Pyridine → O6-Methyl-2'-deoxyguanosine

HRID 366968Notes

Reaction equation

HRID 366968 reaction equation
[C@@H:1]1([N:9]2[C:19]3[N:18]=[C:16]([NH2:17])[NH:15][C:13](=[O:14])[C:12]=3[N:11]=[CH:10]2)[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.N1C=C[CH:23]=[CH:22][CH:21]=1>>[CH:22]([O:14][C:13]1[C:12]2[N:11]=[CH:10][N:9]([C:19]=2[N:18]=[C:16]([NH2:17])[N:15]=1)[C@@H:1]1[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1)([CH3:23])[CH3:21].[CH3:21][O:14][C:13]1[C:12]2[N:11]=[CH:10][N:9]([C:19]=2[N:18]=[C:16]([NH2:17])[N:15]=1)[C@@H:1]1[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.[CH2:21]([O:14][C:13]1[C:12]2[N:11]=[CH:10][N:9]([C:19]=2[N:18]=[C:16]([NH2:17])[N:15]=1)[C@@H:1]1[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1)[CH3:22]

Participants

5

Reactant 2

HCID 1049PyridineHCID 135398592Deoxyguanosine

Product 3

HCID 73317O6-Methyl-2'-deoxyguanosineHCID 99549O6-EthyldeoxyguanosineHCID 158855Guanosine, 2'-deoxy-6-O-(1-methylethyl)-

Procedure

O6 -Methyldeoxyguanosine, O6 -ethyldeoxyguanosine and O6 -isopropyldeoxyguanosine are synthesized according to the published procedure of Fathi et al. (Tetrahedron Lett. 31:319-322, 1990). Trifluoroacetic anyhydride (2.3 mL, 16 mmol) is added to a cooled (0° C.) solution of 2'-deoxyguanosine (2 mmol, available from Sigma Chemical Company) in pyridine (10 mL). After 10 minutes, the appropriate alkoxide (4.3 g) in 300 mL of the appropriate alcohol (sodium methoxide in methanol for O6 -methyldeoxyguanosine, sodium ethoxide in ethanol for O6 -ethyldeoxyguanosine, sodium isopropoxide in isopropyl alcohol for O6 -isopropyldeoxyguanosine) is added dropwise and the reaction mixture is stirred for 24 hours (or 60 hours for the ethyl derivative and two days for the isopropyl derivative). The reaction is quenched with a solution of pyridinium hydrochloride (made from 12 mL pyridine and 4 mL of hydrochloric acid) and the excess acid destroyed with sodium bicarbonate (2 g). The mixture is then evaporated to dryness, resuspended in water and purified on a DYNAMAX (Rainin Instrument Co.) reversed-phase HPLC column using a gradient of 2-5% acetontrile in water over 45 minutes to yield O6 -methyldeoxyguanosine, O6 -ethyldeoxyguanosine or O6 -isopropyledeoxyguanosine, depending upon the particular alkoxide used above.

Workup

  1. additionTrifluoroacetic anyhydride (2.3 mL, 16 mmol) is added to
  2. customThe reaction is quenched with a solution of pyridinium hydrochloride (made from 12 mL pyridine and 4 mL of hydrochloric acid)
  3. customthe excess acid destroyed with sodium bicarbonate (2 g)
  4. customThe mixture is then evaporated to dryness
  5. custompurified on a DYNAMAX (Rainin Instrument Co.) reversed-phase HPLC column
  6. waitacetontrile in water over 45 minutes

Sources & evidence

ORD record
ord-d05f107f27694c96b45e344e42613af6
Source dataset
uspto-grants-2000_10
Patent number
US06132776

Reaction notes

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