Phosphoric oligonucleotide synthesis

Phosphitylation with Azolides of Phosphorous Acid Synthesis of Oligonucleotides... 

This enzymatic deprotection technique can also be successfully applied in oligonucleotide synthesis [18]. Thus,for instance, the pentanucleotide 22 was built up from PhAc-protected guanosine employing the well-established phosphor-... 

This group was developed for 5 protection in acid free oligonucleotide synthesis. It is introduced by the reaction of the sulfenyl chloride with the lithium anion generated from LiHMDS in THF at rt. It is cleaved with l2/CH3CN-pyridine-H20 conditions that simultaneously oxidize phosphite to phosphate. Unlike the 2,4-dinitroben-zenesulfenyl group, it is completely compatible with tervalent phosphorous. ... 

A method for the synthesis of pApUp that uses the triester method has appeared,324 and the concept of phosphorylating preformed oligonucleotides has been extended to the synthesis of 5 -phosphates of di(ribonucleoside) monophosphates by way of phosphoric triester intermediates 325 The terminal 3 -hydroxyl group was protected with the... 

The primary application of LNA has been in antisense therapy due to the aforementioned properties. It has been used to knock down human protein kinase C-a (PKC-ot) with greater efficiency than the corresponding phosphor-othioate ODN, as an inhibitor of human telomerase, to block the synthesis of RNA polymerase II and to inhibit human vascular smooth muscle cell growth. LNA-modified oligonucleotides have also been used in RNA interference (RNAi). ... 

Protective group for nucleosides. Stepwise synthesis of oligonucleotides utilizing 2-cyanoethyl phosphate (1, 172-173) requires protection of the 3 -hydroxyl group which can be cleaved under essentially neutral conditions, since a methoxy-trityl ether is sensitive to acid and a /3-cyanoethyl phosphoric ester is sensitive to alkali. The /3-benzoylpropionyl group meets these requirements, since it is quantitatively cleaved by dilute solutions of hydrazine hydrate in pyridine-acetic acid. The esters are prepared by condensation with DCC (dicyclohexylcarbodiimide). Definitive paper R. L. Letsinger and P. S. Miller, Am. Soc., 91, 3356 (1969)... 

Several reviews of relevance to this chapter have appeared this year. One describes recent advances in the Staudinger reaction another is about the Perkow and related reactions. A comprehensive review has been published on advances in the synthesis of oligonucleotides by the phosphor-amidite approach, and a survey has appeared on the synthesis and cyclisation reactions of tervalent phosphorus acid derivatives containing an oxoalkyl group. ... 

Chemical synthesis of oligonucleotide was also performed using a microfluidic platform. A microfluidic DNA oligonucleotide synthesizer made of PFPE which performs reaction cycles adopted from the widely used phosphor-amidite method was reported [8]. PFPE is an elastomer with excellent chemical compatibility which makes it pos-... 

---