Thermal 7-9 transglycosylation of purine nucleosides and their analogues

A novel thermal 7 in equilibrium 9 transglycosylation reaction was studied in the series of fully acetylated purine ribonucleosides and their 2-acetoxyethoxymethyl analogues. Ratio 7- to 9-isomers in the resultant mixtures was determined by the proton magnetic resonance spectroscopy.     

Synthesis of (Z)-(2,3-bis-hydroxymethyl)methylenecyclopropane analogues of purine nucleosides

Synthesis of (Z)-(2,3-bis-hydroxymethyl)methylenecyclopropane analogues of nucleosides adenosine 10a, 10b, 10c and 17 is described. Epimerization of Feist's acid (11) using acetic anhydride gave cyclic anhydride 12 which was reduced in situ to give diol 13. Acetylation (compound 14) followed by addition of bromine led to dibromo derivative 15. Alkylation-elimination of adenine with 15 afforded, after deacetylation, analogue 10a. Similar treatment of 2-amino-6-chloropurine and 2,6-diaminopurine led to diacetates 16 and 18. Deprotection then gave compounds 17 and 10c. Hydrolysis of 17 furnished guanine analogue 10b. Compounds 10a, 10b or 10c were inactive against HCMV, HSV-1, HSV-2, EBV VZV and HBV. Analogues 10a and 10b were also assayed for anti-HIV activity. Compound 10a was effective in HIV-1/MT-2 culture with EC50/CC50 33/> 100 microM but 10b was inactive. Analogue 10a was not a substrate for adenosine deaminase.     

Synthesis, antiviral, and antitumor activity of 2-substituted purine methylenecyclopropane analogues of nucleosides

The Z- and E-2-fluoro- and 2-chloropurine methylenecyclopropanes 9a,b and 10a,b as well as enantiomeric Z-isoguanine methylenecyclopropanes 11a,b and their phenyl phosphoralaninate pronucleotides 11c,d were synthesized and their antiviral activity against several viruses was evaluated. Fluoro analogues 9a and 10a were active against human cytomegalovirus but they were cytotoxic at approximately the same concentrations. Chloro derivatives 9b and 10b were non-cytotoxic and effective against Epstein-Barr virus in Daudi cells. Isoguanine analogues 11a-d lacked antiviral activity but pronucleotides 11c,d were substrates for porcine liver esterase. From the group of 9a,b and 10a,b, the fluoro analogues 9a and 10a exhibited antitumor activity but only the Z-isomer 9a had a selective effect.     

Synthesis of 2'-amino-LNA purine nucleosides

The first reported synthesis of 2'-amino-LNA purine nucleosides via a transnucleosidation is accomplished enabling the preparation of oligonucleotides incorporating 2'-amino-LNA with all four natural bases.     

An improved microbial synthesis of purine nucleosides

E. coliBL21 synthesized purine nucleosides from pyrimidine ones. A 94% yield of adenosine from uridine was reached within 1 h.     

Gold complexes of purine and pyrimidine nucleosides

The reactions of chloroauric acid (HAuCl₄) with inosine=ino, guanosine=guo, triacetylinosine=trino, triacetylguanosine=trguo, and cytidine=cyd were studied. Complexes of Au(III) and Au(I) with these nucleosides have been isolated from reactions at different pH values in aqueous and in methanolic solutions. The Au(I) complexes were obtained by reducing Au(III) with 1-ascorbic acid in aqueous solutions. All the isolated complexes were characterized by elemental analyses, conductivity measurements, IR, ¹H nmr, and esr spectra. The Au(III) complexes correspond to the general formulae [Au(nucl)₂Cl₂] Cl, Au(nucl)Cl₃, and Au(nucl-H⁺)Cl₂, while the Au(I) complexes are of the Au(nucl)₂Cl type, where nucl represents the above nucleosides. In the complex with the composition [AucydCl₂]₂ that was isolated from aqueous solutions, the Au atom is believed to be in the (II) oxidation state.Possible structures for all the isolated complexes based on the experimental data are proposed and discussed.     

4'-C-methyl-beta-D-ribofuranosyl purine and pyrimidine nucleosides revisited

In order to evaluate their antiviral properties, a series of 4'-C-methyl-beta-D-ribofuranosyl purine and pyrimidine nucleosides has been prepared. Unfortunately, none of these 4'-branched nucleosides showed any antiviral activity or cytotoxcity when tested against HIV, HBV, and Yellow Fever virus.     

Phenylacetyl group as enzyme-cleavable aminoprotection of purine nucleosides

N⁶-Phenylacetyl-2′-deoxyadenosine and N²-Phenylacetyl-2′-deoxyguanosine are readily deprotected in reactions catalyzed by free and immobilized penicillin amidase at pH 7.8 and 25°C.     

Mediated transport of nucleosides by human erythrocytes specificity toward purine nucleosides as permeants

Transport of uridine and thymidine across the plasma membrane of human eruthrocytes is mediated by a facilitated diffusion mechanism with broad specificity toward the base portion and narrow specificity toward the sugar portion of pyrimidine nucleosides. Specificity of this mechanism was further investigated by measuring efflux of radioactivity when erythrocytes containing radioactive uridine were incubated in medium containing purine nucleosides. Adenosine, guanosine, inosine, and arabinosyladenine accelerated uridine efflux and were therefore considered substrates for the transport mechanism. 6-Thioinosine, 6-thioguanosine, and several S-substituted 6-thiopurine ribonucleosides inhibited efflux of radioactive uridine. Adenine nucleosides with sugar moieties other than ribose or arabinose inhibited or had no effect on uridine efflux.     

具有分解嘌呤核苷能力的益生菌菌株筛选

在不同的肠道菌群及奶制品样品中筛选益生菌菌株,对其耐酸和耐胆盐能力、分解嘌呤核苷能力进行评价,为后续研发治疗高尿酸血症益生菌制剂提供依据。

采集内蒙古地区及巴马长寿村的健康婴儿肠道菌群或奶豆腐、奶疙瘩制品,通过选择性培养基划线培养、镜检及16S rDNA测序的方式筛选益生菌菌株。通过耐酸、耐胆盐试验,模拟胃液和模拟肠液筛选出对胃肠道环境耐受能力强的菌株并通过电镜观察其形态。再进一步通过分解嘌呤核苷能力检测确定分解能力最优的菌株。

在8个样本中筛选出23株益生菌,对其胃肠耐受能力进行检测后发现筛选出了8株耐受能力较强的益生菌菌株,分别为鼠李糖乳酪杆菌RH01103,罗伊氏粘液乳杆菌HCS02-001,植物乳植杆菌RH03010,动物双歧杆菌乳亚种RH04020,发酵粘液乳杆菌RH08050,副干酪乳酪杆菌HCS17-040,乳酸片球菌RH27102和戊糖片球菌RH34011。通过对分解嘌呤核苷能力检测,发现与未接种益生菌的空白对照组相比,罗伊氏粘液乳杆菌HCS02-001和副干酪乳酪杆菌HCS17-040对肌苷和鸟苷的分解能力最显著（P = 0.0002, P＜0.0001）。

8个样本筛选出的23株益生菌中罗伊氏乳杆菌HCS02-001和副干酪乳杆菌HCS17-040的胃肠耐受能力最强,分解嘌呤核苷效率最高。

     

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.     

Synthesis and biological activities of 2-functionalized purine nucleosides

Novel purine nucleosides functionalized at the 2-position have been prepared using new applications of synthetic methodology. The target molecules were designed as potential inhibitors (as their monophosphates) of the enzyme, inosine monophosphate dehydrogenase (IMPDH), and representative inhibition data are presented. Antiviral data of the compounds are discussed.     

1,2-disubstituted cyclohexane carbocyclic analogues of nucleosides

Several compounds of a new series of cyclohexane-based 1,2-disubstituted carbonucleoside analogues, were synthesized. The adenine and uridine derivatives, were prepared by construction of the heterocyclic base on the primary amino group of 2-aminocyclohexylmethanol, and the thymine derivative by condensation of 2-hydroxycyclohexylmethanol with thymine using the Mitsunobu reaction.