Oligodeoxyribonucleotides protecting groups

As mentioned in last year s Report, aromatic phosphoramidates have been used to protect 5 -phosphoryl groups in the stepwise synthesis of oligodeoxyribonucleotides. The appropriate monomer units are coupled with DCC and the phosphoramidate protecting group is removed when required with isoamyl nitrite. A rapid and general preparative method for oligonucleotides has been developed based on phosphoramidates of the highly lipophilic 4-aminophenyltriphenylmethane (25). Purification of... 

Protecting groups that were mounted on the deoxynucleosides, it will be recalled, are all amides (A -benzoyl and A -butryl), and, along with the one that remains on the phosphate backbone (cyanoethyl), are all easily removed when the synthesis of the completed oligodeoxyribonucleotide is finished, by treatment with concentrated ammonium hydroxide. 

The use of 3 -0-formyl esters as protecting groups in the synthesis of oligodeoxyribonucleotides is discussed in Chapter 19-Reaction of perbenzylated glucose with acyl fluorides in the presence of caesium fluoride has been shown to be an excellent method for preparing the glycosyl ester (Scheme 1). Under these essentially neutral conditions yields of between 90 and 100% of (,y( -anomers were obtained, the anomeric ratio being controlled by... 

Using method a, oligodeoxyribonucleotides were synthesized from di- to deca-deoxyribonucleotides by means of mesitylenesulfonylimidazole and mesitylenesulfonyl-1,2,4-triazole. With triisoproylbenzenesulfonylimidazole die condensation took place more slowly.11121 Compared widi the corresponding arylsulfonyl chlorides, imidazolides induced intemucleotide condensation much more slowly, but caused no darkening of the reaction mixture, did not affect acid-sensitive bonds in trityl protected nucleotides, and did not sulfonate the 3 -hydroxy groups.11111 The reaction conditions were room temperature, 5—6 days, and pyridine as solvent.11111... 

Oligoribonucleotides are more difficult to handle than oligodeoxyribonucleotides, mainly because of their sensitivity towards nucleases. For the synthesis of oligoribonucleotides on insoluble supports, protection of the 2 -hydroxyl group is required, which must be stable towards oxidation with iodine and the acidic conditions of DMT depro-... 

---