Aryl H-phosphonates Research Articles

Aryl H-phosphonates. 19. New anti-HIV pronucleotide phosphoramidate diesters containing amino- and hydroxypyridine auxiliaries

We have designed a new type of AZT and ddU phosphoramidate diesters containing various combinations of 2-, 3-, 4-aminopyridine and 2-, 3-, 4-hydroxypyridine moieties attached to the phosphorus center, as potential anti-HIV pronucleotides. Depending on the pKa values of the aminopyridines and the hydroxypyridines used, alternative synthetic strategies based on H-phosphonate chemistry were developed for their preparation. Synthetic aspects of these transformations and the biological activity of the synthesized compounds are discussed.

Oxyonium phosphobetaines – unusually stable nucleophilic catalyst–phosphate complexes formed from H-phosphonates and N-oxides

Aryl H-phosphonates react with N-oxides to form previously unknown stable zwitterionic oxyonium phosphates comprising an −O–P–O–N+Z atom system. Their structures were confirmed i.e. by X-ray crystal structure analysis, and some mechanisms were proposed for their formation. Stability during storage and reactivity toward nucleophiles points to their possible synthetic applications.

Aryl H-Phosphonates 18. Synthesis, properties, and biological activity of 2′,3′-dideoxynucleoside (N-heteroaryl)phosphoramidates of increased lipophilicity

Recently, AZT (N-pyridyl)phosphoramidates were reported as a new type of potential anti-HIV therapeutics. In continuation of that work, here we present new (N-heteroaryl)phosphoramidate derivatives of antiviral 2′,3′-dideoxynucleosides containing other types of N-heteroaryl moieties, particularly those with higher lipophilicity. The present studies comprise mechanistic investigations using 31P NMR correlation analysis, which permitted improvements in the synthetic procedures. The obtained compounds were tested in biological systems to establish their cytotoxicity and anti-HIV activity. The results were analyzed with respect to possible correlations between biological and physico-chemical properties of the phosphoramidates studied, to get some insight into their antiviral mode of action.

New and One Pot Chemoselective Synthesis of Nucleoside 5′-H-Phosphonate Diesters

Arbuzov reaction of phenyl phosphorodichloridite with two equiv of alcohol, or mixture of one equiv of alcohol and one equiv of tert-butyl alcohol, led to the corresponding aryl H-phosphonate diesters. Following displacement of the H-phosphonate diesters with unprotected nucleosides chemoselectively produced nucleoside 5′-H-phosphonate diesters in good yields, respectively.

Aryl H‐Phosphonates. Part 14. Synthesis of New Nucleotide Analogues with Phosphonate—Phosphate Internucleosidic Linkage.

ChemInformVolume 35, Issue 3 Natural Products Aryl H-Phosphonates. Part 14. Synthesis of New Nucleotide Analogues with Phosphonate—Phosphate Internucleosidic Linkage. Marzena Szymczak, Marzena Szymczak Inst. Bioorg. Chem., Pol. Acad. Sci., PL-61-704 Poznan, Pol.Search for more papers by this authorAgnieszka Szymanska, Agnieszka Szymanska Inst. Bioorg. Chem., Pol. Acad. Sci., PL-61-704 Poznan, Pol.Search for more papers by this authorJacek Stawinski, Jacek Stawinski Inst. Bioorg. Chem., Pol. Acad. Sci., PL-61-704 Poznan, Pol.Search for more papers by this authorJerzy Boryski, Jerzy Boryski Inst. Bioorg. Chem., Pol. Acad. Sci., PL-61-704 Poznan, Pol.Search for more papers by this authorAdam Kraszewski, Adam Kraszewski Inst. Bioorg. Chem., Pol. Acad. Sci., PL-61-704 Poznan, Pol.Search for more papers by this author Marzena Szymczak, Marzena Szymczak Inst. Bioorg. Chem., Pol. Acad. Sci., PL-61-704 Poznan, Pol.Search for more papers by this authorAgnieszka Szymanska, Agnieszka Szymanska Inst. Bioorg. Chem., Pol. Acad. Sci., PL-61-704 Poznan, Pol.Search for more papers by this authorJacek Stawinski, Jacek Stawinski Inst. Bioorg. Chem., Pol. Acad. Sci., PL-61-704 Poznan, Pol.Search for more papers by this authorJerzy Boryski, Jerzy Boryski Inst. Bioorg. Chem., Pol. Acad. Sci., PL-61-704 Poznan, Pol.Search for more papers by this authorAdam Kraszewski, Adam Kraszewski Inst. Bioorg. Chem., Pol. Acad. Sci., PL-61-704 Poznan, Pol.Search for more papers by this author First published: 18 December 2003 https://doi.org/10.1002/chin.200403204AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume35, Issue3January 20, 2004 RelatedInformation

Aryl H-phosphonates. Part 13.1 A new, general entry to aryl nucleoside phosphate and aryl nucleoside phosphorothioate diesters

The reaction of nucleoside H-phosphonate monoesters with phenols in the presence of a condensing agent, followed by oxidation of the in-situ-generated aryl nucleoside H-phosphonate diesters with iodine–water or with elemental sulfur, provides a new, ‘one-pot’, efficient entry to nucleoside phosphate or nucleoside phosphorothioate diesters bearing diverse aryl moieties.

Nucleoside phosphate analogues of biological interest, and their synthesis via aryl nucleoside H-phosphonates as intermediates.

This review presents a brief account of the chemistry and mechanistic aspects of aryl H-phosphonates, and selected applications of this class of compounds as intermediates in the synthesis of a wide range of biologically important analogues of nucleoside phosphates, and oligonucleotides, in which the phosphate moieties are replaced by other structurally related groups. The aryl nucleoside H-phosphonates, compounds of controlled reactivity, have proven to be more versatile and superior to various mixed anhydrides as synthetic intermediates, particularly for preparation of nucleotide analogues bearing P-N or P-S bonds in various configurational arrangements at the phosphate moiety.

Aryl H-phosphonates. 12. Synthetic and (31)P NMR studies on the preparation of nucleoside H-phosphonothioate and nucleoside H-phosphonodithioate monoesters.

Transformation of nucleoside H-phosphonate monoesters into the corresponding H-phosphonothioate and H-phosphonodithioate derivatives and possible side-reactions that may accompany this process were studied using (31)P NMR spectroscopy. These provided new insight into a possible mechanism involved in this transformation and constituted the basis for development of efficient methods for the preparation of nucleoside H-phosphonothioate and nucleoside H-phosphonodithioate monoesters using readily available H-phosphonate monoesters as starting materials.

Aryl H-phosphonates. 10. Synthesis of nucleoside phosphoramidate and nucleoside phosphoramidothioate analogues via H-phosphonamidate intermediates

Synthesis of a new type of dinucleoside monophosphate analogue with the 3′–5′ H-phosphonamidate internucleoside linkage, namely thymidin-3′-yl N(thymidin-5′-yl)-H-phosphonamidate 4, was achieved via the reaction of a suitably protected nucleoside aryl H-phosphonate with a 5′-amino-5′-deoxythymidine derivative. The usefulness of 4 as an intermediate for the preparation of various nucleotide analogues was assessed by converting it into the corresponding dinucleoside phosphoramidate and dinucleoside phosphoramidothioate derivatives bearing the PN bond in the bridging position of the phosphoramidate linkage.

31P NMR Studies on Oxidative Transformations of Aryl Nucleoside H-Phosphonate Diesters

Various aspects of oxidative coupling of nucleoside aryl H-phosphonate diesters with nucleosides to produce important synthetic intermediates in the phosphotriester approach to oligonucleotide synthesis, dinucleoside aryl phosphotriesters, was investigated.

Aryl H-phosphonates. Part 11. Synthetic and 31P NMR studies on the formation of aryl nucleoside H-phosphonates †

The formation of aryl H-phosphonate diesters from the corresponding nucleoside 3′-H-phosphonates and various phenols was investigated in detail using 31P NMR spectroscopy. The major reaction pathways of aryl nucleoside H-phosphonates under different experimental conditions have been identified and a general method for a clean and efficient generation of these valuable synthetic intermediates was developed.

Aryl H-phosphonates. 7. Studies on the formation of phosphorus-carbon bond in the reaction of trityl and benzyl halides with dialkyl and diphenyl H-phosphonates

The reactions of H-phosphonate diesters with trityl and benzyl halides were investigated using 31P NMR spectroscopy. It was found that extensive oxidation, which usually accompanies the formation of trityl- or p-nitrobenzylphosphonates from the corresponding alkyl bromides in the Michaelis-Becker reaction, can be considerably suppressed or completely eliminated by reacting p-nitrobenzyl or trityl bromides with diphenyl H-phosphonate in acetonitrile in the presence of DBU.

Use of ammonium aryl H-phosphonates in the preparation of nucleoside H-phosphonate building blocks

Ammonium 4-methylphenyl H-phosphonate 4c was used in the conversion of 5′- O-(dimethoxytrityl)-2′-deoxynucleoside derivatives 6 into the corresponding 3′- H-phosphonates 2, which were isolated in a high state of purity and in high yield.

Studies on aryl H-phosphonates. 3. Mechanistic investigations related to the disproportionation of diphenyl H-phosphonate under anhydrous basic conditions

Diphenyl H-phosphonate undergoes under anhydrous reaction conditions a base-promoted disproportionation to triphenyl phosphite and phenyl H-phosphonate. On the basis of 31P NMR data the most likely mechanism for this transformation was proposed. In order to substantiate these findings and to get a deeper insight into the chemistry of aryl H-phosphonate esters, we carried out also some studies on activation of phenyl and diphenyl H-phosphonates with various condensing agents. We found that aryl vs alkyl esters of phosphonic acid often follow different reaction pathways during the activation, and this can most likely be traced back to higher electrophilicity of the phosphorus centre and to higher reactivity of the P-H bonds in aryl H-phosphonate derivatives.

Aryl H-phosphonates. Part IV. A new method for internucleotide bond formation based on transesterification of aryl nucleoside H-phosphonate diesters

Under mild reaction conditions nucleoside aryl H-phosphonate diesters undergo fast and efficient transesterification with suitably protected nucleosides, affording dinucleoside (3′–5′) H-phosphonate diesters.

Aryl H-phosphonates. Part 5. A simple method for the synthesis of aminoalkyl H-phosphonate monoesters via transesterification of diphenyl H-phosphonate with amino alcohols

Aryl H-phosphonates. Part 5. A simple method for the synthesis of aminoalkyl H-phosphonate monoesters via transesterification of diphenyl H-phosphonate with amino alcohols

31P NMR studies on the activation pathways of aryl H-phosphonate esters with condensing agents

31P NMR studies on the activation pathways of aryl H-phosphonate esters with condensing agents

Synthetic applications of aryl H-phosphonates in nucleotide chemistry

Synthetic applications of aryl H-phosphonates in nucleotide chemistry

Studies on Aryl H-Phosphonates. Synthesis of Nucleoside N-Alkylphosphonamidates

Abstract The aminolysis of aryl nucleoside H-phosphonate diesters with various amines was studied. The new simple and efficient method of synthesis of nucleoside phosphonamidates is described.

Studies on aryl H-phosphonates. I. An efficient method for the preparation of deoxyribo- and ribonucleoside 3′-H-phosphonate monoesters by transesterification of diphenyl H-phosphonate

A convenient method for the preparation of deoxyribonucleoside and ribonucleoside 3′-H-phosphonate monoesters via transesterification of diphenyl H-phosphonate with suitable protected nucleosides in pyridine is described.