Universal linker phosphoramidite

Abstract

Universal Linker phosphoramidite was synthesized and employed for conversion of conventional nucleoside bound solid phase into the universal support. The latter was successfully tested in preparation of the 20mer oligonucleotide.

New Cleavable Spacers for Tandem Synthesis of Multiple Oligo­nucleotides

“…The residue was purified by silica gel column chromatography (hexane/ EtOAc = 1/2) to give CS-2 (48.9 mg, 50%) as a colorless foam. (14) Under an argon atmosphere, DIPEA (0.303 mL, 1.77 mmol) and 2-(1Hbenzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) (336 mg, 0.886 mmol), 13 (244 mg, 0.886 mmol) were added to a solution of compound 12 (300 mg 0.443 mmol) in DMSO (5 mL). The reaction mixture was stirred at room temperature for 20 h. The resulting mixture was diluted with EtOAc.…”

“…Because TOPS reagents require relatively harsh conditions (40% methylamine/28% NH3 aq., 60 °C, overnight) for complete release of the ONs, a new cleavable spacer with enhanced reactivity is required. Universal linker derivatives, [13][14][15][16][17][18] which have been widely used for the synthesis of 3´-modified ONs in automated ON synthesis, would be applicable; therefore, we focused on a 1-(2,3-dihydroxypropyl)urea derivative 13,14 (commercially available as "Universal Support III" from Glen Research, Figure 2 left) and 7-oxabicyclo[2.2.1]heptane-2,3-diol derivatives 17,18 ("Glen UnySupport" or "UnyLinker" from Glen Research, Figure 2 right) as these can be efficiently cleaved under milder conditions. Based on these units, cleavable spacers (CSs) were designed as phosphoramidite monomers for the tandem synthesis of multiple ONs (Scheme 1, CS-1-4).…”

Solid‐Phase Supports for Oligonucleotide Synthesis

“…Solid supports 27a and 27f afforded yields very similar to those obtained from 18, while 27c bearing acetyl protection gave only 4% yield. It was also found later that the low stability of the formyl protecting group did not provide a reasonable shelf life (Yagodkin and Azhayev, 2009).…”

“…Various versions of these solid supports were used for the preparation of sugar- (Willams et al, 2009) and base-modified oligonucleotides (Seio et al, 2009(Seio et al, , 2012. The same core structure was also used for preparation of a universal phosphoramidite building block 20 that allows one to convert any solid support possessing a hydroxy group to the universal support (Yagodkin and Azhayev, 2009).…”