An improved method for the preparation of the phosphoramidites of modified 2'-deoxynucleotides: Incorporation of 8-oxo-2'-deoxy-7h-guanosine into synthetic oligomers

Nucleosides and Nucleotides

Volumn 10, Issue 4, 1991, Pages 755-761

  Bodepudi, Veeraiah ^a   Iden, Charles R ^a   Johnson, Francis ^a  

^a STONY BROOK UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2' DEOXYNUCLEOTIDE; PHOSPHORAMIDIC ACID DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL MODIFICATION; DNA MODIFICATION; SYNTHESIS;

EID: 0025797517     PISSN: 07328311     EISSN: None     Source Type: Journal    
DOI: 10.1080/07328319108046660     Document Type: Article

References (28)

1. Strictly speaking these compounds should be named as purine nucleoside derivatives. However, for convenience in referring to them we have elected to use the 8-oxo-2'-deoxy-7H-guanosine terminology.
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14. Compound 6, like many of the 5'-O-DMT-2'-deoxynucleosides that we have synthesized appears to retain water tenaciously (perhaps as a partial hydrate) and needs rigorous drying before phosphoramidite preparation is attempted.
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20. By 31P NMR analysis, the most significant contaminant appears to be a hydrolysis product of the phosphite reagent.
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22. Satisfactory physical data were obtained for all new substances described in this paper. Data for representative products are as follows. (4). TLC (CH2Cl2/MeOH 4:1): Rf 0.72; m.p. 220° C; UV (MeOH): 293, 258; 1H NMR (300 MHz, DMSO-d6) δ 12.03 (1H, NH, s), 11.52 (1H, NH, s), 7.52 - 7.31 (5H, aryl, m), 6.17 (1H, H-C(1'), t, J = 7.05 Hz), 5.48 (2H, -CH2-Ph, s), 5.20 (1H, HO-C(3'), d, J = 3.90 Hz), 4.70 (1H, HO-C(5'), t, J = 5.55 Hz), 4.26 (1H, H-C(3'), m), 3.72 (1H, H-C(4'), m), 3.44 - 3.38 (2H, H-C(5'), m), 2.90 (1H, H-C(2'), m), 2.76 (1H, -CH-CO-N, m), 2.06 (1H, H-C(2'), m), 1.12 (6H, C-(Me)2, d, J = 6.90 Hz). 13C NMR (75 MHz, DMSO-d6) δ 180.67, 154.56, 153.29, 148.43, 147.84, 136.35, 129.31, 129.22, 129.07, 115.79, 88.20, 82.57, 71.98, 71.58, 62.78, 36.88, 35.53, 19.69. FAB/MS (+ ve ion, thioglycerol matrix): m/z 444 [(M + H)+, 7%], 328 [(Heterocyclic base + 2H)+, 9%], 274 (17%), 232 (51%), 181 (44%). (5). TLC (CH2Cl2/MeOH 4:1): Rf 0.56; m.p. 230° C (dec.); UV (MeOH): 301, 265; 1H NMR (300 MHz, DMSO-d6) 6 12.14 (1H, NH, s), 11.59 (1H, NH, s), 11.28 (1H, NH, s), 6.09 (1H, H-C(1'), t, J = 6.60 Hz), 5.17 (1H, HO-C(3'), d, J = 2.40 Hz), 4.73 (1H, HO-C(5'), m), 4.37 (1H, H-C(3'), m), 3.75 (1H, H-C(4'), m), 3.59 - 3.44 (2H, H-C(5'), m), 3.07 (1H, H-C(2), m), 2.74 (1H, -CH-CO-N, m), 1.98 (1H, H-C(2), m), 1.11 (6H, C-(Me)2, d, J = 8.10 Hz). FAB/MS (+ve ion, thioglycerol matrix): m/z 354 [(M + H)+, 8%], 238 [(Heterocyclic base + 2H)+, 15%]. (6). TLC (CH2Cl2/MeOH 4:1): Rf 0.78; m.p. 164 - 166° C; UV (MeOH): 302, 265, 201; 1H NMR (300 MHz, DMSO-d6) δ 12.13 (1H, NH, s), 11.43 (1H, NH, s), 11.24 (1H, NH, s), 7.34 - 6.76 (13H, aryl, m), 6.14 (1H, H-C(1'), t, J = 6.05 Hz), 5.16 (1H, HO-C(3'), d, J = 4.50 Hz), 4.44 (1H, H-C(3'), m), 3.91 (1H, H-C(4'), m), 3.72 and 3.71 (6H, OCH3, 2s), 3.32 and 3.06 (2H, H-C(5'), 2m), 2.98 (1H, H-C(2'), m), 2.74 (1H, -CH-CO-N, m), 2.12 (1H, H-C(2'), m), 1.12 (6H, C-(Me)2, d, J = 6.60 Hz). FAB/MS (-ve ion, thioglycerol matrix): m/z 654 [(M-H)-, 100%], 584 (28%), 352 (12%), 236 [(Heterocyclic base-H)-, 30%]. (7). TLC (CH2Cl2/MeOH 8:1): Rf 0.73; 1H NMR (300 MHz, CDC13): two diastereomers, 6 11.75 -11.13 (3H, 3NH, br s), 7.34 - 6.73 (13H, aryl, m), 6.12 (1H, H-C(1'), 2t, two diastereomers), 4.61 (1H, H-C(3'), m), 4.03 (3H, H-C(4') and -O-CH2-C, m), 3.71 (6H, OCH3, s), 3.45 (2H, -N-CH(iPr)2, m), 3.34 - 3.92 (2H, H-C(5'), m), 2.76 (2H, -CH2-CN, t, J = 6.0 Hz), 2.63 (1H, -CH-CO-N, m), 2.31 (2H, H-C(2'), m), 1.26 (12H, -CH3 of (iPr)2, dd), 1.15 (6H, -CO-C(Me)2, dd). 31P NMR (121 MHz, CDCl3) δ 146.63, 146.50 (two diastereomers). FAB/MS (-ve ion, thioglycerol matrix): m/z 854 [(M-H)-, 12%], 654 (14%, loss of phosphoramidite), 236 [(Heterocyclic base-H)-, 7%].
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