A simple procedure for the preparation of protected 2′-O-methyl or 2′-O-ethyl ribonucleoside-3′-O-phosphoramidites

Abstract

Protected 2'-O-methyl and 2'-O-ethyl ribonucleoside-3'-O-phosphoramidites were prepared via alkylation of the ribonucleosides at an early stage in the synthesis. Utilizing a strategy of minimal protection, the alkylation was performed with unprotected cytidine and adenosine, or with O6-protected guanosine and N3,5'-O-protected uridine using methyl or ethyl iodide and sodium hydride. In subsequent steps, the introduction of standard protective groups for oligonucleotide synthesis and the concomitant separation from 3'-O-alkylated isomers was accomplished. A modification of the phosphitylation procedure permitted facile isolation of the desired phosphoramidites which show high coupling efficiencies in oligomer assembly.

Interaction of the Basic Protrusion ofEscherichia coliRibonuclease HI with its Substrate

“…For 2'-Omethylguanosine, an improved method reported by Wagner et al (1991) was used. The N-acyl-5'-O-(4,4'-dimethoxytrityl)-2'-O-methylnucleosides were treated dihedral angle space was performed using FEDER (Wako & Go, 1987).…”

Antisense oligonucleotides made of 2'‐O‐alkylRNA: their properties and applications in RNA biochemistry

“…The following alkyl groups have been incorporated: -CH, (methyl) [7,8], -CH,CH, (ethyl) [12,13], -CH,CH=CH, (ally]) [1,9,10], CH,CH,CH,CH, (butyl) [ll], or -…”

Synthesis, Structural, and Conformational Analysis of 4′‐C‐Alkyl‐2′‐O‐Ethyl‐Uridine Modified Nucleosides

“…Also, dual modifications at 2′‐ and 4′‐ sugar positions such as 4′‐ C ‐aminomethyl‐2′‐ O ‐methyl (4′‐AM‐2′‐OMe), 4′‐ C ‐aminoethyl‐2′‐ O ‐methyl (4′‐AMEt‐2′‐OMe), and 4′‐ C ‐aminopropyl‐2′‐ O ‐methyl (4′‐AMPr‐2′‐OMe) analogs have adopted C2′‐ endo (South , DNA ‐type) sugar conformation [21,22] . In contrast, other bi‐functional sugar modifications such as 4′‐ C ‐aminomethyl‐2′‐deoxy‐2′‐fluoro (4′‐AM‐2′‐F), 4′‐ C ‐aminoethyl‐2′‐deoxy‐2′‐fluoro (4′‐AMEt‐2′‐F), 2′,4′‐diF, 2′‐OMe‐4′‐F, 2′‐F‐4′‐OMe, 2′,4′‐diOMe, 2′‐F‐4′‐OMe‐araU, 2′,4′‐diF‐araU tuned the sugar conformation predominantly toward C3′‐ endo ( North , RNA ‐type), which has been attributed to the small size, high electronegativity of fluorine, and additional C−H⋅⋅⋅F interactions [23–30] . From the above observations, it is clear that 2′ and 4′‐ modifications can alter the sugar conformation, structural stability, and functional role of the duplex.…”