Novel and Efficient Synthesis of gem -Difluorinated Derivatives of Acyclic Nucleoside Phosphonates (ANPs)

2016 ◽  
Vol 1 (10) ◽  
pp. 2102-2106 ◽  
Author(s):  
Karel Pomeisl ◽  
Petr Beier ◽  
Radek Pohl ◽  
Marcela Krečmerová
Keyword(s):  
Efficient Synthesis ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Derivatives Of

Bifunctional Acyclic Nucleoside Phosphonates. 1. Symmetrical 1,3-Bis[(phosphonomethoxy)propan-2-yl] Derivatives of Purines and Pyrimidines

2006 ◽  
Vol 71 (4) ◽  
pp. 543-566 ◽  
Author(s):  
Silvie Vrbovská ◽  
Antonín Holý ◽  
Radek Pohl ◽  
Milena Masojídková
Keyword(s):  
Biological Activity ◽  
Cytostatic Activity ◽  
Secondary Alcohols ◽  
Phosphonic Acids ◽  
Acyclic Nucleoside Phosphonates ◽  
Pyrimidine Bases ◽  
Acyclic Nucleoside ◽  
Derivatives Of ◽  
Purines And Pyrimidines ◽  
General Method

We report here a general method for the synthesis of new symmetrical bis-phosphonates of acyclic nucleosides. 1,3-Bis[(diisopropoxyphosphoryl)methoxy] derivatives of purine and pyrimidine bases were prepared by their reaction with 1,3-bis[(diisopropoxyphosphoryl)-methoxy]propan-2-yl tosylate. Cytosine, uracil and thymine provided regiospecificallyN1-isomers. This alkylation regiospecificity applies to several other tosylates of primary and secondary alcohols as well. 6-Chloropurine and 2-amino-6-chloropurine were alkylated in N9position. Resulting bis-phosphonates were converted to the respective free phosphonic acids and tested for antiviral and cytostatic activity. Despite the fact that no biological activity was found so far, the outcome of this work can serve as a useful tool in synthesis of novel groups of acyclic nucleoside phosphonates (ANPs).

Bifunctional Acyclic Nucleoside Phosphonates: 2. Symmetrical 2-{[Bis(phosphono)methoxy]methyl}ethyl Derivatives of Purines and Pyrimidines

2007 ◽  
Vol 72 (7) ◽  
pp. 965-983 ◽  
Author(s):  
Silvie Vrbková ◽  
Martin Dračínský ◽  
Antonín Holý
Keyword(s):  
Building Block ◽  
Alkylating Agent ◽  
Cytostatic Activity ◽  
Arbuzov Reaction ◽  
Methyl Ethyl ◽  
Acyclic Nucleoside Phosphonates ◽  
Bisphosphonic Acids ◽  
Acyclic Nucleoside ◽  
Derivatives Of ◽  
Purines And Pyrimidines

Novel bisphosphonate alkylating agent, tetraisopropyl {2-[(mesyloxy)methyl]propane-1,3-diyl}bis(oxymethylene)bisphosphonate 19, was synthesized from diethyl 2,2-bis(hydroxymethyl)malonate. Decarbethoxylation of the diethyl 2,2-dimethyl-1,3-dioxane-5,5-dicarboxylate was followed by chloromethylation of 2-[(benzyloxy)methyl]propane-1,3-diol and Arbuzov reaction with triisopropyl phosphite. Bisphosphonate building block 19 was used in the alkylation of various nucleobases (2-amino-6-chloropurine, adenine, 2-amino-6-(cyclopropyl)aminopurine, cytosine, uracil and 4-methoxy-5-methylpyrimidin-2(1H)-one). N9-Substituted purines and N1-substituted pyrimidines were converted to appropriate free bisphosphonic acids. No antiviral or cytostatic activity was detected.

The efficient synthesis of 2-arylpyrimidine acyclic nucleoside phosphonates using Liebeskind–Srogl cross-coupling reaction

Tetrahedron ◽  
2011 ◽  
Vol 67 (38) ◽  
pp. 7379-7385 ◽  
Author(s):  
Petra Břehová ◽  
Michal Česnek ◽  
Martin Dračínský ◽  
Antonín Holý ◽  
Zlatko Janeba
Keyword(s):  
Coupling Reaction ◽  
Cross Coupling ◽  
Efficient Synthesis ◽  
Cross Coupling Reaction ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside

Efficient synthesis and biological properties of the 2′-trifluoromethyl analogues of acyclic nucleosides and acyclic nucleoside phosphonates

2011 ◽  
Vol 76 (10) ◽  
pp. 1187-1198 ◽  
Author(s):  
Petr Jansa ◽  
Viktor Kolman ◽  
Alexandra Kostinová ◽  
Martin Dračínský ◽  
Helena Mertlíková-Kaiserová ◽  
...  
Keyword(s):  
Biological Properties ◽  
Trifluoromethyl Group ◽  
Efficient Synthesis ◽  
Phosphonic Acids ◽  
Acyclic Nucleosides ◽  
Acyclic Nucleoside Phosphonates ◽  
Dialkyl Phosphonates ◽  
Acyclic Nucleoside ◽  
High Yields ◽  
Very High

Efficient and optimized procedure for the preparation of several acyclic nucleosides and acyclic nucleoside phosphonates substituted at the C-2′ position of the aliphatic part by the trifluoromethyl group is described. Trifluoromethyloxirane was found to be an excellent reagent for the introduction of the 1,1,1-trifluoropropan-2-ol moiety. Surprisingly, the next reaction of these 1,1,1-trifluoropropan-2-ols with the reagent for the introduction of the methylphosphonic residue afforded the desired phosphonates in very high yields and finally a novel simple and scalable procedure for the isolation of free phosphonic acids, after the reaction of dialkyl phosphonates with bromotrimethylsilane, was developed. Prepared compounds were evaluated for their biological properties, but none of the prepared phosphonic acids or acyclic nucleosides exhibits any antiviral, antiproliferative or anti-toxin activities.

scholarly journals Dipyridamole Potentiates the Activity of Various Acyclic Nucleoside Phosphonates against Varicella-Zoster Virus, Herpes Simplex Virus and Human Cytomegalovirus

1994 ◽  
Vol 5 (5) ◽  
pp. 312-321 ◽  
Author(s):  
R. Snoeck ◽  
G. Andrei ◽  
J. Balzarini ◽  
D. Reymen ◽  
E. De Clercq
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Varicella Zoster Virus ◽  
Human Cytomegalovirus ◽  
Varicella Zoster ◽  
Antiviral Effects ◽  
Acyclic Nucleoside Phosphonates ◽  
Acyclic Nucleoside ◽  
Simplex Virus ◽  
Derivatives Of

Dypiridamole (DPM) is widely used in the treatment of cardiovascular diseases as a coronary vasodilator and inhibitor of platelet aggregation. Phosphonylmethoxyethyl (PME) and 3-hydroxy-2-phosphonylmethoxypropyl (HPMP) derivatives of purines and pyrimidines are potent and selective inhibitors of varicella-zoster virus (VZV), herpes simplex virus (HSV) and human cytomegalovirus (HCMV). We have found that DPM markedly potentiates the antiviral effects of the PME derivatives of adenine (PMEA) and 2,6-diaminopurine (PMEDAP), and of the HPMP derivatives of adenine (HPMPA), 3-deazaadenine (HPMPc3A) and cyclic HPMPA (cHPMPA). This was reflected by a significant decrease in the 50% inhibitory concentration of the acyclic nucleoside phosphonates for VZV-, HSV- and HCMV-induced cytopathic effect or plaque formation. DPM did not enhance the activity of vidarabine, acyclovir or ganciclovir. These results were confirmed by virus yield assays (for HSV and HCMV) and flow cytometry (for VZV).

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