Oligonucleosides

The trimethoxy derivative is too labile for most applications, but the mono and diderivatives have been used extensively in the preparation of oligonucleotides and oligonucleosides. The monomethoxy derivative has been used for the selective protection of a primary allylic alcohol over a secondary allylic alcohol (MMTr, Pyr, -10°). ... 

No phosphitylation of biotin nitrogen N2 was observed under these reaction conditions. The phosphoroamidite formed was designed for direct use in automated DNA synthesized using standard phosphoroamidite chemistry to introduce a photocleavable biotin label on the 5 -terminal phosphate of synthetic oligonucleosides. 

Example 55 iV,iSr-diisopropyl-4-nitrophenylmethylphosphonoamidite has been applied in the synthesis of oligonucleoside methylphosphonates [89]. This stable crystalline compound prepared from methyldichlorophosphine, was employed in two ways in a procedure similar to that presented in the Examples 42 and 43. 

Especially attractive was the possibility to connect nucleosides, as has been realized, for instance, with the hexathymidine 141 and with the elongated and alternating strands 142 and 143. These compounds represent artificial oligonucleosides, which may interact with natural polynucleotides or nucleic acids. On treatment with Cu(i), 142 and 143 gave the double-helical complexes 144 and 145, respectively, inside-out analogues of double-stranded nucleic acids, which may be termed deoxy-... 

Bardella F, Eritja R, Pedroso E, Giralt E, Gel-phase 31P-NMR. A new analytical tool to evaluate solid phase oligonucleoside synthesis, Bioorg. Med. Chem. Lett., 3 2793-2796, 1993. 

Jayaraman, K., McParland, K., Miller, P., and Tso, P.O.P. 1981. Non-ionic oligonucleoside methylphosphonates. 4. Selective inhibition of Escherichia coli protein synthesis and growth by non-ionic oligonucleotides complementary to the 3 end of 16S ribosomal-RNA. Proc. Natl. Acad. Sci. U.S.A. 78 1537-1541. 

Shaw has reviewed the various approaches to the synthesis of organophos-phate-oligonucleosides and has further commented on their chemical and biophysical properties along with their interactions with various enzymes such as DNA-polymerases, and compared them to other members of the family of phosphorus modified nucleic acids. She also reported the synthesis of P-tyrosinyl(P-0)-5 -P-nucleosidyl boranophosphates (23a,b), as antiviral and anticancer prodrug candidates. The P-boranophosphates were prepared by reacting a phosphoramidite intermediate obtained from protected tyrosine and the protected nucleoside in the presence of IH-tetrazole, followed by in situ borona-tion of the phosphite triester intermediate. The two diastereomers were then separated by reverse-phase HPLC. ... 

Tris(hexafluoroisopropyl) phosphite (105) has been used to prepare ribonucleoside H-phosphonates (106), and deoxyribo-nucleoside phosphites (107) ° both were used as monomers to prepare oligonucleoside H-phosphonates on a solid support, with W-methylimidazole as catalyst for the coupling of (107). Several new alkyl phosphorodiamidites (108) and (109) have been used... 

Deoxyribonucleotides, deoxyribonucleotide phosphorothioates, modified DNA, and analogs have wide applications in molecular biology, antisense applications, antigene therapy, etc. Three methods are available for the synthesis of oligonucleoside phosphorothioates phosphoramidite, H-phosphonate, and phospho-... 

Several new sulfur transfer reagents for the oxidation of oligonucleoside phosphites to phosphorothioates have been proposed this year. These include the disulfonyldisulfides (23), and the two cyclic disulfides (24) and (25). ... 

Oligonucleoside phosphorodithioates containing all four nucleobases and up to twenty... 

The volume concludes with the preparation of four useful reagents and compounds. Oligonucleoside phosphorothioates may be prepared using... 

The reactions of bis(phosphoryl) disulphides with a variety of tervalent phosphorus acid derivatives or triphenylphosphine have been studied by means of low-temperature n.m.r. Intermediates were detected which indicated initial attack on one sulphur atom followed by substitution reactions at one of the phosphorus atoms, Arbuzov dealkylations, or phosphorane formation. An example is shown for the reaction of tributyl phosphite with bis(diethoxyphosphoryl) disulphide (25). In order to obtain solely thiophosphate products it is necessary to use bis(thiophosphoryl) disulphides, and one such compound (26) has been proposed as a highly effective reagent for the oxidation of oligonucleoside phosphites to phosphorothioates. A comparison of the efficiency of (26) with that of four other sulphurizing agents for use in... 

Three papers have appeared on the solid support synthesis of oligonucleoside-peptide hybrids, using different solid supports and protection group strategy. ... 

Chemistry and properties of nucleoside and oligonucleoside boranopho-sphates 07CRV4746. 

Coupling of di- or oligo-nucleosides having H-phosphonate at the 3 -position with a second mono- or oligo- nucleoside having a free 5 -hydroxyl group results in the formation of oligonucleosides (n > 2) [174],... 

In the area of modified intemucleosidic links, the use of the selenium-containing system 186 in the synthesis of oligonucleoside phosphorothioates has been prefmed to the earlier sulfur analogue since the P-Se bond is more labile in reaction with the 5 -OH group of the other... 

Dioxide. The sulfur-transfer reagent 3//-l,2-benzodithiol-3-one 1,1-dioxide (2, eq 1) is widely used in the preparation of oligonucleoside phosphorothioates, which are especially valuable in the development of therapeutic oligonucleotides against various t)q)es of cancer and infectious diseases in humans. ... 

The scope of this report is not to provide an exhaustive list of all oligonucleoside phosphorothioates that have been prepared using 2, but to review those critical issues stemming from the preparation and handling of the reagent along with specific applications of 3H-... 

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