118149-25-0Relevant academic research and scientific papers
Synthesis of Oligo(deoxyribonucleoside phosphorodithioate)s by the Dithiaphospholane Approach
Okruszek, Andrzej,Sierzchala, Agnieszka,Fearon, Karen L.,Stec, Wojciech J.
, p. 6998 - 7005 (2007/10/03)
A novel method of synthesis of oligo(deoxyribonucleoside phosphorodithioate)s (S2-ODNs), based on the ring-opening condensation of nucleoside 3'-O-(2-thiono-1,3,2-dithiaphospholane)s with 5'-O-deprotected nucleosi(ti)des in the presence of a strong organic base such as DBU, is presented.The process has been adapted to the requirements of automated solid-phase oligonucleotide synthesis with a relatively short condensation step (5 min) and reasonable step-yield (>95percent).N-Methylpyrrolidin-2-ylidenyl (Pya) was found to be the group of choice for the protection of reactive aminofunctions of nucleobases in nucleotide substrates.Sarcosine-containing linker (LCA CPG SAR) was employed due to its known resistance to cleavage by DBU.Several medium-size S2-ODNs were prepared by this approach.Their identity and purity was confirmed by means of 31P NMR, gel electrophoresis, and mass spectrometry.It has been demonstrated that, contrary to a recent report, S2-ODNs are not degraded by DNaseI.
Synthesis of deoxydinucleoside phosphorodithioates
Brill, Wolfgang K.-D.,Nielsen, John,Caruthers, Marvin H.
, p. 3972 - 3980 (2007/10/02)
The synthesis of a new class of DNA analogues called phosphorodithioate DNA is described. This analogue, which has a deoxynucleoside-OPS2O-deoxynucleoside internucleotide linkage, is isosteric and isopolar with the normal phosphodiester, inert toward nucleases, and potentially useful for a large number of biochemical and biological applications. Two methods are described for synthesizing this derivative. One route begins by condensing a deoxynucleoside phosphorodiamidite with a second appropriately protected deoxynucleoside to yield a deoxydinucleoside phosphoramidite. Sulfhydrolysis with H2S generates the H-phosphonothioate, which upon oxidation with sulfur yields the deoxydinucleoside phosphorodithioate. Alternatively, sequential treatment of the deoxydinucleoside phosphoramidite with a mercaptan and sulfur yields the deoxydinucleoside phosphorodithioate triester. These deoxydinucleotides in protected form can then be used to introduce the dithioate internucleotide linkage into DNA. The second route for generating dithioate DNA uses deoxynucleoside phosphorothioamidites. Two derivatives, the deoxynucleoside 3′-N,N-dimetnyl- or 3′-(N,N-tetramethylenephosphorothioamidite), were found to be especially attractive synthons as they could be prepared in stable form via a one-flask synthesis procedure and used to form the deoxydinucleoside thiophosphite rapidly (1-2 min with tetrazole as activator) in high yield. Subsequent oxidation with sulfur generates the completely protected phosphorodithioate linkage.
Deoxyribonucleoside Phosphorodithioates. Preparation of Dinucleoside Phosphorodithioates from Nucleoside Thiophosphoramidites
Dahl, Bjarne H.,Bjergarde, Kirsten,Sommer, Vibeke B.,Dahl, Otto
, p. 896 - 901 (2007/10/02)
A series of protected thymidine thiophosphoramidites have been prepared and their properties evaluated.Although less reactive than phosphoramidites, thiophosphoramidites with small N-substituents (methyl) are useful synthons for the preparation of nucleoside phosphorodithioates, as demonstrated by the preparation of a thymidine dimer.The coupling reactions are not as clean as those of the analogous phosphoramidites since the alkylthio group is somewhat labile.
