Phosphorothioates isomer separations

Nucleoside 2, 3 -cyclic phosphorothioates are prepared by reacting the 5 -acetylnucleoside with triimidazole phosphinsulfide followed by aqueous work-up and deblocking [17]. This procedure is illustrated in Fig. 5 for the exo- and endo-isomers of 2, 3 -cyclic uridine phosphorothioate, 2, 3 -cyclic UMPS, which were first synthesized by Eckstein and associates. The two could be separated because the endo- isomer is crystalline while the other is an oil. After repeated crystallization the pure endo- isomer was obtained and its crystal structure determined, giving its absolute configuration [18]. 

D-Glycerate-2- and -3-[lsO]phosphorothioates have been synthesized by the route outlined in Fig. 10 [29], Methyl D-glycerate was converted to the diastereomeric mixture of exo- and enr/o-D-glycerate cyclic phosphorothioates, which were separated by chromatography. Each isomer was then subjected to hydrolysis with Lil8OH, which was known to occur largely by an in-line mechanism with inversion of... 

Since Nielsen et al introduced peptide nucleic acids (PNA), this area has received vast attention, and continues to do so. More recently, the main area of interest has been in novel analogues, and many new ones have been reported. The solid phase synthesis of DNA-3 -PNA chimeras have been described, in which the DNA is attached to the amino terminal of the PNA via the 3 -phosphate or thiophosphate. All chimeras were shown to have superior thermal stability towards either DNA or RNA than a DNA oligomer, and the phosphodiester linkage was more stable than the phosphorothioate. Hybridisation studies with PNA and PNA-DNA chimeras demonstrate that there is a sequence effect for the junction between PNA and DNA on duplex stability. A decamer pyrimidine bis-PNA oligomer, separated by a linker, when targeted to complementary dsDNA formed three distinct structures. One structure contained two bis-PNA units, and the other two were believed to be structural isomers. 

Systox ), was a mixture of two isomers 0-diethyl 0-ethylmercaptoethyl phosphorothioate (13.34a) and the corresponding thiolate (13.34b). The Bayer company eventually marketed these two components separately, as well as methyl-demeton in which both ethoxy groups had been replaced by methoxy groups. By then, the American systemic agent, dimethoate (13.35) was well established, and a Swiss analogue, phosphamidon (13.33) followed about 1960. These latter two enjoy the current FAO recommendation. 

Rp isomers of dinucleoside phosphorothioates (41,42), nuclease PI is known to catalyze the hydrolysis of their Sp isomers (43). Compounds [all-Rp]-14 and [all-Sp]-14 are in separated experiments incubated with SVPDE and, independently, with nuclease PI. 

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