Synthesis of 1′#,2′,3′,4′#,5′,5″-2H6-β-D-ribonucleosides and 1′#, 2′,2″,3′,4′#,5′,5″-2H7-β-D-2′-deoxyribonucleosides for selective suppression of proton resonances in partially-deuterated oligo-DNA, oligo-RNA and in 2,5A core (1H-NMR window)
(1992) In Tetrahedron 48(41). p.9033-9072- Abstract
- Raney nickel-2H2O exchange reaction on an epimeric mixture of methyl α/β-D-ribofuranoside [α/β = ∼3:10]1 produced methyl 1#,2,3,4#,5,5′-2H6-α/β-ribofuranoside 2 [97 atom % 2H at C2, C3, C5/5′; ∼85 atom % 2H at C4 (C4#); ∼20 atom % 2H at C1(C1#)] which was obtained in 60 – 80 % yield along with epimeric xylo and arabino by-products. Toluoylation of the crude 2 in dry pyridine and a careful separation on a column of silica gel gave pure 1-O-methyl-2,3,5-tri-O-(4-toluoyl)-α/β-D-1#,2,3,4#,5,5′-2H6-ribofuranoside 4 (48%). Conversion of 4 to 1-O-acetyl-2,3,5-tri-O-toluoyl-α/β-D-1#,2,3,4#,5,5′-2H6-ribofuranoside 6 (82%) provided the crucial building block for the synthesis of deuterionucleosides for RNA or DNA synthesis. Compound 6 was then... (More)
- Raney nickel-2H2O exchange reaction on an epimeric mixture of methyl α/β-D-ribofuranoside [α/β = ∼3:10]1 produced methyl 1#,2,3,4#,5,5′-2H6-α/β-ribofuranoside 2 [97 atom % 2H at C2, C3, C5/5′; ∼85 atom % 2H at C4 (C4#); ∼20 atom % 2H at C1(C1#)] which was obtained in 60 – 80 % yield along with epimeric xylo and arabino by-products. Toluoylation of the crude 2 in dry pyridine and a careful separation on a column of silica gel gave pure 1-O-methyl-2,3,5-tri-O-(4-toluoyl)-α/β-D-1#,2,3,4#,5,5′-2H6-ribofuranoside 4 (48%). Conversion of 4 to 1-O-acetyl-2,3,5-tri-O-toluoyl-α/β-D-1#,2,3,4#,5,5′-2H6-ribofuranoside 6 (82%) provided the crucial building block for the synthesis of deuterionucleosides for RNA or DNA synthesis. Compound 6 was then condensed with silylateduracil, N4-benzoylcytosine, N6-benzoyladenine, N2-acetyl-O6-diphenylcarbamoylguanine and thymine in anhydrous solvent using trimethylsilyl trifluoromethanesulfonate to give the corresponding isomerically pure 1′#,2′,3′,4′#,5′,5″-2H6-ribonucleoside derivatives 7, 8, 9, 10, 11 in 75, 85, 60, 73 and 91% yields, respectively. 1′#,2′,3′,4′#,5′,5″-2H6-ribonucleosides 13 – 16 were converted in high yields to the corresponding 1′#,2′,2″,3′,4′#,5′,5″-2H7-2′-deoxynucleosides 41 – 44 in the following manner: 3′,5′-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl (TPDS))-1′#,2′,3′,4#′,5′,5″-2H6-nucleosides 29 – 32 were converted to the corresponding 2′-O-phenoxythiocarbonyl derivatives 33 – 36, which were deoxygenated by tri-n-butyltin deuteride to give 1′#,2′,2″,3′,4′#,5′,5″-2H7-2′-deoxynucleosides 37 – 40 and subsequently deprotected to give 41 – 44. Pure 1′#,2′,3′,4′#,5′,5″-2H6-ribonucleoside derivatives 12 – 15, 1′#,2′,2″,3′,4′#,5′,5″-2H7-2′-deoxynucleoside blocks 41 – 44 and their natural-abundance counterparts were then used to assemble partially deuterated ribonucleotide-dimers (* indicates deuterated moiety): UpA* 77, CpG* 78, ApU* 79, GpC* 80, partially deuterated 2′-deoxyribonucleotide-dimers d(TpA*) 93, d(ApT*) 95, d(GpC*) 96 and partially deuterated 2,5A core (A*2′p5′A2′p5′A*) (109). These nine partially deuterated oligonucleotides were subsequently compared with their corresponding natural-abundance counterparts by 500 MHz 1H-NMR spectroscopy to evaluate the actual NMR simplifications achieved in the non-deuterated part (1H-NMR window) as a result of specific deuterium incorporation. Detailed 1D 1H-NMR (500 MHz), 2D correlation spectra (DQF-COSY & TOCSY), T1 measurements for 1H-, 13C- and INEPT 13C-NMR spectra have been presented and discussed to assess the utility of stereospecific deuterium incorporation create the 1H- or 13C-NMR window. (Less)
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- author
- Földesi, András ; Nilson, Frans Peder R. LU ; Glemarec, Corine ; Gioeli, Carlo and Chattopadhyaya, Jyoti
- publishing date
- 1992-08-03
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Tetrahedron
- volume
- 48
- issue
- 41
- pages
- 40 pages
- publisher
- Elsevier
- external identifiers
-
- scopus:0026705840
- ISSN
- 0040-4020
- DOI
- 10.1016/S0040-4020(01)82001-9
- language
- English
- LU publication?
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- 6d6174bc-a734-47b2-ae0b-2c59d0e8fca1
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@article{6d6174bc-a734-47b2-ae0b-2c59d0e8fca1,
abstract = {{Raney nickel-2H2O exchange reaction on an epimeric mixture of methyl α/β-D-ribofuranoside [α/β = ∼3:10]1 produced methyl 1#,2,3,4#,5,5′-2H6-α/β-ribofuranoside 2 [97 atom % 2H at C2, C3, C5/5′; ∼85 atom % 2H at C4 (C4#); ∼20 atom % 2H at C1(C1#)] which was obtained in 60 – 80 % yield along with epimeric xylo and arabino by-products. Toluoylation of the crude 2 in dry pyridine and a careful separation on a column of silica gel gave pure 1-O-methyl-2,3,5-tri-O-(4-toluoyl)-α/β-D-1#,2,3,4#,5,5′-2H6-ribofuranoside 4 (48%). Conversion of 4 to 1-O-acetyl-2,3,5-tri-O-toluoyl-α/β-D-1#,2,3,4#,5,5′-2H6-ribofuranoside 6 (82%) provided the crucial building block for the synthesis of deuterionucleosides for RNA or DNA synthesis. Compound 6 was then condensed with silylateduracil, N4-benzoylcytosine, N6-benzoyladenine, N2-acetyl-O6-diphenylcarbamoylguanine and thymine in anhydrous solvent using trimethylsilyl trifluoromethanesulfonate to give the corresponding isomerically pure 1′#,2′,3′,4′#,5′,5″-2H6-ribonucleoside derivatives 7, 8, 9, 10, 11 in 75, 85, 60, 73 and 91% yields, respectively. 1′#,2′,3′,4′#,5′,5″-2H6-ribonucleosides 13 – 16 were converted in high yields to the corresponding 1′#,2′,2″,3′,4′#,5′,5″-2H7-2′-deoxynucleosides 41 – 44 in the following manner: 3′,5′-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl (TPDS))-1′#,2′,3′,4#′,5′,5″-2H6-nucleosides 29 – 32 were converted to the corresponding 2′-O-phenoxythiocarbonyl derivatives 33 – 36, which were deoxygenated by tri-n-butyltin deuteride to give 1′#,2′,2″,3′,4′#,5′,5″-2H7-2′-deoxynucleosides 37 – 40 and subsequently deprotected to give 41 – 44. Pure 1′#,2′,3′,4′#,5′,5″-2H6-ribonucleoside derivatives 12 – 15, 1′#,2′,2″,3′,4′#,5′,5″-2H7-2′-deoxynucleoside blocks 41 – 44 and their natural-abundance counterparts were then used to assemble partially deuterated ribonucleotide-dimers (* indicates deuterated moiety): UpA* 77, CpG* 78, ApU* 79, GpC* 80, partially deuterated 2′-deoxyribonucleotide-dimers d(TpA*) 93, d(ApT*) 95, d(GpC*) 96 and partially deuterated 2,5A core (A*2′p5′A2′p5′A*) (109). These nine partially deuterated oligonucleotides were subsequently compared with their corresponding natural-abundance counterparts by 500 MHz 1H-NMR spectroscopy to evaluate the actual NMR simplifications achieved in the non-deuterated part (1H-NMR window) as a result of specific deuterium incorporation. Detailed 1D 1H-NMR (500 MHz), 2D correlation spectra (DQF-COSY & TOCSY), T1 measurements for 1H-, 13C- and INEPT 13C-NMR spectra have been presented and discussed to assess the utility of stereospecific deuterium incorporation create the 1H- or 13C-NMR window.}},
author = {{Földesi, András and Nilson, Frans Peder R. and Glemarec, Corine and Gioeli, Carlo and Chattopadhyaya, Jyoti}},
issn = {{0040-4020}},
language = {{eng}},
month = {{08}},
number = {{41}},
pages = {{9033--9072}},
publisher = {{Elsevier}},
series = {{Tetrahedron}},
title = {{Synthesis of 1′#,2′,3′,4′#,5′,5″-2H6-β-D-ribonucleosides and 1′#, 2′,2″,3′,4′#,5′,5″-2H7-β-D-2′-deoxyribonucleosides for selective suppression of proton resonances in partially-deuterated oligo-DNA, oligo-RNA and in 2,5A core (1H-NMR window)}},
url = {{http://dx.doi.org/10.1016/S0040-4020(01)82001-9}},
doi = {{10.1016/S0040-4020(01)82001-9}},
volume = {{48}},
year = {{1992}},
}