Reaction of sugar epoxides with phosphorothioic acids, evidence of the pentacoordinate phosphorus intermediate in the reaction of 5,6-anhydro-1,2-0-is0propylidene-α-d-glucofuranose with phosphorothioic acids
“…Pseudorotation under acidic conditions favors cleavage of the weaker P−S bond to produce 69 , while basic conditions prohibit pseudorotation, limiting the mechanism to direct displacement of the P−O bond, which leads to the production of 67 . Analysis of related compounds led to the same conclusion of acid-catalyzed cleavage of the P−S bond and base-catalyzed cleavage of the P−O bond. − 12 …”
Section: Hydrolysis Of 3‘-thio-modified Rnamentioning
confidence: 81%
“…Analysis of related compounds led to the same conclusion of acid-catalyzed cleavage of the P-S bond and base-catalyzed cleavage of the P-O bond. [115][116][117] It is of great interest that, over the entire range from pH 10 to pH 14, the 3′-thio-modified RNA 63 was hydrolyzed 2000-fold more rapidly than the corresponding control RNA 1, while acid-catalyzed hydrolysis of 63 was accelerated only 3-fold as compared to that of 1. 114 Since substitution of oxygen by sulfur leads to geometric changes in the backbone that result from elongated bonds and sharpened angles, 51,63,64 the cyclic transition state and, also, intermediates such as 64 and 65 can be stabilized by relief of the strain energy in the five-membered ring.…”
Section: Hydrolysis Of 3′-thio-modified Rnamentioning
“…Pseudorotation under acidic conditions favors cleavage of the weaker P−S bond to produce 69 , while basic conditions prohibit pseudorotation, limiting the mechanism to direct displacement of the P−O bond, which leads to the production of 67 . Analysis of related compounds led to the same conclusion of acid-catalyzed cleavage of the P−S bond and base-catalyzed cleavage of the P−O bond. − 12 …”
Section: Hydrolysis Of 3‘-thio-modified Rnamentioning
confidence: 81%
“…Analysis of related compounds led to the same conclusion of acid-catalyzed cleavage of the P-S bond and base-catalyzed cleavage of the P-O bond. [115][116][117] It is of great interest that, over the entire range from pH 10 to pH 14, the 3′-thio-modified RNA 63 was hydrolyzed 2000-fold more rapidly than the corresponding control RNA 1, while acid-catalyzed hydrolysis of 63 was accelerated only 3-fold as compared to that of 1. 114 Since substitution of oxygen by sulfur leads to geometric changes in the backbone that result from elongated bonds and sharpened angles, 51,63,64 the cyclic transition state and, also, intermediates such as 64 and 65 can be stabilized by relief of the strain energy in the five-membered ring.…”
Section: Hydrolysis Of 3′-thio-modified Rnamentioning
“…Precedent for the selective breakdown of such intermediates has also been reported in the alcoholysis of 5-membered phosphorothioates, in which only P-O bond fission occurs unless reversible conditions are employed, discussed below. 16,17 Sulfur at the 3′-Bridging Position. 3′-S,5′-O-Phosphorothiolate internucleotide linkages, depicted in Figure 4, are cleaved considerably more readily under alkaline conditions than the native phosphodiester bond.…”
Section: Previous Studies Of Thio Effects In Rna Modelsmentioning
The effects of sulfur substitution on the reactions of hydroxyalkyl phosphate esters are examined. These compounds are models for the intramolecular phosphoryl transfer reaction involved in the cleavage of the internucleotide bond in RNA. The models studied here lack the ribose ring and their conformational flexibility results in greater stability and the availability of different reaction pathways. Sulfur in the nucleophilic position shows no nucleophilic reaction at phosphorus, instead rapidly attacking at the beta carbon atom, forming thiirane with departure of a phosphomonoester. Sulfur substitution at either of the two bridging positions leads to cleavage of the diester via formation of a cyclic intermediate, but with significant rate acceleration when compared to the oxygen analogues. The bridge-substituted models react substantially slower than the analogous ribose compounds with sulfur substitution at comparable positions. Kinetic isotope effects reveal significant differences in the transition state depending on which bridging position sulfur occupies. When sulfur is in the scissile bridging position, a highly associative transition state is indicated, with a largely formed bond to the nucleophile and the scissile P-S bond is little changed. When sulfur occupies the other bridging position, the isotope effects imply a very early transition state in a concerted reaction.
“…Michalska has shown that a protected 5,6-epoxy furanose can undergo a ring-opening selectively at the 6-position with either thiophosphoric acids or their alkylammonium salts (Scheme 3). [11,12] Interestingly, he notes that dithiophosphoric acids react most rapidly of the phosphoric acid derivatives he explored. For one product he has further demonstrated that treatment with sodium methoxide quantitatively converts the phosphate adduct into a thiirane with the expected inversion of configuration at the C5-carbon.…”
This micro-review attempts to comprehensively cover reported reactions employing thio-and aminophosphate precursors for forming sulfur and nitrogen heterocycles. All such reactions are triggered by initial formation of an alkoxide, most commonly by attack of a carbon or heteroatom nucleo-
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