428
Vol. 56, No. 4
1
9.43.
MeOH, 100/0→95/05, v/v), to give 8 (367 mg, 75%) as a white foam. H-
NMR (DMSO-d6) d (ppm): 0.96 (s, 9H, tBut–Si); 2.30—2.39 (m, 1H, H2ꢁ);
2.77—2.86 (m, 1H, H2ꢇ); 3.73 (part of ABX system, 1H, JA-Bꢃ10.2 Hz,
1
6: Yield 30%; white foam. H-NMR (DMSO-d6) d (ppm): 0.86 and 0.93
(s, 18H, 2ꢈtBut–Si); 3.72—3.64 (m, 1H, H5ꢁ); 3.82—3.85 (m, 1H, H5ꢇ);
4.13—4.25 (m, 2H, H4ꢁ, H3ꢁ); 4.80—4.90 (m, 1H, H2ꢁ); 5.46 (d, 1H,
Jꢃ6.1 Hz, OH3ꢁ); 6.10 (d, 1H, Jꢃ6.0 Hz, H1ꢁ); 7.05—7.62 (m, 22H,
4ꢈPh–Si and NH2); 7.93 (s, 1H, H2); 7.96 (s, 1H, H8). MALDI-TOF MS
m/z: 745.6 Da [MꢂH]; 767.4 Da [MꢂNa]ꢂ; 783.0 Da [MꢂK]ꢂ; Anal. Calcd
for C42H49N5O4Si2: C, 67.80; H, 6.64; N, 9.41. Found: C, 67.90; H, 6.63; N,
9.42.
JA-Xꢃ4.6 Hz, H5ꢁ); 3.87—4.00 (m, 2H, H5ꢇ, H4ꢁ); 4.50—4.60 (m, 1H, H3ꢁ);
5.42 (d, 1H, Jꢃ4.2 Hz, OH3ꢁ); 6.37 (t, 1H, Jꢃ13.0 Hz, H1ꢁ); 7.30—7.61 (m,
12H, 4ꢈPh–Si and NH2); 8.08 (s, 1H, H2); 8.25 (s, 1H, H8). MALDI-TOF
MS m/z: 490.8 Da [MꢂH]; 512.7 Da [MꢂNa]ꢂ; 528 Da [MꢂK]ꢂ; Anal.
Calcd for C26H31N5O3Si: C, 63.78; H, 6.38; N, 14.30. Found: C, 63.50; H,
6.38; N, 14.30.
3ꢀ,5ꢀ-Bis-O-(tert-butyldiphenylsilyl)-2ꢀ-deoxyadenosine (7) Com-
pound 7 was obtained as described for compounds 5 and 6 starting from de-
oxyadenosine. The crude product was purified by silica gel column chro-
matography (eluent: CH2Cl2/MeOH, 100/0→97/3, v/v) to afford compound
5ꢀ-O-(tert-Butyldimethylsilyl)adenosine (15) The crude product was
purified by silica gel column chromatography (eluent: CH2Cl2/MeOH,
100/0→95/05, v/v), to give 15 (316 mg, 83%) as a white solid (mp 178—
180 °C).30)
1
7 (426 mg, 59%) as a white foam. H-NMR (DMSO-d6) d (ppm): 0.82 and
9-[5ꢀ-O-(tert-Butyldimethylsilyl)-b-D-arabinofuranosyl]adenine (18)
The crude product was purified by silica gel column chromatography (elu-
ent: CH2Cl2/MeOH, 100/0→90/10, v/v), to give 18 (282 mg, 74%) as a
1.05 (s, 18H, 2ꢈtBut–Si); 2.35—2.40 (m, 1H, H2ꢁ); 2.73—2.81 (m, 1H,
H2ꢁ); 3.40—3.50 (m, 1H, H5ꢁ); 3.66 (part of ABX system, 1H, JA-Bꢃ
11.2 Hz, JB-Xꢃ4.8 Hz, H5ꢇ); 4.09—4.12 (m, 1H, H4ꢁ); 4.68—4.72 (m, 1H,
H3ꢁ); 6.43 (t, 1H, Jꢃ6.5 Hz, H1ꢁ); 7.29—7.64 (m, 22H, 4ꢈPh–Si and NH2);
8.00 (s, 1H, H2); 8.13 (s, 1H, H8). MALDI-TOF MS m/z: 729.5 Da [MꢂH];
789.5 Da [MꢂNaꢂK]ꢂ; Anal. Calcd for C42H49N5O3Si2: C, 69.29; H, 6.78;
N, 9.62. Found: C, 69.27; H, 6.75; N, 9.61.
1
white solid (mp 157—158 °C). H-NMR (DMSO-d6) d (ppm): 0.83 (s, 6H,
2ꢈMe–Si); 1.00 (s, 9H, tBut–Si); 3.72—3.81 (m, 3H, H5ꢁ, H5ꢇ, H4ꢁ);
4.06—4.16 (m, 2H, H3ꢁ, H2ꢁ); 5.51 (d, 1H, Jꢃ4.5 Hz, OH3ꢁ); 5.61 (d, 1H,
Jꢃ5.0 Hz, OH2ꢁ); 6.19 (d, 1H, Jꢃ5.0 Hz, H1ꢁ); 7.21 (br s, 2H, NH2); 8.07
(s, 1H, H2); 8.07 (s, 1H, H8). MALDI-TOF MS m/z: 382.4 Da [MꢂH];
404.2 Da [MꢂNa]ꢂ; Anal. Calcd for C16H27N5O4Si: C, 50.37; H, 7.13; N,
18.36. Found: C, 50.38; H, 7.10; N, 18.35.
Preparation of N6-tert-Butyldimethylsilyl-3ꢀ,5ꢀ-bis-O-(tert-butyldi-
methylsilyl)-2ꢀ-deoxyadenosine and 3ꢀ,5ꢀ-Bis-O-(tert-butyldimethylsilyl)-
2ꢀ-deoxyadenosine (9, 10) Compounds 9 and 10 were prepared following
the synthetic strategy described for compounds 5 and 6 starting form de-
oxyadenosine and TBDMSCl. The crude mixture was purified by silica gel
column chromatography (eluent: Hexane/EtOAc, 95/05→70/30, v/v), to give
compounds 9 and 10.
9-[5ꢀ-O-(tert-Butyldiphenylsilyl)-b-D-arabinofuranosyl]adenine (21)
The crude product was purified by silica gel column chromatography (elu-
ent: CH2Cl2/MeOH, 100/0→90/10, v/v), to give 21 (383 mg, 76%) as a
white solid (mp 89—93 °C).29)
9-[5ꢀ-O-(Methyldiphenylsilyl)-b-D-arabinofuranosyl]adenine (25)
The crude product was purified by silica gel column chromatography (elu-
ent: CH2Cl2/MeOH, 100/0→90/10, v/v), to give 25 (372 mg, 78%) as a
9: Yield 4%; white oil. 1H-NMR (DMSO-d6) d (ppm): ꢅ0.06, ꢅ0.01,
0.00, 0.01, 0.11 and 0.31 (s, 18H, 6ꢈMe–Si); 0.83, 0.84 and 0.96 (s, 27H,
3ꢈtBut–Si); 2.26—2.32 (m, 1H, H2ꢁ); 2.86—3.00 (m, 1H, H2ꢇ); 3.60—3.70
(m, 1H, H5ꢁ); 3.76—3.84 (m, 2H, H5ꢇ, H4ꢁ); 4.60—4.68 (m, 1H, H3ꢁ);
6.30—6.37 (m, 2H, H1ꢁ, 6-NH); 8.21 (s, 1H, H2); 8.32 (s, 1H, H8).
MALDI-TOF MS m/z: 595.5 Da [MꢂH]; 617.4 Da [MꢂNa]ꢂ; 633.5 Da
[MꢂK]ꢂ; Anal. Calcd for C28H55N5O3Si3: C, 56.61; H, 9.33; N, 11.79.
Found: C, 56.68; H, 9.33; N, 11.75.
1
white solid (mp 168—172 °C). H-NMR (DMSO-d6) d (ppm): 0.62 (s, 3H,
Me–Si); 3.86—3.90 (m, 3H, H5ꢁ, H5ꢇ, H4ꢁ); 4.17—4.20 (m, 2H, H3ꢁ, H2ꢁ);
5.61 (d, 1H, Jꢃ3.8 Hz, OH3ꢁ); 5.69 (d, 1H, Jꢃ4.5 Hz, OH2ꢁ); 6.27 (d, 1H,
Jꢃ4.1 Hz, H1ꢁ); 7.24—7.56 (m, 12H, 2ꢈPh–Si and NH2); 8.06 (s, 1H, H2);
8.13 (s, 1H, H8). MALDI-TOF MS m/z: 464.8 Da [MꢂH]; 486.7 Da
[MꢂNa]ꢂ; 502.1 Da [MꢂK]ꢂ; Anal. Calcd for C23H25N5O4Si: C, 59.59; H,
5.44; N, 15.11. Found: C, 59.58; H, 5.43; N, 15.11.
10: Yield 70%; white solid (mp 125—128 °C).31)
3ꢀ,5ꢀ-Bis-O-(tert-butyldimethylsilyl)adenosine and 2ꢀ,5ꢀ-Bis-O-(tert-
butyldimethylsilyl)adenosine (13, 14) Compounds 13 and 14 were ob-
tained as described for compounds 5 and 6. The crude mixture purified by
silica gel column chromatography (eluent: CH2Cl2/MeOH, 100/0→95/05,
v/v), gave pure compounds 13, 14.
General Synthetic Procedure for the Preparation of TIPDS Deriva-
tives (11, 12, 35, 36) 3ꢁ,5ꢁ-O-TIPDS derivatives of adenosine, 2ꢁ-de-
oxyadenosine or araA were obtained by treatment of the dry nucleoside
(1 mmol), suspended in pyridine (10 ml), with 1,3-dichloro-1,1,3,3-tetraiso-
propyldisiloxane (TIPDSCl2) (1 mmol), following a synthetic procedure pre-
viously described.34) Starting from araA, by a one-step reaction, both 35 and
36 were obtained. The crude products were purified by silica gel column
chromatography (eluent: CH2Cl2/MeOH, 100/0→97/03, v/v).
13: Yield 36%; white solid (mp 202—204 °C).32)
14: Yield 19%; white solid (mp 174—177 °C).32)
Preparation of 9-(3ꢀ,5ꢀ-Bis-O-TBDPS), 9-(2ꢀ,5ꢀ-Bis-O-TBDPS) and
9-(2ꢀ,3ꢀ,5ꢀ-Tri-O-TBDPS-b-D-arabinofuranosyl)adenine (22, 23, 24)
Compounds 22—24 were prepared by a one step reaction starting form araA
and TBDPSCl following the synthetic strategy previously reported for the
preparation of compounds 5 and 6. The crude mixture was purified by silica
gel column chromatography (eluent: CH2Cl2/MeOH, 98/2→97/3, v/v), to
give pure compounds 22—24.
3ꢀ,5ꢀ-O-(1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl)adenosine (11)
Yield 80%; white foam.35)
3ꢀ,5ꢀ-O-(1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl)-2ꢀ-deoxyadenosine
(12) Yield 81%; white foam.36)
9-[5ꢀ-O-(1-Hydroxy-1,1,3,3-tetraisopropyl-disiloxanyl)-b-D-arabinofu-
ranosyl]adenine (35) Yield 15%; white solid (mp 160—165 °C). 1H-
NMR (DMSO-d6) d (ppm): 0.76—1.11 (m, 28H, TIPDS); 3.80—3.83 (m,
1H, H5ꢁ); 3.95—3.96 (m, 2H, H5ꢇ, H4ꢁ); 4.15—4.25 (m, 2H, H3ꢁ, H2ꢁ);
5.55 (d, 1H, Jꢃ4.3 Hz, OH3ꢁ); 5.65 (d, 1H, Jꢃ3.9 Hz, OH2ꢁ); 6.08 (s, 1H,
Si–OH); 6.25 (d, 1H, Jꢃ4.1 Hz, H1ꢁ); 7.25 (br s, 2H, NH2); 8.08 (s, 1H,
H2); 8.12 (s, 1H, H8). MALDI-TOF MS m/z: 529.1 Da [MꢂH]; 551.1 Da
[MꢂNa]ꢂ; 566.3 Da [MꢂK]ꢂ; Anal. Calcd for C22H41N5O6Si2: C, 50.07; H,
7.83; N, 13.27. Found: C, 49.93; H, 7.81; N, 13.30.
22: Yield 12%; white solid (mp 219—225 °C). 1H-NMR (400 MHz,
DMSO-d6) d (ppm): 0.84 and 1.06 (s, 18H, 2ꢈtBut–Si); 3.47, 3.59 (part of
AB system, 2H, JA-Bꢃ10.8 Hz, JA-Xꢃ4.4 Hz, JB-Xꢃ6.8 Hz, H5ꢁ, H5ꢇ);
4.07—4.11 (m, 1H, H4ꢁ); 4.26—4.28 (m, 1H, H2ꢁ); 4.36—4.38 (m, 1H,
H3ꢁ); 5.78 (d, 1H, J ꢃ4.8 Hz, OH2ꢁ); 6.41 (d, 1H, Jꢃ4.0 Hz, H1ꢁ); 7.27—
7.64 (m, 22H, 4ꢈPh–Si and NH2); 7.91 (s, 1H, H2); 8.13 (s, 1H, H8).
MALDI-TOF MS m/z: 745.2 Da [MꢂH]; 767.4 Da [MꢂNa]ꢂ; 783.3 Da
[MꢂK]ꢂ; Anal. Calcd for C42H49N5O4Si2: C, 67.80; H, 6.64; N, 9.41. Found:
C, 67.91; H, 6.62; N, 9.42.
9-[3ꢀ,5ꢀ-O-(1,1,3,3-Tetraisopropyldisiloxane-1,3-diyl)-b-D-arabinofu-
ranosyl]adenine (36) Yield 57%; white foam.37)
23: Yield 10%; white foam. 1H-NMR (400 MHz, DMSO-d6) d (ppm):
0.80 and 1.03 (s, 18H, 2ꢈtBut–Si); 3.93—4.01 (m, 3H, H5ꢁ, H5ꢇ, H4ꢁ)
4.30—4.32 (m, 1H, H3ꢁ); 4.39—4.43 (m, 1H, H2ꢁ); 5.29 (d, 1H, Jꢃ5.2 Hz,
OH3ꢁ); 6.24 (d, 1H, Jꢃ4.8 Hz, H1ꢁ); 6.90 (s, 2H, NH2); 7.12—7.66 (m,
20H, 4ꢈPh–Si); 7.99 (s, 1H, H2); 8.08 (s, 1H, H8). MALDI-TOF MS m/z:
745.3 Da [MꢂH]; 767.1 Da [MꢂNa]ꢂ; 783.1 Da [MꢂK]ꢂ; Anal. Calcd for
C42H49N5O4Si2: C, 67.80; H, 6.64; N, 9.41. Found: C, 67.78; H, 6.63; N,
9.44.
3ꢀ,5ꢀ-Bis-O-(tert-butyldiphenylsilyl)adenosine and 2ꢀ,5ꢀ-Bis-O-(tert-
butyldiphenylsilyl) adenosine (5, 6) Bis-silylated compounds 5 and 6
were obtained by treatment of dry adenosine (1 mmol), dissolved in dry
DMF (1 ml), with imidazole (4.4 mmol) and tert-butyldiphenylsilyl chloride
(TBDPSCl) (2.2 mmol). The crude mixture was purified by silica gel column
chromatography (eluent: CH2Cl2/MeOH, 100/0→95/5, v/v) to give 297 mg
and 222 mg of compounds 5 and 6 respectively.
1
5: Yield 40%; white foam. H-NMR (DMSO-d6) d (ppm): 0.83 and 1.09
24: Yield 10%; white foam. 1H-NMR (400 MHz, DMSO-d6) d (ppm):
0.54, 0.92 and 0.94 (s, 27H, 3ꢈtBut–Si); 3.04 (A part of ABX system, 1H,
(s, 18H, 2ꢈtBut–Si); 3.21—3.29 (m, 1H, H5ꢁ); 3.50—3.63 (m, 1H, H5ꢇ);
3.99—4.02 (m, 1H, H4ꢁ); 4.48—4.51 (m, 1H, H3ꢁ); 4.75—4.78 (m, 1H,
H2ꢁ); 5.72 (d, 1H, Jꢃ6.6 Hz, OH2ꢁ); 6.05 (d, 1H, Jꢃ6.6 Hz, H1ꢁ); 7.29—
7.73 (m, 24H, 4ꢈPh–Si, NH2, H2, H8). MALDI-TOF MS m/z: 745.6 Da
[MꢂH]; 767.4 Da [MꢂNa]ꢂ; 783.0 Da [MꢂK]ꢂ; Anal. Calcd for
C42H49N5O4Si2: C, 67.82; H, 6.64; N, 9.41. Found: C, 67.82; H, 6.62; N,
JA-Bꢃ10.8 Hz, JA-Xꢃ4.0 Hz, H5ꢁ); 3.67—3.72 (m, 1H, H5ꢇ); 3.88 (s, 1H,
H3ꢁ); 4.26 (part of ABX system, 1H, JX-Bꢃ8.4 Hz, JX-Aꢃ4.0 Hz, H4ꢁ); 4.31
(d, 1H, J2ꢁ-1ꢁꢃ2.8 Hz, H2ꢁ); 6.49 (d, 1H, J1ꢁ-2ꢁꢃ2.8 Hz, H1ꢁ); 6.82 (d, 2H,
Jꢃ7.2 Hz, NH2); 6.96—8.00 (m, 30H, 6ꢈPh–Si); 7.96 (s, 1H, H2); 8.17 (s,