Synthesis of Nucleoside Di- and Triphosphates and Dinucleoside Polyphosphates with <i>cyclo</i>Sal-Nucleotides

Warnecke, Svenja; Meier, Chris

doi:10.1021/jo802348h

Cited by 88 publications

(65 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we reported a new chemical route to sugar nucleotides and other phosphorylated biomolecules, such as nucleoside triphosphates, [21] that used cycloSal nucleo-tides [22] as starting materials. For the synthesis of NDP sugars, these active phosphate esters were treated with anomerically pure glycopyranosyl phosphates as nucleophiles with the formation of the pyrophosphate bond.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Nonnatural Nucleoside Diphosphate Sugars

Wolf¹,

Berrio²,

Meier³

2011

Eur J Org Chem

Self Cite

View full text Add to dashboard Cite

Recently, we reported an efficient chemical method for the synthesis of a variety of naturally occurring nucleoside diphosphate (NDP) sugars. This method, which is based on the cycloSal approach, can also be used, in principle, for the preparation of rare or even nonnatural NDP sugars. Herein, the syntheses of sulfoquinovose‐, glucose‐6‐sulfate‐, L‐galactose‐, and 2‐fluoroglycopyranoside‐containing NDP sugars are presented, as well as the synthesis of NDP sugars with non‐natural nucleosides. The reactions described gavestereoisomerically defined NDP sugars in high yields and short reaction times.

show abstract

Section: Introductionmentioning

confidence: 99%

Synthesis of Nonnatural Nucleoside Diphosphate Sugars

Wolf¹,

Berrio²,

Meier³

2011

Eur J Org Chem

Self Cite

View full text Add to dashboard Cite

show abstract

“…The increased yield of the 5′-TP may be explained by the greater solubility and nucleophilicity of tris(tetra-n-butylammonium) hydrogen pyrophosphate relative to bis(tri-n-butylammonium) pyrophosphate. 7) Because our method showed a greatly improved yield of the 5′-TP, we consider that it will not be affected by the sequence of the oligomer or the nature of the 5′-terminal nucleoside or solid support. And, although we have only carried out the triphosphorylation of RNA, we think that our method can be adapted to the triphosphorylation of DNA.…”

Section: Resultsmentioning

confidence: 92%

“…[2][3][4][5][6][7][8][9] Among these, a liquid-phase synthesis of 5′-TPs by reaction of the oligonucleotide with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one (salicyl phosphorochloridite) developed by Ludwig and Eckstein 10) is well known.…”

mentioning

confidence: 99%

Improved Method for the Solid-Phase Synthesis of Oligoribonucleotide 5′-Triphosphates

Nagata

Takagaki

Wada

2012

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

We have developed an improved solid-phase method for the synthesis of 5′-triphosphates (5′-TPs) of oligoribonucleotides. The method is based on the use of salicyl phosphorochloridite as the phosphitylating reagent and the improvement is characterized by the use of the highly reactive pyrophosphorylating reagent tris(tetra-n-butylammonium) hydrogen pyrophosphate instead of the conventional tri-n-butylammonium salt for the nucleophilic substitution reaction to form the cyclic ester intermediate. The improved method can be used to generate oligoribonucleotide 5′-TPs efficiently and reproducibly.Key words 5′-triphosphate; oligoribonucleotide; solid phase; RNA; triphosphorylation 5′-Triphosphates (5′-TPs) of nucleosides and nucleic acids play an important role in biochemical reactions and have many research and medical applications. Thus, nucleoside 5′-TPs have long been known to be substrates for enzymatic DNA and RNA synthesis. A more recent discovery is the fact that the immune response triggered by the binding of 5′-TPs of RNA oligomers to retinoic acid-induced protein I (RIG-I) works together in synergy with gene silencing mediated by small interfering RNAs to promote apoptosis in tumor cells. 1)As for applications, 5′-TPs of DNA and RNA oligomers are used as substrates for ligation in vitro, while modified nucleoside triphosphates are used as antiviral medicines and diagnostic reagents. The demand for 5′-TPs of DNA and RNA is increasing and will most likely be met by chemical synthetic rather than enzymatic methods because of advantages resulting from the ability to introduce chemically modified nucleosides at any point in the sequence as well as the practicality of scaling up the synthesis. Chemical methods for the synthesis of 5′-TPs of RNA in particular have the additional advantage that they allow the production of highly pure RNA.A number of chemical syntheses of 5′-TPs of DNA and RNA have been reported. 2-9) Among these, a liquid-phase synthesis of 5′-TPs by reaction of the oligonucleotide with 2-chloro-4H-1,3,2-benzodioxaphosphorin-4-one (salicyl phosphorochloridite) developed by Ludwig and Eckstein 10) is well known.11) However, there are few reports of the solid-phase synthesis of DNA and RNA 5′-TPs. 4,9,11) A solid-phase adaptation of the salicyl phosphorochloridite method of Ludwig and Eckstein 10) has been developed by Schmidt et al.,12) who used it to synthesize the 5′-TP of a 25-mer RNA.For triphosphorylation experiments in the present study, we synthesized a 25-mer RNA oligomer by the 2-cyanoethoxymethyl (CEM) method of RNA synthesis developed in our laboratory. [13][14][15] In this method, the CEM group is used as the 2′-hydroxyl protecting group. Because the CEM group is small, it offers minimal steric hindrance and so allows an increased yield at each coupling step. As a result, and also because of the ease of removal of the CEM group under mild conditions after synthesis, RNA can be synthesized more simply and easily by the CEM method than by methods involving conventional 2′-hydroxyl protect...

show abstract

“…Entecavir (BMS-200475), commercialized as Baraclude ® , is a guanosine carbocyclic analog, first patented by Bristol-Meyer Squibb as a nanomolar (EC 50 = 3.75 nM) inhibitor of HBV polymerase [17]. After the bioconversion to its triphosphate form, it hinders the viral DNA replication cycle while maintaining substantial features: pharmacokinetic stability [18], low cytotoxicity (CC 50 = 3 μM) [19] and low viral DNA mutagenic properties [20]. Therefore, these attributes translated into a breakthrough for the clinical treatment of HBV chronic infection, upon marketing in 2005, whereas counterparts of entecavir, such as lamivudine and adefovir, showed limitations such as genetic mutation of the virus and, thus, drug resistance [21].…”

Section: Synthesis Of the Anti-hbv Entecavir And Its Novel Class Of Anamentioning

confidence: 99%

Recent Progress for the Synthesis of Selected Carbocyclic Nucleosides

et al. 2015

View full text Add to dashboard Cite

Nucleoside analogs are extremely useful for the development of therapeutic agents to control viral diseases and cancer. Among the numerous modifications on the nucleoside skeleton, replacement of the oxygen of the furanose ring by a CH2 group resulted in increased flexibility and higher resistance to phosphorylases and led to carbocyclic nucleoside analogs (or carbanucleosides). The broad spectrum of biological activities of carbocyclic nucleosides led to tremendous research interest in their syntheses. The article documents recent strategies for the synthesis of active carbocyclic nucleosides by presenting individual case studies, such as the neplanocins, entecavir and selected fluorinated carbocyclic nucleosides. Furthermore, it provides new insights into new directions for more potent and active carbocyclic nucleoside analogs.

show abstract

Synthesis of Nucleoside Di- and Triphosphates and Dinucleoside Polyphosphates with cycloSal-Nucleotides

Cited by 88 publications

References 37 publications

Synthesis of Nonnatural Nucleoside Diphosphate Sugars

Synthesis of Nonnatural Nucleoside Diphosphate Sugars

Improved Method for the Solid-Phase Synthesis of Oligoribonucleotide 5′-Triphosphates

Recent Progress for the Synthesis of Selected Carbocyclic Nucleosides

Contact Info

Product

Resources

About