method has been developed to separate nucleic acid bases, nucleosides, nucleotides and their precursors by automated chromatography using the amino acid analyzer with lithium citrate buffers. The method is sensitive to a concentration of 5 nmol, linear in the range of 5--100 nmol, and resolves almost all the bases, nucleosides, nucleotides and their precursors of physiologic importance.     

Temperature dependence of the electronic absorption spectra of polynucleotides and their components]

The temperature dependence of UV-absorption spectra of solutions nucleic bases, nucleosides, nucleotides and metilated bases, uncapable of tautomerization has been studied. The nature of such dependence, its connection with hypochromic effect is discussed. It is shown that for some methods of investigating polynucleotides it is necessary to take into account the temperature changes spectra of monomers.     

Preparation of 8-Chloropurine Nucleosides Through the Reaction Between their C-8 Lithiated Species and p-Toluenesulfonyl Chloride

Abstract

Chlorination of purine nucleosides protected with tert-butyldimethylsilyl (TBDMS) group was examined by the reaction of the C-8 lithiated species, generated by LDA, with p-toluenesulfonyl chloride as an electrophile. This provides a new method for the preparation of 8-chloropurine nucleosides.     

Formation of l-Butyl-5-hydroxy-methylpyrrole-2-carboxaldehyde in the Maillard Reaction between Lactose and n-Butylamine

A new mutant Shm^r-001-1 has been isolated by treating showdomycin-resistant mutant Shm^r-001 cells with N-methyl-N′-nitro-N-nitrosoguanidine. This mutant was resistant to high level of showdomycin, and took up practically no showdomycin and little pyrimidine nucleosides, and it showed different ability to take up purine nucleosides. Strains Shm^r-001–1, Shm^r-001, and K–12 (wild type) were compared: in susceptibility to showdomycin, in ability to take up the antibiotic and various nucleosides, on effects of other nucleosides on entry of particular nucleosides, and on kinetics of the entry of nucleosides and showdomycin. From these experiments, at least three different nucleoside transport systems were observed in Escherichia coli K–12 cells: the first system was common to adenine nucleosides, pyrimidine nucleosides, and showdomycin; the second system was common to adenine nucleosides, guanine nucleosides, inosine, pyrimidine nucleosides, and showdomycin; and the third system was common to adenine nucleosides, guanine nucleosides, and inosine. The first system was not observable in Shm^r-001 cells. In Shm^r-001–1 cells both the first and the second systems were no longer detectable but the third system was found to be active.     

Rearrangement reactions of guanosine cyclonucleosides and their analogs

Under acid-catalyzed transglycosylation conditions 5',8-cyclo-8-oxoguanine nucleosides undergo a ring-opening reaction to 8-oxoguanine derivatives, instead of the 7-9 isomerization.     

Conformational studies of two isomeric ring-expanded purine nucleosides and their 5'-mono- and -diphosphate derivatives

The nucleosides Ia and IIa exist in syn and anti conformations, respectively, both in solid state and solution. Compound Ia undergoes significant conformational change, accompanied by increased population of the anti conformer, upon conversion to the corresponding 5'-mono- and- diphosphate derivatives, whereas conformation of IIa remains reasonably constant between nucleoside and nucleotides. While Ia possessed the C2'-endo-C3'-exo geometry, IIa had the opposite C2'-exo-C3'-endo conformation. The C5' of the two nucleosides bore axial and equatorial conformations, respectively.     

3'-deoxyribofuranose derivatives of 1-deaza and 3-deaza-adenosine and their activity as adenosine deaminase inhibitors

2,6-Dichloro-1-deazapurine and 2,6-dichloro-3-deazapurine were coupled with 1,2-O-diacetyl-5-O-benzoyl-3-deoxy-beta-D-ribofuranose. Deprotection of the obtained compounds and reaction with liquid ammonia gave the desired 2-chloroadenine nucleosides, which were dechlorinated to afford the corresponding 1-deaza and 3-deazaadenosine derivatives. Biological studies performed on ADA from calf intestine showed that these new nucleosides are inhibitors of the enzyme.