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Seyeon Kim 《Nucleosides, nucleotides & nucleic acids》2016,35(2):83-103
As antiviral nucleosides containing a fluorine atom at 2′-position are endowed with increased stabilization of glycosyl bond, it was of interest to investigate the influence of three fluorine atoms at 2′- and 5′-positions of apiosyl nucleoside phosphonate analogues. Various pyrimidine and purine 2′,5′,5′-trifluoro-3′-hydroxy-apiose nucleoside phosphonic acid analogues were synthesized from 1,3-dihydroxyacetone. Electrophilic fluorination of lactone was performed using N-fluorodibenzenesulfonimide. Difluorophosphonation was performed by direct displacement of triflate intermediate with diethyl(lithiodifluoromethyl) phosphonate to give the corresponding (α,α-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield nucleoside phosphonate analogues. Deprotection of diethyl phosphonates provided the final phosphonic acid sodium salts. The synthesized nucleoside analogues were subjected to antiviral screening against various viruses. 相似文献
3.
Zemlicka J 《Biochimica et biophysica acta》2002,1587(2-3):276-286
In order to overcome restrictions imposed by activation (phosphorylation) mechanism of antiviral and antitumor nucleoside analogues several prodrug approaches have been designed. Lipophilic pronucleotides are capable of intracellular delivery of monophosphates of nucleoside analogues, thus circumventing the limitations of enzymic phosphorylation. One of the successful approaches employs lipophilic amino acid ester (alanine) phenyl phosphoramidates as pronucleotides. This approach was applied to AIDS drugs such as AZT, d4T and related analogues but also to nonclassical nucleoside analogues based on allenic and methylenecyclopropane structure. Antiviral effects of the parent analogues were in many cases increased by conversion to phenyl phosphoralaninate (PPA) pronucleotides. Although cytotoxicity increase frequently accompanies antiviral effects of these pronucleotides, a favorable selectivity index can be obtained by manipulation of the parent structure as shown, e.g., for 2,6-diaminopurine methylenecyclopropane pronucleotide 15c. A lack of in vivo toxicity was demonstrated for 2-amino-6-methoxypurine methylenecyclopropane pronucleotide 15e in mice. The PPA pronucleotides can overcome deficiency of phosphorylating enzymes and offer favorable cross-resistance patterns when compared with other antiviral drugs. 相似文献
4.
Angell A McGuigan C Garcia Sevillano L Snoeck R Andrei G De Clercq E Balzarini J 《Bioorganic & medicinal chemistry letters》2004,14(10):2397-2399
Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family bearing a p-alkylphenyl side chain have been synthesised and tested for their antiviral activity against Varicella-Zoster virus (VZV). While the alkyl chain analogues were shown to retain full antiviral activity against VZV, these new analogues did not when compared to their furo parent nucleosides. 相似文献
5.
S N Mikha?lov 《Bioorganicheskaia khimiia》1992,18(8):1033-1066
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. 相似文献
6.
The enzymatic synthesis of antiviral agents. 总被引:2,自引:0,他引:2
The majority of potential antiviral agents which are currently undergoing clinical trials are inhibitors of the replication of nucleic acids. The most common class of these inhibitors are nucleoside analogues and the elucidation of synthetic routes to these compounds has been of interest for many years as many are anticancer agents. One synthetic development has been the application of bio-transformations to nucleoside syntheses. This topic has been reviewed recently (Shirae et al., 1991) but this review is not widely available. In the present review, the application of biotechnology to the synthesis of antiviral agents including those which are not nucleoside analogues will be discussed. Enzymatic syntheses of nucleosides can be simpler and quicker than syntheses carried out by chemical methods. The most useful enzymes are those found in catabolic pathways. Nucleoside phosphorylases and N-deoxyribosyltransferases have both been widely used for nucleoside synthesis catalysing the transfer of sugar residues from a donor nucleoside to a heterocyclic base. Enzymatic methods have also been applied to the resolution of racemic mixtures and adenosine deaminase is a convenient catalyst for the hydrolysis of amino groups on purines and purine analogues. Regioselective deprotection of nucleoside esters has been achieved with lipases and these enzymes have also been applied to the synthesis of esters of sugar-like alkaloids. The latter have potential as inhibitors of the replication of HIV. Esterases have also been used in combined chemical and enzymatic syntheses of organophosphorus antiviral agents. 相似文献
7.
Lian Jin Liu Jin Cheol Yoo Joon Hee Hong 《Nucleosides, nucleotides & nucleic acids》2013,32(2):150-164
An efficient route for synthesizing novel allylic and cyclopropanoid phosphonic acid nucleoside analogues is described. The condensation of the bromine derivatives 6 and 18 with nucleoside bases (A, U, T, C, G) under standard nucleophilic substitution and deprotection conditions, afforded the target phosphonic acid nucleoside analogues. These compounds were evaluated for their antiviral properties against various viruses. Cyclopropanoid phosphonic adenine nucleoside analogue 23 showed significant anti-HIV activity. 相似文献
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Eunae Kim 《Nucleosides, nucleotides & nucleic acids》2016,35(3):130-146
Racemic synthesis of novel 2′,5′,5′-trifluoro-apiose nucleoside phosphonic acid analogs were performed as potent antiviral agents. Phosphonation was performed by direct displacement of triflate intermediate with diethyl (lithiodifluoromethyl) phosphonate to give the corresponding (α,α-difluoroalkyl) phosphonate. Condensation successfully proceeded from a glycosyl donor with persilylated bases to yield the nucleoside phosphonate analogs. Deprotection of diethyl phosphonates provided the target nucleoside analogs. An antiviral evaluation of the synthesized compounds against various viruses such as HIV, HSV-1, HSV-2, and HCMV revealed that the pyrimidine analogues have significant anti-HCMV activity. 相似文献
10.
Gilles Gosselin Christophe Mathé Marie-Christine Bergogne Anne-Marie Aubertin Andre Kirn Jean-Pierre Sommadossi 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):611-617
Abstract Several L-enantiomers of nucleoside analogues were stereospecifically synthesized by a multi-step reaction from L-xylose and their antiviral properties were examined in vitro. Two of them, namely β-L-2′,3,′-dideoxycytidine (β-L-ddC) and its 5-fluoro derivative (β-L-FddC) were found to have potent anti-human immunodeficiency virus (HIV) and significant anti-hepatitis B virus (HBV) activities in cell cultures. 相似文献
11.
Zhang X Amer A Fan X Balzarini J Neyts J De Clercq E Prichard M Kern E Torrence PF 《Bioorganic chemistry》2007,35(3):221-232
To develop an understanding of the structure-activity relationships for the inhibition of orthopoxviruses by nucleoside analogues, a variety of novel chemical entities were synthesized. These included a series of pyrimidine 5-hypermodified acyclic nucleoside analogues based upon recently discovered new leads, and some previously unknown "double-headed" or "abbreviated" nucleosides. None of the synthetic products possessed significant activity against two representative orthopoxviruses; namely, vaccinia virus and cowpox virus. They were also devoid of significant activity against a battery of other DNA and RNA viruses. So far as the results with the orthopoxviruses and herpes viruses, the results may point to the necessity for nucleoside analogues 5'-phosphorylation for antiviral efficacy. 相似文献
12.
A series of phosphonate analogues of the antiviral cyclopropane nucleoside A-5021 were synthesized from (1S*, 7R*)-3,5-dioxa-4,4-diphenylbicyclo[5. 1.0]octane-l-methanol by a 10-step process. In contrast to the potent antiherpetic activity of A-5021, they were all devoid of antiviral activity. 相似文献
13.
Eunae Kim Lian Jin Liu Wonjae Lee Joon Hee Hong 《Nucleosides, nucleotides & nucleic acids》2013,32(2):85-96
Electronic parameters of 1′,3 ′-oxygen play significant roles in steering the conformation of nucleoside phosphonic acid analogues. To investigate the relationship of two oxygen atoms with antiviral enhancement, novel 1′,3 ′-dioxolane 5 ′-deoxyphosphonic acid purine analogues were synthesized via de novo acyclic stereoselective route from acrolein and glycolic acid. The synthesized nucleoside phosphonic acid analogues 14 and 19 were subjected to antiviral screening against several viruses, such as HIV-1, HSV-1, HSV-2, and HCMV. The guanine analogue 19 exhibits in vitro anti-HIV-1 activity similar to that of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) in MT-4 cells. 相似文献
14.
A. Van Aerschot Z. Ni J. Rozenski P. Claes E. De Clercq P. Herdewijn 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1791-1800
Abstract The synthesis and antiviral activity of a new series of acyclic nucleoside analogues containing a (2-hydroxyethoxy)ethyl moiety is discussed. 相似文献
15.
Novel 4'-cyclopropyl-5'-norcarbocyclic adenosine phosphonic acid analogues were designed and racemically synthesized from propionaldehyde 5 through a de novo acyclic stereoselective route using triple Grignard addition and ring-closing metathesis (RCM) as key reactions. To improve cellular permeability and enhance the anti-HIV activity of this phosphonic acid, SATE phosphonodiester nucleoside prodrug 23 was prepared. The synthesized adenosine phosphonic acids analogues 17, 18, 19, 21, and 23 were subjected to antiviral screening against HIV-1. Compound 23 exhibits enhanced anti-HIV activity than its parent nucleoside phosphonic acid 18. 相似文献
16.
Kim MJ 《Nucleosides, nucleotides & nucleic acids》2008,27(10):1097-1106
Based on the biological importance of conformationally restricted nucleoside analogues, we have efficiently synthesized 3,6-anhydro sugar moiety with 3-C-hydroxymethyl substituent from 1,2;5,6-di-O-isopropylidene-D-glucose and condensed 15 with silylated nucleobases to afford the bicyclic nucleoside with 3,6-anhydro skeleton as potential antiviral agent. 相似文献
17.
Boesen T Sejer Pedersen D Jensen J Munck MT Nielsen BM Petersen AB Henriksen U Dahl BM Dahl O 《Nucleosides, nucleotides & nucleic acids》2003,22(5-8):623-627
Preparation of the nucleoside analogues 1 and incorporation of 1, B = T, in deoxyribooligonucleotides by the phosphoramidite method is described. A two-step deprotection procedure was developed to reduce cleavage of the modified allylic unit. The binding properties of the modified oligonucleotides towards complementary DNA and RNA has been evaluated by Tm measurements showing a deltaTm of -2 to -6.5 degrees C per modification. An oligonucleotide with two modifications at the 3'-end showed considerable resistance towards cleavage by a 3'-exonuclease. No antiviral activity against HIV-1 or HSV-1 was found for 1, B = G or T, or for any of the trihydroxy derivatives 5. 相似文献
18.
Seyeon Kim 《Nucleosides, nucleotides & nucleic acids》2015,34(12):815-833
Novel 2′-deoxy-2′-β-fluoro-threose purine phosphonic acid analogues were designed and racemically synthesized from 2-propanone-1,3-diacetate. Condensation successfully proceeded from a glycosyl donor 9 under Vorbrüggen conditions. Cross-metathesis of vinyl analogues 13 and 23 with diethyl vinylphosphonate yielded the desired nucleoside phosphonate analogues 14 and 24, respectively. Ammonolysis and hydrolysis of phosphonates yielded the nucleoside phosphonic acid analogues 16, 19, 26, and 29. The synthesized nucleoside analogues were subjected to antiviral screening against human immunodeficiency virus (HIV)-1. Adenine analogue 18 exhibited weak in vitro activities against human immunodeficiency virus (HIV)-1. 相似文献
19.
A Brancale C McGuigan B Algain P Savy R Benhida J L Fourrey G Andrei R Snoeck E De Clercq J Balzarini 《Bioorganic & medicinal chemistry letters》2001,11(18):2507-2510
Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family are herein reported. The compounds retain full antiviral potency in comparison to the furo parent. 相似文献
20.
《Nucleosides, nucleotides & nucleic acids》2013,32(8):1187-1197
A series of phosphonate analogues of the antiviral cyclopropane nucleoside A-5021 were synthesized from (1S*, 7R*)-3,5-dioxa-4,4-diphenylbicyclo[5.1.0]octane-l-methanol by a 10-step process. In contrast to the potent antiherpetic activity of A-5021, they were all devoid of antiviral activity. 相似文献