Phosphoramidites modification

The a-anomeric form of a 2 -deoxyribose, which has the base inverted with respect to the natural P-anomeric form, can be synthesized by using the phosphoramidite method sugar modification renders the derivatives nuclease-resistant. These analogues form parallel duplexes with complementary RNA... 

Advances in Mechanistic Understanding and Catalyst Design Cyclometalation and Modification of the Phosphoramidite Ligand... 

Additional studies were conducted to determine how further modifications to the amine portion of the phosphoramidite ligand affect iridium-catalyzed allylic substitution. One arylethyl moiety is necessary for the formation of metalacyclic active catalyst, but it was unclear how changes to the structure of the second substituent on nitrogen would affect reactivity and selectivity. A stereocenter on this second... 

The drawbacks of the synthetic approach include the effort in preparation of the spin-labeled phosphoramidites and exposure of the spin label to the conditions of the chemical synthesis. The latter also applies for methods that use on-column modification during the synthesis (Piton et al., 2007 Schiemann et al., 2004). For example, the iodine solution that is commonly used for the phosphorous oxidation during the synthesis reduces nitroxides... 

Alternatively to the DNA modifications in the previous two sections where the chromophore was attached to one of the four DNA bases, chromophores can be incorporated as artificial DNA bases substituting a natural base or even a whole base-pair. There is a large number of recently reported syntheses of chromophores as DNA base surrogates, e.g. flavine derivatives [26] and thiazole orange derivatives [42]. Additionally, a variety of phosphoramidites as DNA building blocks for the introduction of fluorophores into DNA are commercially available, e.g. acridine derivatives. Clearly, the synthetic protocols for this kind of DNA modification do not follow a principle strategy which can be applied in a versatile fashion, as is the case for the DNA base modifications mentioned in the previous sections. It is important to point out that in many cases it turned out to be useful to replace the 2 -deoxyribose moiety with acyclic linker systems. This was also the case during our attempts to synthesize ethidium-modified DNA, which will be described here briefly. 

The binaphthol-based Feringa phosphoramidite 1 and its more sterically demanding modification 76 were goods ligands for the reaction with nitroalkenes 72,74, and 77 and gave enantioselectivities of over 92% (Scheme 8) [45,46]. The... 

Limbach PA, Crain PF, McCloskey JA. Summary the modified nucleosides of RNA. Nucleic Acids Res. 1994 22 2183-2196. Rozenski J, Crain PF, McCloskey JA. The RNA modification database 1999 update. Nucleic Acids Res. 1999 27 196-197. Beaucage SL, Iyer RP. The synthesis of modified oligonucleotides by the phosphoramidite approach and their applications. Tetrahedron 1993 49 6123-6194. 

A phosphoramidite monomer derived from (71) has been introduced into ODNs for post-synthesis modification. The ketone was treated with a number of aminooxy derivatives, and it was shown that the modification had little effect on duplex stability. This may be used to decorate DNA for a number of DNA applications. A series of modified dUTP analogues (72) which can incorporate a variety of amine derivatives, including biotinylated and fluorescent derivatives, has been prepared for study in PCR reactions. It was found that KOD Dash DNA polymerase was able to incorporate the modified triphosphates during PCR whilst other conventional DNA polymerases would not. 

Stereodefined oligo(ribonucleoside phosphorothioate)s were available only by the enzymatic method [51 -54] or by partially stereocontrolled H-phosphonate procedure [55,56]. However, both procedures could provide only products with RP configuration. Alternatively, compounds containing the single phosphorothioate modification were synthesized by nonstereospecific phosphoramidite or H-phosphonate methods and then separated into diastereomers by tedious HPLC procedure with various degree of success [57-59]. Such constructs became important tools for investigation of the mechanism of action of ri-bozymes. 

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