Synthesis of Oligoribonucleotides by the H-Phosphonate Approach Using Base Labile 2′-O-Protecting Groups. V. Recent Progress in Development of the Method

Expanding functionality of RNA: synthesis and properties of RNA containing imidazole modified tandem G–U wobble base pairs

“…For 7 and 7i, where imidazole caused the smallest changes in t m , DG and Dn W (Table 1), the CD spectra were also similar. Thus, our results suggest that the imidazole modification may fit best in the structurally more flexible G-U motifs, such as 59-CGUG (7), which has only one hydrogen bond per G?U base pair according to the NMR structure. 10a However, more studies are certainly needed to confirm the generality of this observation.…”

“…Selective benzoylation of the 29-OH in 4 was immediately followed by phosphonylation of the 39-OH in the same reaction mixture following our previously published procedures. 7,8 Isomerically pure 29-O-(2-chlorobenzoyl)-39-O-(H-phosphonate) 5 was obtained after silica gel column chromatography. (1:9), 278 uC, 45 min; (d) imidazole, PCl 3 , NEt 3 , CH 2 Cl 2 , 278 uC, 1 h, 63% (two steps). To test our hypothesis that the imidazole heterocycle can be engineered in the major groove of the non-canonical tandem G-U wobble base pairs (Fig.…”

“…(1:9), 278 uC, 45 min; (d) imidazole, PCl 3 , NEt 3 , CH 2 Cl 2 , 278 uC, 1 h, 63% (two steps). To test our hypothesis that the imidazole heterocycle can be engineered in the major groove of the non-canonical tandem G-U wobble base pairs (Fig. 1) we prepared the self complementary sequences 6i-9i (Table 1) using standard H-phosphonate oligoribonucleotide procedures [7][8][9] and the imidazole modified monomer 5. The average coupling yields (typically .90% per step) were similar for 5 and the unmodified H-phosphonates.…”

Carbohydrate Chemistry for RNA Interference: Synthesis and Properties of RNA Analogues Modified in Sugar-Phosphate Backbone

“…Besides using asymmetric small molecule chemistry to access the modified carbohydrate, another innovative feature of our synthesis is that it minimizes late stage protecting group manipulations by keeping the base labile 2'-O-and N-acyl groups in the final products 51. Such an approach was encouraged by our previous successful experience with base labile protecting groups in the synthesis of natural [118,119] and modified [95,111] RNA. Thus, only selective deprotection of the primary tert-butyldiphenylsilyl (TBDPS) ether and oxidation of the alcohol are needed to complete the total synthesis of all four nucleoside azido acids (51) in 9-10 steps and 15-19% overall yields [115b].…”

Reactions at Oxygen Atoms

“…The above procedure has been utilized in oligoribonucleotide synthesis [278] using ribonucleosides with a base-labile 2'-O-(2-chlorobenzoyl) group.…”