Synthesis of 5′-Terminal Capped Oligonucleotides Using O–N Phosphoryl Migration of Phosphoramidite Derivatives

Abstract

Trivalent phosphoramidite derivatives could be readily converted by reacting with 1-hydroxy-7-azabenzotriazole to phosphotriester intermediates; these intermediates reacted smoothly with phosphorylated compounds to give pyrophosphate derivatives. This new phosphorylation approach enabled a facile and rapid synthesis of 5'-adenylated DNA oligomers (A(5')ppDNA) on resins using a silyl-type linker. Our new approach could be applied to the synthesis of a 2'-OMe-RNA oligomer containing the 5'-terminal 2,2,7-trimethylguanosine cap structure.

Towards novel efficient and stable nuclear import signals: synthesis and properties of trimethylguanosine cap analogs modified within the 5′,5′-triphosphate bridge

“…Chemical syntheses P1-(N 2 ,N 2 ,N 7 -trimethylguanosine-5′-yl)-P3-guanosin-5′-yl triphosphate m 3 2,2,7 GpppG (1 N 2 ,N 2 ,N 7 -Trimethylguanosine 5′-diphosphate imidazolide m 3 2,2,7 GDP-Im (16 GpNHp (25). To compound 23 (DMGpNHp, 150 mg, 0.25 mmol) dissolved in DMSO (3.7 mL), CH 3 I was added (196 μL, 3.14 mmol) and the mixture was stirred for 12 h at RT.…”

“…D1: 1 H NMR δ H (400 MHz, D 2 O, TSP), 3.17 (6H, s), 4.05 (3H, s), 4.24-4.36 (4H, m), 4.36-4.40 (1H, m), 4.42-4.44 (1H, m), 4.46 (1H, dd, J 5.0, 5.3), 4.49 (1H, dd, J 3.7, 5.1), 4.60 (1H, dd, J 3.4, 5.3), 4.62 (1H, dd, J 5.1, 6.1), 5.78 (1H, d, J 6.1), 5.96 (1H, d, J 3.4), 7.98 (1H, s), 8.98 (1H, s)*; *slowly exchanging in D 2 O. 31 -GpNHp (25). To compound 23 (DMGpNHp, 150 mg, 0.25 mmol) dissolved in DMSO (3.7 mL), CH 3 I was added (196 μL, 3.14 mmol) and the mixture was stirred for 12 h at RT.…”

Metallophyte wastes and polymetallic catalysis: a promising combination in green chemistry. The illustrative synthesis of 5′-capped RNA

“…Indeed only short 29-OMe RNA bearing a 7m cap were reported. 18,24 Finally, with P. douarrei extract, the capping reaction was not as efficient as with N. caerulescens since the desired compound was present at 7% only in the reaction mixture.…”

New Deoxyribozymes for the Native Ligation of RNA

“…5 -AppRNA is the active intermediate during RNA ligation by protein enzymes (such as T4 RNA ligase), which activate the 5 -phosphate of the RNA donor by adenylation with ATP, and upon reaction with the 3 -OH of the acceptor RNA, AMP is released as a leaving group [23]. A number of convenient routes for the synthesis of 5 -adenylated oligonucleotides have been reported [24][25][26], and these were previously used as donor substrates for in vitro selections of catalytic DNA. Several deoxyribozymes are known to form 2 ,5 -branched nucleic acid architectures with 5 -adenylated RNA and DNA [27,28].…”