Efficient One-Pot Synthesis of 2‘-Deoxyribonucleoside 3‘-<i>O</i>- and 5‘-<i>O</i>-Phosphorodithioates

Okruszek, And̀rzej; Olesiak, Magdalena; Krajewska, D; Stec, Wojciech J.

doi:10.1021/jo961801g

Cited by 28 publications

(24 citation statements)

References 15 publications

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“…It is worthwhile to mention that an analogous dithiaphospholane approach was applied earlier for the preparation of phosphorodithioate derivatives of deoxyribonucleosides. 26 Further studies on the application of oxathiaphospholane approach for thiophosphorylation of thiols and amines are underway. …”

Section: Methodsmentioning

confidence: 99%

Thiophosphorylation of Biologically Relevant Alcohols by the Oxathiaphospholane Approach

Olesiak¹,

Krajewska²,

Wasilewska³

et al. 2002

Synlett

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2-Alkoxy-2-thiono-1,3,2-oxathiaphospholanes are readily transformed into phosphorothioate monoesters of the corresponding alcohols in a one-pot process, involving the reaction with 3-hydroxypropionitrile in the presence of DBU, followed by treatment with aqueous ammonia. In this way a series of nucleoside-3¢-O-and 5¢-O-phosphorothioates were prepared, as well as phosphorothioate derivatives of selected polyols.Nucleoside phosphoromonothioates, originally introduced by Eckstein, 1 became an important tool for studying the mechanisms of action of nucleolytic enzymes 1-3 and are widely employed as intermediates in the synthesis of other phosphorothioate derivatives of nucleosides. 4 The procedure employed by Eckstein 1 involved the treatment of appropriately protected nucleoside with thiophosphoryl tris-imidazolide. The procedure was not very efficient and was limited to the synthesis of nucleoside 5¢-O-phosphorothioates. For the synthesis of this class of compounds much a more convenient methodology was introduced by Murray and Atkinson 2 who treated unprotected adenosine with thiophosphoryl chloride in triethyl phosphate as a solvent. This approach was further extended to other nucleosides in both the ribo-5 and deoxyribonucleoside series. 6 Another example of 5¢-O-thiophosphorylation of unprotected nucleosides was described by Chen and Benkovic 7 who treated nucleoside with phosphorous acid in the presence of DCC, followed by sulfurization of resulting nucleoside 5¢-O-H-phosphonate with elemental sulfur. Other procedures, which were described in the literature for thiophosphorylation of nucleosides required selective protection of reactive groups at the sugar and/or nucleobase moiety. Thus, the synthesis of thymidine 3¢-O-phosphorothioate was accomplished by treatment of 5¢-O-protected thymidine with thiophosphoryl chloride in the presence of pyridine followed by work-up with alkali. 8 An efficient thiophosphorylation of 3¢-O-or 5¢-O-protected nucleosides was also performed by Cook, 9 with S-2-carbamoylethyl phosphorothioate in the presence of DCC as condensing agent. In a similar manner S-2-cyanoethyl phosphorothioate was employed for introducing of phosphorothioate functions into nucleoside moiety. 10 In both cases the S-protecting groups were selectively removed by postsynthetic work-up with alkali. More recently, the phosphoramidite methodology was successfully adopted for both 5¢-O-and 3¢-O-thiophosphorylation of nucleosides. 11,12 The procedure involved phosphitylation of appropriately protected nucleoside with reagents such as bis(2-cyanoethoxy)-N,N-diisopropylaminophosphoramidite, 11 bis[2-(4-nitrophenyl)-ethoxy]-N,N-diisopropylaminophosphoramidite, 11a or 2-cyanoethoxy-2-(dimethoxytrityloxyethylsulfonyl)-ethoxy-N,N-diiso-propylaminophosphoramidite 12 in the presence of tetrazole, followed by sulfurization with elemental sulfur. The phosphorothioate O-protecting groups were removed by b-elimination by treatment with appropriate base. In addition to nucleosides, the phosphoramidite methodology was successf...

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Section: Methodsmentioning

confidence: 99%

Thiophosphorylation of Biologically Relevant Alcohols by the Oxathiaphospholane Approach

Olesiak¹,

Krajewska²,

Wasilewska³

et al. 2002

Synlett

Self Cite

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“…41,43 Suspecting the phosphorotrithioates might be unstable at neutral pH after extended periods, we again attempted to prepare dTTT-PS3 on the synthesis column and quickly purified and analyzed the suspected dTTT-PS3 product by ESI mass spectrometry. Purified samples stored in pH neutral and pH 9.0 buffers revealed an ion peak corresponding to dTTT-PS3.…”

Section: Synthesis Strategymentioning

confidence: 99%

New, stronger nucleophiles for nucleic acid-templated chemistry: Synthesis and application in fluorescence detection of cellular RNA

Miller¹,

Silverman²,

Kool³

2008

Bioorganic & Medicinal Chemistry

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Nucleic acid-templated chemistry is a promising strategy for imaging genetic sequences in living cells. Here we describe the synthesis of two new nucleophiles for use in templated nucleophilic displacements with DNA probes. The nucleophilic groups are phosphorodithioate and phosphorotrithioate; we report on synthetic methods for introducing these groups at the 3′-terminus of oligonucleotides. Both new nucleophiles are found to be more highly reactive than earlier phosphoromonothioates. This increased nucleophilicity is shown to result in more rapid templated reactions with electrophilic DNA probes. The new probes were demonstrated in detection of specific genetic sequences in solution, with clear signal over background being generated in as little as 20 min. The probes were also tested for imaging ribosomal RNA sequences in live E. coli; useful signal was generated in 20 min to one hour, approximately one quarter to one-half the time of earlier monothioate probes, and the signal-to-noise ratio was increased as well.

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“…Carbohydrate phosphates have been the subject of study of nucleosides and their prodrugs with improved cellular permeability and antiviral or anticancer activities . Monothiophosphorylated and dithiophosphorylated carbohydrates were also obtained . Meanwhile, due to their chirality at the phosphorus center and higher stability toward enzymatic hydrolysis, phosphorothioate derivatives have proven to be valuable as model constructs for designing enzyme‐catalyzed phosphoryl transfer reactions .…”

Section: Introductionmentioning

confidence: 99%

“…Meanwhile, due to their chirality at the phosphorus center and higher stability toward enzymatic hydrolysis, phosphorothioate derivatives have proven to be valuable as model constructs for designing enzyme‐catalyzed phosphoryl transfer reactions . Common methods of synthesizing monothiophosphorylated and dithiophosphorylated carbohydrates are usually based on the reaction of phosphorothioic acids with sugar oxiranes, photochemical addition of diethyl thiophosphonate to unsaturated sugars, reaction of unprotected nucleosides with 2‐( N , N′ ‐di‐ iso ‐propylamino)‐1,3,2‐oxathiaphospholane in the presence of 1 H ‐tetrazole followed by sulfurization with Beaucage's reagent, reaction of O ‐acetyl protected thymine, cytosine, adenine, or guanine nucleosides with 2‐( N,N′ ‐di‐ iso ‐propylamino)‐ or 2‐chloro‐1,3,2‐oxathiaphospholanes followed by sulfurization with elemental sulfur, or reaction of nucleoside H ‐phosphonate monoesters with hydrogen sulfide in the presence of pivaloyl chloride . As a rule, protection of some hydroxyl groups of monosaccharides and deprotection procedure are required .…”

Section: Introductionmentioning

confidence: 99%

“…As a rule, protection of some hydroxyl groups of monosaccharides and deprotection procedure are required . Thus, O ‐acyl protection of hydroxyl groups is usually used to obtain nucleoside dithiophosphates and trithiophosphates . Isopropylidene moiety have been reported to be a more efficient protecting group to prepare α‐ d ‐glucofuranose and α‐ d ‐allofuranose dithiophosphates and their nucleotide derivatives …”

Section: Introductionmentioning

confidence: 99%

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α‐d‐Glucofuranose and α‐d‐allofuranose diacetonides and silyl ether of α‐d‐glucofuranose diacetonide in dithiophosphorylation reactions

Низамов

Nikitin

Belov

et al. 2016

Heteroatom Chemistry

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α‐d‐Glucofuranose and α‐d‐allofuranose diacetonides react with 2,4‐diorganyl 1,3,2,4‐dithiadiphosphetane‐2,4‐disulfides to form optically active dithiophosphonates in 78–81% yields, which are transformed into the corresponding ammonium salts in 90–97% yields by the treatment of n‐hexadecylamine. The S‐silyldithiophosphonate was prepared in 93% yield by the reaction of 2,4‐bis(butoxyphenyl) 1,3,2,4‐dithiadiphosphetane‐2,4‐disulfide with silyl ether of α‐d‐glucofuranose diacetonide. One of the salts obtained possesses antibacterial activity against Staphylococcus aureus ATCC 6538‐P.

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Efficient One-Pot Synthesis of 2‘-Deoxyribonucleoside 3‘-O- and 5‘-O-Phosphorodithioates

Cited by 28 publications

References 15 publications

Thiophosphorylation of Biologically Relevant Alcohols by the Oxathiaphospholane Approach

Thiophosphorylation of Biologically Relevant Alcohols by the Oxathiaphospholane Approach

New, stronger nucleophiles for nucleic acid-templated chemistry: Synthesis and application in fluorescence detection of cellular RNA

α‐d‐Glucofuranose and α‐d‐allofuranose diacetonides and silyl ether of α‐d‐glucofuranose diacetonide in dithiophosphorylation reactions

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