1996
DOI: 10.1093/nar/24.19.3811
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Solid support synthesis of all-Rp-oligo(ribonucleoside phosphorothioate)s

Abstract: The first method for solid support synthesis of all-Rp-oligo(ribonucleoside phosphorothioate)s is presented as well as attempts to increase the stereoselectivity of the key step in this approach. The synthetic strategy consists of (i) a solid support synthesis procedure, using 5'-O-(4-methoxytriphenylmethyl)-2'-O-tert-butyldimethylsilyl-ri bon ucleoside 3'-H- phosphonates, that due to stereoselectivity in the condensation step, gives oligomers with mostly Sp-H-phosphonate diesters (72-89% under standard condit… Show more

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Cited by 29 publications
(16 citation statements)
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“…** significantly different from control at P < 0.02 the properties of phosphorothioates have been conducted [72,73]. For example, efforts to develop a method of synthesizing stereodefined phosphorothioate oligoribonucleotides (PS-ORNs) to date have only succeeded in the synthesis of diastereomerically pure dimers or trimers [74,75] and, with moderate stereoselectivity, 4-12-nt all-(Rp) PS-ORNs [76,77]. Chromatographic separation of oligoribonucleotide diastereomers containing phosphorothioate linkages has also been achieved [78].…”
Section: Oligoribonucleotides With Alternating Phosphorothioate Linkagesmentioning
confidence: 99%
“…** significantly different from control at P < 0.02 the properties of phosphorothioates have been conducted [72,73]. For example, efforts to develop a method of synthesizing stereodefined phosphorothioate oligoribonucleotides (PS-ORNs) to date have only succeeded in the synthesis of diastereomerically pure dimers or trimers [74,75] and, with moderate stereoselectivity, 4-12-nt all-(Rp) PS-ORNs [76,77]. Chromatographic separation of oligoribonucleotide diastereomers containing phosphorothioate linkages has also been achieved [78].…”
Section: Oligoribonucleotides With Alternating Phosphorothioate Linkagesmentioning
confidence: 99%
“…This was expected and congruent with literature data. [6] However, in some cases an apparent swap of signals of P-diastereomers (i.e., a high field signal of H-phosphonate diester or a low field signal of the phosphorothioate diester became the major one) was observed.…”
Section: Resultsmentioning
confidence: 99%
“…[1] Particularly, for protected pentavalent nucleotide derivatives, a tendency opposite to that suggested by Eckstein was frequently observed. For example, for ribonucleoside H-phosphonates [2,6] and H-phosphonothioates, [7] the S P diastereomers resonate usually downfield relatively to the R P ones. However, to the best of our knowledge, within the class of particular compounds, no changes in order of chemical shifts between R P and S P were observed; thus, the rule seemed reliable for assigning absolute configuration at the phosphorus centre for closely related compounds.…”
Section: Introductionmentioning
confidence: 99%
“…Another approach that has been developed for the diastereoselective synthesis of (Rp)‐PS oligoribonucleotides involves the condensation of 2′ ‐O‐ tertbutyl‐dimethylsilyl‐5′ ‐O‐ (4‐monomethoxytrityl)‐ribonucleoside 3′‐H‐phosphonate monomers with the 5′‐OH end of a support‐bound nucleoside, followed by 5′‐detritylation to produce a protected oligoribonucleoside H‐phosphonate (Agrawal & Tang, ; Almer et al, ; Battistini, Brasca, Fustinoni, & Lazzari, ; Stawinski, Strömberg, & Thelin, ). Column chromatography using silica gel, RP‐HPLC and anion‐exchange HPLC have all been used successfully for the isolation and separation of diastereomers of the H‐phosphonate diesters with subsequent identification using 31 P NMR or MALDI‐TOF‐MS (Almer, Stawinski, & Stromberg, ).…”
Section: Chirality Of Ps Oligonucleotidesmentioning
confidence: 99%