PAPER
Regioselective N6-Alkylation of Adenosine
2487
1H NMR (DMSO-d6): d = 2.97 (br s, 3 H, Me), 3.55 (ddd,
J5¢b,5¢a = 12.0 Hz, J5¢b,4¢ = 3.6 Hz, J5¢b,OH = 7.0 Hz, 1 H, H5¢b), 3.67
(ddd, J5¢a,5¢b = 12.0 Hz, J5¢a,4¢ = 3.6 Hz, J5¢a,OH = 4.4 Hz, 1 H, H5¢a),
3.97 (ddd, J4¢,5¢b = 3.6 Hz, J4¢,5¢a = 3.6 Hz, J4¢,3¢ = 3.0 Hz, 1 H, H4¢),
4.15 (ddd, J3¢,4¢ = 3.0 Hz, J3¢,2¢ = 5.1 Hz, J3¢,OH = 4.7 Hz, 1 H, H3¢),
4.60 (ddd, J2¢,3¢ = 5.1 Hz, J2¢,1¢ = 6.1 Hz, J2¢,OH = 6.2 Hz, 1 H, H2¢),
5.15 (d, JOH,3¢ = 4.7 Hz, 1 H, 3¢-OH, exchangeable with D2O), 5.40
(dd, JOH,5¢b = 7.0 Hz, JOH,5¢a = 4.4 Hz, 1 H, 5¢-OH, exchangeable
with D2O), 5.40 (d, JOH,2¢ = 6.2 Hz, 1 H, 2¢-OH, exchangeable with
D2O), 5.88 (d, J1¢,2¢ = 6.1 Hz, 1 H, H1¢), 7.74 (br s, 1 H, NH, ex-
changeable with D2O), 8.22 (br s, 1 H, H2), 8.32 (s, 1 H, H8).
13C NMR (DMSO-d6): d = 27.09 (Me), 61.73 (C5¢), 70.70 (C3¢),
73.58 (C2¢), 85.96 (C4¢), 88.03 (C1¢), 119.88 (C5), 139.67 (C8),
148.09 (C4), 152.46 (C2), 155.19 (C6).
MS (APCI): m/z [M + H]+ calcd for C11H16N5O4: 282.12; found:
282.20; m/z [M – H– + HCOOH] calcd for C12H16N5O6: 326.11;
found: 326.22.
13C NMR (DMSO-d6): d = 29.36 (CH2N), 61.67 (C5¢), 70.65 (C3¢),
72.44 (HC≡), 73.64 (C2¢), 81.87 (-C≡), 85.92 (C4¢), 88.01 (C1¢),
119.91 (C5), 140.23 (C8), 148.86 (C4), 152.30 (C2), 154.05 (C6).
MS (APCI): m/z [M + H]+ calcd for C13H16N5O4: 306.12; found:
306.20; m/z [M – H– + HCOOH] calcd for C14H16N5O6: 350.11;
found: 350.14.
UV (H2O): lmax (log e) = 263 (4.310), pH 1; 264 (4.328), pH 7; 265
nm (4.306), pH 13.
N6-Furfuryladenosine (5d)
Method C gave 5d (251 mg, 63%) as a white powder; mp 150–155
°C (MeOH) [Lit.20 151–152 °C]; Rf = 0.33 (CH2Cl2–EtOH, 9:1).
1H NMR (DMSO-d6): 3.56 (ddd, J5¢b,5¢a = 12.0 Hz, J5¢b,4¢ = 3.9 Hz,
J5¢b,OH = 7.0 Hz, 1 H, H5¢b), 3.67 (ddd, J5¢a,5¢b = 12.0 Hz, J5¢a,4¢ = 3.9
Hz, J5¢a,OH = 4.6 Hz, 1 H, H5¢a), 3.97 (ddd, J4¢,5¢b = 3.9 Hz,
J4¢,5¢a = 3.9 Hz, J4¢,3¢ = 3.0 Hz, 1 H, H4¢), 4.15 (ddd, J3¢,4¢ = 3.0 Hz,
J
J
3¢,2¢ = 4.9 Hz, J3¢,OH = 4.8 Hz, 1 H, H3¢), 4.61 (ddd, J2¢,3¢ = 4.9 Hz,
2¢,1¢ = 6.2 Hz, J2¢,OH = 6.2 Hz, 1 H, H2¢), 4.72 (br s, 2 H, NCH2C),
UV (H2O): lmax (log e) = 262 (4.199), pH 1; 265 (4.174), pH 7; 265
nm (4.171), pH 13.
5.15 (d, JOH,3¢ = 4.8 Hz, 1 H, 3¢-OH, exchangeable with D2O), 5.34
(dd, JOH,5¢b = 7.0 Hz, JOH,5¢a = 4.6 Hz, 1 H, 5¢-OH, exchangeable
with D2O), 5.41 (d, JOH,2¢ = 6.2 Hz, 1 H, 2¢-OH, exchangeable with
D2O), 5.89 (d, J1¢,2¢ = 6.2 Hz, 1 H, H1¢), 6.23 (dd, J3,4 = 3.1 Hz,
J3,5 = 0.7 Hz, 1 H, H3Fur), 6.35 (dd, J4,3 = 3.1 Hz, J4,5 = 1.9 Hz, 1 H,
H4Fur), 6.52 (dd, J5,4 = 3.1 Hz, J4,3 = 1.9 Hz, 1 H, H5Fur), 8.23 (s, 1
H, H2), 8.23 (br s, 1 H, NH, exchangeable with D2O), 8.37 (s, 1 H,
H8).
N6-Benzyladenosine (5b)
Following the typical procedure for 5a using 4b (1.21 g, 2.3 mmol)
gave 5b (634 mg, 78%) as a white powder; mp 160–162 °C [Lit.18
167–168 °C]; Rf = 0.32 (CH2Cl2–EtOH, 9:1).
1H NMR (DMSO-d6): 3.55 (ddd, J5¢b,5¢a = 12.1 Hz, J5¢b,4¢ = 3.8 Hz,
J5¢b,OH = 7.1 Hz, 1 H, H5¢b), 3.67 (ddd, J5¢a,5¢b = 12.1 Hz, J5¢a,4¢ = 3.3
Hz, J5¢a,OH = 4.6 Hz, 1 H, H5¢a), 3.97 (ddd, J4¢,5¢b = 3.8 Hz,
J4¢,5¢a = 3.3 Hz, J4¢,3¢ = 2.8 Hz, 1 H, H4¢), 4.15 (ddd, J3¢,4¢ = 2.8 Hz,
13C NMR (DMSO-d6): d = 36.60 (CH2N), 61.66 (C5¢), 70.64 (C3¢),
73.56 (C2¢), 85.91 (C4¢), 87.99 (C1¢), 106.71 (Fur), 110.47 (Fur),
119.83 (C5), 140.00 (C8), 141.85 (Fur), 148.70 (C4), 152.27 (C2),
152.85 (Fur), 154.38 (C6).
J
J
3¢,2¢ = 5.1 Hz, J3¢,OH = 4.7 Hz, 1 H, H3¢), 4.61 (ddd, J2¢,3¢ = 5.1 Hz,
2¢,1¢ = 6.1 Hz, J2¢,OH = 6.2 Hz, 1 H, H2¢), 4.72 (br s, 2 H, OCH2Ph),
5.17 (d, JOH,3¢ = 4.7 Hz, 1 H, 3¢-OH, exchangeable with D2O), 5.38
(dd, JOH,5¢b = 7.1 Hz, JOH,5¢a = 4.6 Hz, 1 H, 5¢-OH, exchangeable
with D2O), 5.42 (d, JOH,2¢ = 6.2 Hz, 1 H, 2¢-OH, exchangeable with
D2O), 5.89 (d, J1¢,2¢ = 6.1 Hz, 1 H, H1¢), 7.17–7.37 (m, 5 H, HPh),
8.19 (br s, 1 H, H2), 8.36 (s, 1 H, H8), 8.37 (br s, 1 H, NH, ex-
changeable with D2O).
13C NMR (DMSO-d6): d = 42.97 (CH2N), 61.70 (C5¢), 70.68 (C3¢),
73.56 (C2¢), 85.94 (C4¢), 88.03 (C1¢), 119.76 (C5), 126.66 (Ph),
127.14 (Ph), 128.23 (Ph), 139.94 (C8), 148.42 (C4), 152.38 (C2),
154.60 (C6).
UV (H2O): lmax (log e) = 265 (4.259), pH 1; 267 (4.315), pH 7; 267
nm (4.263), pH 13.
N6-(3-Methylbut-2-enyl)adenosine (5e)
Method C; recrystallization (H2O) gave 5e (124 mg, 33%); mp 130–
132 °C (EtOH) [Lit.21 134–136 °C]; Rf = 0.45 (CH2Cl2–EtOH, 4:1).
1H NMR (DMSO-d6): 1.67 (s, 3 H, Me), 1.70 (s, 3 H, Me), 3.55
(ddd, J5¢b,5¢a = 12.1 Hz, J5¢b,4¢ = 3.0 Hz, J5¢b,OH = 7.9 Hz, 1 H, H5¢b),
3.67 (ddd, J5¢a,5¢b = 12.1 Hz, J5¢a,4¢ = 3.6 Hz, J5¢a,OH = 4.6 Hz, 1 H,
H5¢a), 3.96 (ddd, J4¢,5¢b = 3.0 Hz, J4¢,5¢a = 3.6 Hz, J4¢,3¢ = 2.8 Hz, 1 H,
H4¢), 4.14 (ddd, J3¢,4¢ = 2.8 Hz, J3¢,2¢ = 5.3 Hz, J3¢,OH = 4.8 Hz, 1 H,
H3¢), 4.08 (br s, 2 H, NCH2C), 4.60 (ddd, J2¢,3¢ = 5.3 Hz, J2¢,1¢ = 6.0
Hz, J2¢,OH = 6.2 Hz, 1 H, H2¢), 5.15 (d, JOH,3¢ = 4.8 Hz, 1 H, 3¢-OH,
exchangeable with D2O), 5.27–5.33 (m, 1 H, CCH=C), 5.39 (dd,
JOH,5¢b = 7.9 Hz, JOH,5¢a = 4.6 Hz, 1 H, 5¢-OH, exchangeable with
D2O), 5.40 (d, JOH,2¢ = 6.2 Hz, 1 H, 2¢-OH, exchangeable with D2O),
5.87 (d, J1¢,2¢ = 6.0 Hz, 1 H, H1¢), 7.82 (br s, 1 H, NH, exchangeable
with D2O), 8.19 (br s, 1 H, H2), 8.31 (s, 1 H, H8).
13C NMR (DMSO-d6): d = 18.49 (Me), 26.02 (Me), 38.57 (CH2N),
62.22 (C5¢), 71.20 (C3¢), 74.22 (C2¢), 86.57 (C4¢), 88.79 (C1¢),
120.14 (C5), 121.73 (CH=), 135.41 (=CMe2), 140.49 (C8), 148.63
(C4), 153.14 (C2), 154.93 (C6).
MS (APCI): m/z [M + H]+ calcd for C15H22N5O4: 336.17; found:
336.23; m/z [M – H– + HCOOH] calcd for C16H22N5O6: 380.16;
found: 380.20.
MS (APCI): m/z [M + H]+ calcd for C17H20N5O4: 358.15; found:
358.19; m/z [M – H– + HCOOH] calcd for C18H20N5O6: 402.14;
found: 402.19.
UV (H2O): lmax (log e) = 265 (4.314), pH 1; 268 (4.310), pH 7; 269
nm (4.324), pH 13.
N6-Prop-2-ynyladenosine (5c)
Method C; recrystallization (EtOH–H2O) gave 5c (145 mg, 41%);
mp 171–174 °C (EtOH–H2O) [Lit.19 169 °C]; Rf = 0.33 (CH2Cl2–
EtOH, 9:1).
1H NMR (DMSO-d6): 3.0 (t, J = 2.3 Hz, 1 H, HC≡C), 3.56 (ddd,
J5¢b,5¢a = 12.0 Hz, J5¢b,4¢ = 3.7 Hz, J5¢b,OH = 7.2 Hz, 1 H, H5¢b), 3.68
(ddd, J5¢a,5¢b = 12.0 Hz, J5¢a,4¢ = 3.9 Hz, J5¢a,OH = 4.3 Hz, 1 H, H5¢a),
3.97 (ddd, J4¢,5¢b = 3.7 Hz, J4¢,5¢a = 3.9 Hz, J4¢,3¢ = 2.8 Hz, 1 H, H4¢),
4.16 (ddd, J3¢,4¢ = 2.8 Hz, J3¢,2¢ = 5.0 Hz, J3¢,OH = 4.7 Hz, 1 H, H3¢),
4.29 (br s, 2 H, NCH2Ph), 4.60 (ddd, J2¢,3¢ = 5.0 Hz, J2¢,1¢ = 5.9 Hz,
J2¢,OH = 6.2 Hz, 1 H, H2¢), 5.15 (d, JOH,3¢ = 4.7 Hz, 1 H, 3¢-OH, ex-
changeable with D2O), 5.31 (dd, JOH,5¢b = 7.2 Hz, JOH,5¢a = 4.3 Hz, 1
H, 5¢-OH, exchangeable with D2O), 5.42 (d, JOH,2¢ = 6.2 Hz, 1 H, 2¢-
OH, exchangeable with D2O), 5.90 (d, J1¢,2¢ = 5.9 Hz, 1 H, H1¢), 8.16
(br s, 1 H, NH, exchangeable with D2O), 8.27 (br s, 1 H, H2), 8.39
(s, 1 H, H8).
UV (H2O): lmax (log e) = 264 (4.261), pH 1; 268 (4.263), pH 7; 268
nm (4.266), pH 13.
N6-(4-Hydroxybut-2-ynyl)adenosine (5f)
Method C gave 5f (234 mg, 61%) as a white powder; mp 160–162
°C (EtOH–H2O); Rf = 0.13 (CH2Cl2–EtOH, 9:1).
1H NMR (DMSO-d6): 3.56 (ddd, J5¢b,5¢a = 11.9 Hz, J5¢b,4¢ = 4.1 Hz,
J5¢b,OH = 7.0 Hz, 1 H, H5¢b), 3.68 (ddd, J5¢a,5¢b = 12.0 Hz, J5¢a,4¢ = 3.6
Synthesis 2011, No. 15, 2483–2489 © Thieme Stuttgart · New York