Synthesis and Biological Evaluation of some Acyclic Nucleoside Cyclic Phosphoramidate Derivatives

Abstract

The acyclic nucleosides 2 were treated with 2-chloro-3-methyl-1-oxa-3-aza-2-phosphacyclopentane (3) in the presence of diisopropylethylamine to give the corresponding phosphoramidite derivatives (4). The phosphoramidite intermediates (4) were oxidized with m-chloroperbenzoic acid to the phosphoramidate derivatives (5). Treatment of 5a,b with ZnBr₂ in CH₃NO₂ gave the corresponding acyclic nucleoside cyclic phosphoramidates (6a,b). Attempts to desilylation of 5c by tetrabutylammonium fluoride (TBAF) resulted in opening of the phosphoramidate ring. The newly synthesized compounds were evaluated for antiviral and antitumor cell activity.     

Synthesis of Some New Nucleoside Analogues as Potential Antiviral Agents

Abstract

A novel series of pyrimidine nucleoside analogues was synthesized. 2,3-Dideoxy-2,3-anhydro-β-D-lyxofuranose was opened by sodium azide to give the corresponding azido compound, which was reduced by lithium aluminium hydride to lead to 2,3-dideoxy-2,3-epimino-β-D-ribofuranose. Pyrimidine bases were glycosylated with this synthon to give potential antiviral molecules: 1-(2,3-dideoxy-2,3-epimino-β-D-ribofuranosyl)pyrimidines.     

Synthesis and Biological Activity of Some Nucleoside Analogs of Hydroquinoline-3-Carbonitrile

Hydroquinoline acyclonucleosides 2, 4, 6a,b, 8a,b, 9a,b, and their corresponding N-alkyl derivatives (10–12) were obtained by the reaction of 1a,b with acetoxybutylbromide, (2-acetoxyethoxy)methyl bromide, 3-chloropropanol, 1,3-dichloro-2-propanol, epichlorohydrin, propargyl/allyl bromides in the presence of K₂CO₃ in dry dimethylformamide (DMF). In a similar manner, reaction of 1a,b with glycosyl/galactosyl and lactosyl bromide afforded the corresponding N-nucloside derivatives 13a,b, 15a,b, and 17, respectively. Deacetylation of the N-nucleosides derivatives in the presence of Et₃N/MeOH and few drops of water gave the deprotected derivatives 3, 5, 7a,b, 14a,b, 16a,b, and 18 in good yields, respectively. All the newly synthesized compounds are elucidated by infrared, ¹H, ¹³C NMR and elemental analyses. Some of these compounds were screened for antimicrobial activities.     

Synthesis in Nucleoside Antibiotics

Both ribofuranoside (3) and ribopyranoside (5) of 4-amino-5-cyano-6-methy lmercaptopyr-rolo[2,3-d]pyrimidine (analogs of toyocamycin) have been synthesized for the first time by the fusion procedure using bis-(p-nitrophenyl) hydrogen phosphate as catalyst. Evidence for the β-configuration has been provided by analyzing the NMR spectra and ORD curves. The tumor-inhibitory activity of 3 against EhrIich ascites carcinoma in mice has also been examined.     

Synthesis of Some Fully 3′ and 4′-C-Branched-Chain Sugar Nucleoside Analogues

Abstract

The synthesis of some new 3′-azido-3′-C-substituted pyrimidine nucleoside analogues is described. The key step is the geminal disubstitution of an appropriated ketone carbohydrate, via the regioselective ring opening of the corresponding tosyl-epoxide derivative.     

Synthesis of Triazole Nucleoside Derivatives

Abstract

5′-O-Mesyl-2′,3′-O-isopropylidene ribonucleosides (4 and 12) were converted to their 5′-substituted nucleosides in good yields by reacted with NaN₃ or KI. 2′,3′-O-Isopropylidene ribonucleosides (3 and 11) were prepared in good yields from ribonucleosides 1 and 2 with a reaction mixture of acetone and triethyl orthoformate instead of using acetone diethyl acetal. Compound 1 or 2 was treated with 2-acetoxyisobutyryl halide (Cl or Br) to give 1-[2-O-acetyl-3-halo-3-deoxy-5-O-(2,5,5-trimethyl-1,3-dioxolan-4-on-2-yl)-β-D-xylofuranosyl]-1,2,4-triazole-3-carboxamide (19, 22, and 23) in high yields. Instead of using 2-acetoxyisobutyryl bromide, the mixture of 2-acetoxyisobutyryl chloride and NaBr was employed in the synthesis of 22 and 23. Treatment of 19 with an activated Zn/Cu couple and deprotection gave 2′,3′-anhydro nucleoside (21), and treatment of 22 and 23 with an activated Zn/Cu couple and a little of HOAc and deprotection gave corresponding 2′,3′-unsaturated triazole nucleosides (24 and 25), respectively. The biological activity of the compounds (7 ～ 10, 15 ～ 18, and 24) was examined in human liver cancer cells (A-549), lung cancer cells (BEL-7402), and Flu-A cells.

Synthesis of Triazole Nucleoside Derivatives

All authors

Zicheng Li, Shuhua Chen, Ning Jiang & Gang Cui

https://doi.org/10.1081/NCN-120022032

Published online:

07 February 2007

Compound 1.     

8.

The Synthesis and Antiviral Activity of Some New S-Adenosyl-L-homocysteine Derivatives and Their Nucleoside Precursors     

Pawel Serafinowski  Erwin Dorland  Jan Balzarini  Erik De Clercq 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):545-547

Abstract

S-Adenosyl-L-homocysteine (SAH) and some of its analogues are potent inhibitors of transmethylation reactions catalysed by S-adenosyl methionine dependent methyltransferases.¹     

9.

The Synthesis of 5-Substituted-2, 4-dimethoxypyrimidines and Some Related Nucleoside Analogues     

R. F. Whale  P. L. Coe  R. T. Walker 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1425-1442

Abstract

The reaction of 5-formyl-2,4-dimethoxypyrimidine with active methylene compounds in the Knoevenagel reaction and the subsequent nucleoside formation reactions of some of the products was investigated. A new synthesis of (E)-5-(2-bromovinyl)uracil and an improved synthesis of 5-formyl-2′,3′-isopropylidene uridine are reported.     

10.

Synthesis of Novel Polycyclic Nucleoside Analogs     

Norbert Bischofberger  Mark D. Matteucci 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):859-862

Abstract

We have synthesized polycyclic nucleoside derivatives by a novel, one pot procedure by reacting 4-0-TPS-pyrimidine nucleosides with aromatic diamines. The reaction is limited in scope but provides easy access to certain previously unknown heterocyclic ring systems.₂ 4-0-Triisopro- pylphenylsulfonyl-pyrimidine nucleosides were reacted with aromatic diamines leading to fused, polycyclic ring systems: o-phenylenediamine yielded the pyrimido[1,6-a]benzimidazole, 2.3- diaminonaphthalene gave the naphth[2′,3′:4,5]imidam [1.2-flpyrimidine and 1.8-diaminonaph- thalene led to the pyrimido[l,6-a]perimidine ring system. The reaction is unique because two connected nucleophilic centers react with the pyrimidine nucleoside to form an extended ring system. However, reactions of pyrimidine nucleosides with electrophiles are well known. E.g., reaction of cytidine and adenosine with bromoacetaldehyde yields ethenocytidine and ethenoadenosine) and on reaction of cytidine with 1′-methylthiaminium salts dipyrimido[1,6-a:4′,5′-d]pyrimidine derivatives are obtained.₄ Other polycyclic bases have been made from cytidine and adenosine by photochemical reactions₅.     

11.

Synthesis of a Novel Carbocyclic Nucleoside     

George A. Kraus  Todd Begey  Xuemei Wang 《Nucleosides, nucleotides & nucleic acids》2013,32(10-11):1961-1965

Abstract

Carbocyclic nucleoside 1 was prepared from carbomethoxy cyclopentanone in eight steps.     

12.

Synthesis of New Thiazolidinone Nucleoside Analogues     

J. C. Graciet  P. Faury  M. Camplo  A. S. Charvet  N. Mourier  C. Trabaud 《Nucleosides, nucleotides & nucleic acids》2013,32(6):1379-1392

Abstract

The synthesis of new thiazolididone nucleoside analogues is described. Among the different proposed synthetic pathways, the condensation of various nucleic bases using TMSOTf and Et₃N as coupling reagents on a key sulfoxide thiazolidinone intermediate led to the desired compounds in a one-pot procedure. Analytical data and NMR studies confirmed the proposed structure assignment for these compounds.     

13.

Synthesis of cis-Disubstituted Cyclobutenyl Nucleoside Analogues     

M-E. Gourdel-Martin  F. Huet 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):645-648

Abstract

cis-Disubstituted cyclobutene nucleosides analogues were prepared by a linear synthesis starting from cis-cyclobutene dicarboxylic anhydride. This strategy involved mild reaction conditions with intent to restrict the thermal electrocyclic ring opening into (Z,E)-dienes.     

14.

A Novel Synthesis of Antiviral Nucleoside Phosphoramidate and Thiophosphoramidate Prodrugs via Nucleoside H-Phosphonamidates     

Qi Sun  Xingjian Li  Shanshan Gong  Gang Liu  Liang Shen  Liang Peng 《Nucleosides, nucleotides & nucleic acids》2013,32(11):617-638

     

15.

Synthesis of a Base-Protected xylo-LNA Adenine Nucleoside     

《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):1163-1165

Abstract

Synthesis of (1S,3R,4R,7R)-7-hydroxy-1-hydroxymethyl-3-(6-N-benzoyl-adenin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane (2), a base-protected xylo-LNA adenine nucleoside, has been accomplished using a convergent synthetic strategy starting from 1,2-di-O-acetylfuranose 3.     

16.

Synthesis of Nucleoside Analogues Using Immobilised N-Deoxyribosyltransferases     

Nicola Hicks  David W. Hutchinson 《Biocatalysis and Biotransformation》1994,11(1):1-7

Crude N-deoxyribosyltransferase from Lactobacillus leichmannii was immobilised by hydrophobic interaction on octyl-Sepharose or by covalent attachment to poly(acrylamide-co-N-acryl-oxysuccinimide) (PAN). Little enzyme activity was retained by entrapment in K-carrageenan. N-deoxyribosyltransferase immobilised on PAN was used to prepare 2'-deoxy-2-thiouridine.     

17.

Nucleoside Diphosphate Kinase Is a Possible Component of the Ethylene Signal Transduction Pathway   总被引：4，自引：0，他引：4  

Novikova GV  Moshkov IE  Smith AR  Hall MA 《Biochemistry. Biokhimii?a》2003,68(12):1342-1348

In etiolated seedlings of Pisum sativum and leaves of Arabidopsis thaliana, in vivo ethylene treatment resulted in an increase in in vitro phosphorylation of 17 kD (P. sativum) or 16 and 17 kD (A. thaliana) polypeptides. These polypeptides were identified as nucleoside diphosphate kinase (NDPK) based on both biochemical properties and interaction with antibodies against NDPK from P. sativum. Using the receptor-directed antagonist of ethylene action 2,5-norbornadiene and the ethylene-insensitive mutants of A. thaliana etr1-1 and eti5, ethylene specificity and receptor dependence of NDPK phosphorylation have been demonstrated. In pea epicotyls, ethylene treatment also led to increase in nucleoside transferase activity unlike in A. thaliana leaves. The increases in nucleoside transferase activity and NDPK phosphorylation were very rapid and transient. The results suggest a role for NDPK as a possible component of the ethylene signal transduction chain.     

18.

Synthesis of New Acyclic Nucleoside Vinyl Phosphonates     

Annamaria Esposito  Maurizio Taddei 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):985-986

Abstract

Chiral vinyl phosphonates, homomorphous with natural nucleotides, have been prepared starting from (S)-malic acid as potential monomers for the synthesis of acyclic polynucleotides.     

19.

Bicyclic Nucleoside Synthesis—A Photochemical Approach     

E. Lee-Ruff  D. Wells 《Nucleosides, nucleotides & nucleic acids》2013,32(5):484-494

The synthesis of a series of bicyclic nucleosides using photolytic ring-expansion of cyclobutanones is reported. The cyclobutanone precursors were prepared by [2+2] cycloaddition of a series of cyclic alkenes with chlorinated ketenes, derived from dichloro- and trichloroacetyl chloride. The synthesis of the nucleosides was achieved through photolysis of cyclobutanone precursors with 6-chloropurine by UV irradiation. The generality of this method was investigated and the absolute stereochemistry was assigned by NMR spectroscopy. The photoproducts demonstrated a marked preference for the 2′-exo conformation.     

20.

Synthesis of Novel Olefinic Carbocyclic Purine Nucleoside Analogues     

Johanna Wachtmeister  Bjorn Classon  Bertil Samuelsson  Ingemar Kvarnström 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):405-408

Abstract

The synthesis of optically pure unsaturated carbocyclic nucleoside analogues is described. (3,4S)-Bis(t-butyldiphenyl silyloxymethyl)-1R and 1S cyclopent-2-en-1-ol were coupled with 6-chloropurine and 2-amino-6-chloropurine respectively, using a modified Mitsunobu reaction. The products were reacted further using standard procedures to give compounds 12, 14, 16 and 18.     

The Synthesis and Antiviral Activity of Some New S-Adenosyl-L-homocysteine Derivatives and Their Nucleoside Precursors

Abstract

S-Adenosyl-L-homocysteine (SAH) and some of its analogues are potent inhibitors of transmethylation reactions catalysed by S-adenosyl methionine dependent methyltransferases.¹     

The Synthesis of 5-Substituted-2, 4-dimethoxypyrimidines and Some Related Nucleoside Analogues

Abstract

The reaction of 5-formyl-2,4-dimethoxypyrimidine with active methylene compounds in the Knoevenagel reaction and the subsequent nucleoside formation reactions of some of the products was investigated. A new synthesis of (E)-5-(2-bromovinyl)uracil and an improved synthesis of 5-formyl-2′,3′-isopropylidene uridine are reported.     

Synthesis of Novel Polycyclic Nucleoside Analogs

Abstract

We have synthesized polycyclic nucleoside derivatives by a novel, one pot procedure by reacting 4-0-TPS-pyrimidine nucleosides with aromatic diamines. The reaction is limited in scope but provides easy access to certain previously unknown heterocyclic ring systems.₂ 4-0-Triisopro- pylphenylsulfonyl-pyrimidine nucleosides were reacted with aromatic diamines leading to fused, polycyclic ring systems: o-phenylenediamine yielded the pyrimido[1,6-a]benzimidazole, 2.3- diaminonaphthalene gave the naphth[2′,3′:4,5]imidam [1.2-flpyrimidine and 1.8-diaminonaph- thalene led to the pyrimido[l,6-a]perimidine ring system. The reaction is unique because two connected nucleophilic centers react with the pyrimidine nucleoside to form an extended ring system. However, reactions of pyrimidine nucleosides with electrophiles are well known. E.g., reaction of cytidine and adenosine with bromoacetaldehyde yields ethenocytidine and ethenoadenosine) and on reaction of cytidine with 1′-methylthiaminium salts dipyrimido[1,6-a:4′,5′-d]pyrimidine derivatives are obtained.₄ Other polycyclic bases have been made from cytidine and adenosine by photochemical reactions₅.     

Synthesis of a Novel Carbocyclic Nucleoside

Abstract

Carbocyclic nucleoside 1 was prepared from carbomethoxy cyclopentanone in eight steps.     

Synthesis of New Thiazolidinone Nucleoside Analogues

Abstract

The synthesis of new thiazolididone nucleoside analogues is described. Among the different proposed synthetic pathways, the condensation of various nucleic bases using TMSOTf and Et₃N as coupling reagents on a key sulfoxide thiazolidinone intermediate led to the desired compounds in a one-pot procedure. Analytical data and NMR studies confirmed the proposed structure assignment for these compounds.     

Synthesis of cis-Disubstituted Cyclobutenyl Nucleoside Analogues

Abstract

cis-Disubstituted cyclobutene nucleosides analogues were prepared by a linear synthesis starting from cis-cyclobutene dicarboxylic anhydride. This strategy involved mild reaction conditions with intent to restrict the thermal electrocyclic ring opening into (Z,E)-dienes.     

Synthesis of a Base-Protected xylo-LNA Adenine Nucleoside

Abstract

Synthesis of (1S,3R,4R,7R)-7-hydroxy-1-hydroxymethyl-3-(6-N-benzoyl-adenin-9-yl)-2,5-dioxabicyclo[2.2.1]heptane (2), a base-protected xylo-LNA adenine nucleoside, has been accomplished using a convergent synthetic strategy starting from 1,2-di-O-acetylfuranose 3.     

Synthesis of Nucleoside Analogues Using Immobilised N-Deoxyribosyltransferases

Crude N-deoxyribosyltransferase from Lactobacillus leichmannii was immobilised by hydrophobic interaction on octyl-Sepharose or by covalent attachment to poly(acrylamide-co-N-acryl-oxysuccinimide) (PAN). Little enzyme activity was retained by entrapment in K-carrageenan. N-deoxyribosyltransferase immobilised on PAN was used to prepare 2'-deoxy-2-thiouridine.     

Nucleoside Diphosphate Kinase Is a Possible Component of the Ethylene Signal Transduction Pathway

In etiolated seedlings of Pisum sativum and leaves of Arabidopsis thaliana, in vivo ethylene treatment resulted in an increase in in vitro phosphorylation of 17 kD (P. sativum) or 16 and 17 kD (A. thaliana) polypeptides. These polypeptides were identified as nucleoside diphosphate kinase (NDPK) based on both biochemical properties and interaction with antibodies against NDPK from P. sativum. Using the receptor-directed antagonist of ethylene action 2,5-norbornadiene and the ethylene-insensitive mutants of A. thaliana etr1-1 and eti5, ethylene specificity and receptor dependence of NDPK phosphorylation have been demonstrated. In pea epicotyls, ethylene treatment also led to increase in nucleoside transferase activity unlike in A. thaliana leaves. The increases in nucleoside transferase activity and NDPK phosphorylation were very rapid and transient. The results suggest a role for NDPK as a possible component of the ethylene signal transduction chain.     

Synthesis of New Acyclic Nucleoside Vinyl Phosphonates

Abstract

Chiral vinyl phosphonates, homomorphous with natural nucleotides, have been prepared starting from (S)-malic acid as potential monomers for the synthesis of acyclic polynucleotides.     

Bicyclic Nucleoside Synthesis—A Photochemical Approach

The synthesis of a series of bicyclic nucleosides using photolytic ring-expansion of cyclobutanones is reported. The cyclobutanone precursors were prepared by [2+2] cycloaddition of a series of cyclic alkenes with chlorinated ketenes, derived from dichloro- and trichloroacetyl chloride. The synthesis of the nucleosides was achieved through photolysis of cyclobutanone precursors with 6-chloropurine by UV irradiation. The generality of this method was investigated and the absolute stereochemistry was assigned by NMR spectroscopy. The photoproducts demonstrated a marked preference for the 2′-exo conformation.     

Synthesis of Novel Olefinic Carbocyclic Purine Nucleoside Analogues

Abstract

The synthesis of optically pure unsaturated carbocyclic nucleoside analogues is described. (3,4S)-Bis(t-butyldiphenyl silyloxymethyl)-1R and 1S cyclopent-2-en-1-ol were coupled with 6-chloropurine and 2-amino-6-chloropurine respectively, using a modified Mitsunobu reaction. The products were reacted further using standard procedures to give compounds 12, 14, 16 and 18.