D4T Analogues with a Spacer
1635
Ja,b = 4.92 Hz, Ja,b = 3.75 Hz, Ja,a = 13.98 Hz, Ha), 3.89 (ddd, 1H, Jb,a = 4.92 Hz,
Jb,a = 3.84 Hz, Jb,b = 10.56 Hz, Hb), 3.76 (m, 1H, Hb), 3.61 (ddd, 1H, Ja,b = 7.8 Hz,
Ja,b = 3.84 Hz, Ja,a = 13.98 Hz, Ha), ose: 6.22 (dt, 1H, J3’,2’ = 5.97 Hz, J3’,1’ = 1.16 Hz,
J3’,4’ = 1.16 Hz, H3’), 5.92 (ddd, 1H, J2’,1’ = 1.04 Hz, J2’,3’ = 5.97 Hz, J2’,4’ = 2 Hz, H2’),
5.76 (br d, 1H, J1’,2’ = 1.04 Hz, H1’), 5.02 (m, 1H, H4’), 4.52 (dd, 1H, J5’,4’ = 3.64 Hz,
J5’,5’ = 11.72 Hz, H5’), 4.31 (dd, 1H, J5’,4’ = 5.4 Hz, J5’,5’ = 11.72 Hz, H5’), benzoyl
group: 8.05 (dd, 2H), 7.57 (tt, 1H), 7.45 (br t, 2H).
1-(4-(2’,3’-didehydro-2’,3’-dideoxy-b-D-ribofuranosyloxy)butyl)-thymine (7a).
Compound 6a (20 mg, 0.05 mmol) was stirred with methanolic ammonia (7 N)
(2 mL) in methanol (5 mL) at room temperature during 3 days. The solvent was
removed under reduced pressure and the crude residue was purified by thin layer
preparative chromatography on silica gel (CH2Cl2/EtOH) to yield compound 7a as a
viscous oil in 75% (11 mg). Rf = 0.51 (CH2Cl2/MeOH, 9/1, v/v); IR: 3160 (NH),
3020 (CH ar.), 2825–2950 (CH alkyl), 1690 (C O Thym), 1597 (C C), 1272 (C–
1
O–C). H NMR (400.13 MHz, CDCl3): thymine: d 8.91 (s, 1H, NH), 7.01 (d, 1H,
J6,CH3 = 0.9 Hz, H6), 1.91 (d, 3H, JCH3,6 = 1 Hz, C–CH3), N-alkyl: 3.86 (dt, 1H,
Ja,b = 6.16 Hz, Ja,a = 9.6 Hz, Ha), 3.72 (t, 2H, Jd,g = 7.24 Hz, Hd), 3.6 (dt, 1H,
Ja,b = 6.12 Hz, Ja,a = 9.6 Hz, Ha), 1.7 (m, 2H, Hb or Hg), 1.58 (m, 2H, Hb or Hg),
ose: 6.10 (dt, 1H, J3’,2’ = 5.8 Hz, J3’,4’ = 1.4 Hz, J3’,1’ = 1.4 Hz, H3’), 5.89 (dt, 1H,
J2’,3’ = 5.8 Hz, J2’,4’ = 1.4 Hz, J2’,1’ = 1.4 Hz, H2’), 5.73 (d, 1H, J1’,2’ = 1.4 Hz, H1’),
4.93 (m, 1H, H4’), 3.77 (dd, 1H, J5’,4’ = 2.8 Hz, J5’,5’ = 11.8 Hz, H5’), 3.57 (dd, 1H,
J5’,4’ = 3.4 Hz, J5’,5’ = 11.8 Hz, H5’).
1-(3-(2’,3’-didehydro-2’,3’-dideoxy-b-D-ribofuranosyloxy)propyl)-thymine (7b).
Compound 7b was prepared according to the procedure described for 7a starting from
6b (40 mg, 0.102 mmol) and stirred with methanolic ammonia (7 N) (1 mL). Yield:
22
90% (26 mg); [a]D = À41.6; (0.12; CH2Cl2); Rf = 0.49 (CH2Cl2/MeOH, 9/1, v/v);
IR: 3190 (NH), 3026 (CH ar.), 2832–2951 (CH alkyl), 1684 (C O Thym), 1604
1
(C C), 1270 (C–O–C). H NMR (400.13 MHz, CDCl3): thymine: d 9 (s, 1H, NH),
7.07 (d, 1H, J6,CH3 = 0.86 Hz, H6), 1.91 (d, 3H, JCH3,6 = 0.86 Hz, C–CH3), N-alkyl:
3.68–3.84 (m, 3H, Hg and Ha), 3.58 (dt, 1H, Ja,b = 5.68 Hz, Ja,a = 10.4 Hz, Ha), 1.89
(m, 2H, Hb), ose: 6.13 (dt, 1H, J3’,2’ = 5.96 Hz, J3’,1’ = 1.36 Hz J3’,4’ = 1.36 Hz, H3’),
5.89 (ddd, 1H, J2’,1’ = 0.68 Hz, J2’,3’ = 5.96 Hz, J2’,4’ = 1.6 Hz, H2’), 5.74 (br d, 1H,
J1’,2’ = 0.68 Hz, H1’), 4.93 (m, 1H, H4’), 3.79 (dd, 1H, J5’,4’ = 3.2 Hz, J5’,5’ = 11.7 Hz,
H5’), 3.61 (dd, 1H, J5’,4’ = 3 Hz, J5’,5’ = 11.7 Hz, H5’).
1-(2-(2’,3’-dehydro-2’,3’-dideoxy-b-D-ribofuranosyloxy)ethyl)-thymine (7c).
Compound 7c was prepared according to the procedure described for 7a starting from
6c (84 mg, 0.226 mmol) and stirred with methanolic ammonia (7 N) (2 mL). Yield:
22
74% (45 mg); [a]D = +11.98; (0.13; CH2Cl2); Rf = 0.47 (CH2Cl2/MeOH, 9/1, v/v);
IR: 3186 (NH), 3021 (CH ar.), 2830–2949 (CH alkyl), 1682 (C O Thym), 1606
1
(C C), 1272 (C–O–C). H NMR (400.13 MHz, CDCl3): thymine: d 9.05 (s, 1H, NH),
7.09 (d, 1H, J6,CH3 = 1.1 Hz, H6), 1.9 (d, 3H, JCH3,6 = 1.1 Hz, C–CH3), N-alkyl: 3.68–
3.84 (m, 3H, Hb and Ha), 3.58 (dt, 1H, Ja,b = 5.68 Hz, Ja,a = 10.4 Hz, Ha), ose: 6.13
(dt, 1H, J3’,2’ = 5.94 Hz, J3’,1’ = 1.28 Hz J3’,4’ = 1.28 Hz, H3’), 5.89 (ddd, 1H,
J2’,1’ = 0.96 Hz, J2’,3’ = 5.94 Hz, J2’,4’ = 1.54 Hz, H2’), 5.76 (br d, 1H, J1’,2’ = 0.96