Phosphotriester approach

The trifluoroethyl group was used as an activating group in the phosphotriester approach to oligonucleotide synthesis, as well as a protective group that could be removed with 4-nitrobenzaldoxime (tetramethylguanidine, dioxane, H20). ... 

PhosphorylationThis reagent can be used for 3 -and/or 5 -phosphorylation of nucleosides in the phosphotriester approach to oligonucleotides. Deblocking by / -elimination proceeds cleanly with DBU in pyridine at 25" in 24 hours. 

Kamaike K, Hasegawa Y, Ishido Y, Efficient synthesis of an oligonucleotide on a cellulose acetate derivative as a novel polymer-support using a phosphotriester approach, Tetrahedron Lett., 29 647-650, 1988. 

There are three widely used chemistries for oligodeoxynucleotide synthesis, and all have been successfully transferred onto SP. The first is the so-called phosphotriester approach (71), which is shown in Fig. 2.9. In this method a 5 -protected nucleoside... 

Chladek have synthesised GGA aminoacylated at the 2 (3 )-position with phenylalanine. The oligoribonucleotide was assembled by the stepwise phosphotriester approach using (72) as the building block for the incorporation of guanosine. Aminoacylation of the trinucleotide was performed using... 

Adenyl-(2 -5 )-adenyl-(2 -5 )-8-azidoadenosine has been prepared by the phosphotriester approach from building blocks containing a 3 -O-(A-nitrophenyl)-ethylsulphonyl group (137). The trinucleotide has been used to label RNase L in L929 cells by uv irradiation in cell culture. A review on the photoreactions of nucleic acids and their constituents with amino acids and related compotinds has recently been published. The affinity analogues of cAMP, 2-[(A-bromo-... 

Another prodrug form of acyclovir, l-O-hexadecylpropanediol-3-phos-phate-acyclovir (10), an orally bio-available lipid prodrug, has been synthesised from acyclovir using 2-chlorophenyldichlorophosphate in a phosphotriester approach and evaluated in vitro and in vivo against HSV-1. 

The phosphotriester approach solves some of the problems of the phosphodi-ester method. More recently, the phosphite-triester method has been introduced this makes use of the extreme reactivity of the phosphite reagent, i.e., the two building blocks are joined in a few minutes compared with the hours required by the phosphodiester approach. 

Phase transfer catalysis4 is a valuable tool in organic synthesis. The process is exemplified by the convenient synthesis of 2-chlorophenyl phosphoro-dichloridothioate. Using this phase transfer reaction, a number of dichloridothioates of substituted phenyl, benzyl, thiophenyl, and thiobenzyl alcohols are accessible. The phosphorodichloridothioate reacts with various coupling reagents to form activated species that are useful in the synthesis of oligonucleotide phosphorothioates via the phosphotriester approach as illustrated below.5 6... 

Miyoshi KI, Huang TH, Itakura K. Solid-phase synthesis of polynucleotides Synthesis of polynucleotides with defined sequences by the block coupling phosphotriester approach. Nucleic Acids Res 8 5491-5505, 1980. 

A series of aryl b(s-(nucleoside-5 -yl)phosphates in which the nucleosides are either 2, 3 -dideoxy (d2) or 2, 3 -didehydro-2, 3 -dideoxy (d4) has been prepared by coupling the nucleoside moieties together using a standard phosphotriester approach. Only the 4-(methyl-sulphonyOphenyl derivatives of d4T (13) and d2A (14) showed anti-HIV activity that was comparable with the parent nucleosides. The activity of these compounds can be explained by uptake of the triesters into cells followed by a slow release of the niKleoside and nucleotide. A similar strategy has been adopted by Meier and Huynh-Dinh based on the recent observe-... 

The oligomers were prepared by a phosphotriester approach using synthons with the general 132... 

Phosphorylation, This reagent is useful for the first step in the phosphotriester approach to oligonucleotide synthesis,which involves conversion of a free 3 -hydroxy group of a protected nucleoside into a phosphotriester of type 3. Treatment of 3 with p-thiocresol and triethylamine at 20° leads to the triethyl-... 

G. General Method of Oligonucleotide Synthesis by the Modified Phosphotriester Approach... 

Figure 8. General approach of deoxyoligonucleotide synthesis by the modified phosphotriester approach.

E. M. Ivanova, L. M. Khalimshaya, V. P. Romanenko, and V. F. Zarytova, Pyrophosphate tetraester intermediate of coupling reactions in the phosphotriester approach to the synthesis of deoxyoligoribonucleotides, Tetrahedron Lett., 23, 5447 (1982). 

Although (1) has not been used in solid-phase oligonucleotide synthesis, another more stable arylsulfonyl derivative, l-(mesityl-sulfonyl)-3-nitro-l,2,4-triazole (MSNT), is commonly used in that strategy by the phosphotriester approach. ... 

A review of the chemical synthesis of oligo- and poly-nucleotides by the phosphotriester approach has appeared. ... 

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