11348 J. Am. Chem. Soc., Vol. 118, No. 46, 1996
Robins et al.
f 95% EtOAc/hexanes) to give 20d (221 mg, 80%) as a slightly yellow
glass: UV max 259 nm (ꢀ 13 200), min 225 nm (ꢀ 1300); H NMR
2, H5′,5′′), 4.37 (m, 1, H4′), 6.07 (dd, J3′-4′ ) 3.7 Hz, 1, H3′), 6.39 (br
s, 2, NH2), 6.69 (d, 1, H1′), 7.11-7.50 (m, 5, Ph), 8.32 (s, 1, H2), 8.36
(s, 1, H8); MS (CI) m/z 548.1830 (100, MH+ [C24H34N5O4S2Si] )
548.1822).
1
(DMSO-d6) δ 0.02 and 0.04 (s and s, 3 and 3, Me2Si), 0.86 (s, 9, t-Bu),
3.25 (s, 3, CH3), 3.79 (dd, J5′′-5′ ) 11.5 Hz, J5′′-4′ ) 3.9 Hz, 1, H5′′)
3.90-4.05 (m, 2, H4′,5′), 4.61 (q, J ) 5.5 Hz, 1, H3′), 5.61 (dd, J2′-1′
) 3.9 Hz, J2′-3′ ) 5.1 Hz, 1, H2′), 5.95 (d, JOH3′-3′ ) 5.7 Hz, 1, OH3′),
6.25 (d, Hz, 1, H1′), 7.39 (br s, 2, NH2), 8.17 (s, 1, H2), 8.31 (s, 1,
H8); MS (CI) m/z 460.1689 (100, MH+ [C17H30N5O6SSi] ) 460.1686).
5′-O-(tert-Butyldimethylsilyl)-2′-O-(p-tolylsulfonyl)adenosine (20e).
Procedure E. TBDMSCl (447 mg, 2.9 mmol) was added to a
suspension of dried 19e (672 mg, 1.6 mmol) in dried pyridine (12 mL),
and stirring was continued overnight at ambient temperature. Volatiles
were evaporated, and the residue was partitioned (HCl/H2O//EtOAc).
The organic phase was washed (NaHCO3/H2O, brine), dried (Na2SO4),
and evaporated, and the residue was chromatographed (CH2Cl2 f 3.5%
MeOH/CH2Cl2) to give 20e (566 mg, 66%) as a white glass: UV max
261 nm (ꢀ 13 100), min 242 nm (ꢀ 7100); 1H NMR (DMSO-d6) δ 0.04
(s, 6, SiMe2), 0.88 (s, 9, t-Bu), 2.29 (s, 3, CH3), 3.74 (dd, J5′′-5′ ) 11.3
Hz, J5′′-4′ ) 4.3 Hz, 1, H5′′), 3.90 (dd, J5′-4′ ) 4.4 Hz, 1, H5′), 4.02-
4.08 (m, 1, H4′), 4.32-4.38 (m, 1, H3′), 5.51 (dd, J2′-1′ ) 6.6 Hz,
J2′-3′ ) 5.4 Hz, 1, H2′), 6.04 (d, 1, H1′), 6.07 (d, JOH3′-3′ ) 5.5 Hz, 1,
OH3′), 7.05 (d, J ) 8.2 Hz, 2, Harom), 7.34 (br s, 2, NH2), 7.43 (d, 2,
Analogous treatment (procedure G) of 20b gave 21b (40%).
Model Reactions with Bu3SnH/AIBN/Toluene/∆. Procedure
H.47-49 Individual samples (0.1 mmol) of nucleosides 17, 18, 20, 21,
23, 24, 26, and 27 were dissolved in dried toluene (4 mL; ∼25 mM
solutions) and deoxygenated (Ar, 45 min). Bu3SnH (54 µL, 58 mg,
0.2 mmol) was injected through the septum, and deoxygenation was
continued for 15 min. AIBN (5 mg, 0.03 mmol) was added, and the
solution was heated at gentle reflux (∼115 °C, oil bath) for 2.5 h under
Ar [some reactions were complete after ∼30 min (TLC)]. Volatiles
were evaporated, and the residue was chromatographed {CHCl3 f 5%
MeOH/CHCl3 [or EtOAc f 5% MeOH/EtOAc; or CHCl3 f MeOH/
Me2CO/CHCl3 (1:10:50); or EtOAc f 20% S1/EtOAc]} to give the
respective products (Tables 2 and 3).
Model Reactions with Ph3SiH/BzOOBz/Toluene/∆. Procedure
I.47,48 Individual samples (0.1 mmol) of nucleosides 17, 18, 20, 21,
23, 24, 26, and 27 were dissolved in dried toluene (4 mL, ∼25 mM
solutions) and deoxygenated (Ar, 45 min). Ph3SiH (78 mg, 0.3 mmol)
and BzOOBz (10 mg, 0.04 mmol) were added, and the solution was
heated at gentle reflux (∼115 °C, oil bath) for 3 h. [Second portions
of Ph3SiH (52 mg, 0.2 mmol) and BzOOBz (5 mg, 0.02 mmol) were
added and reflux was continued for 4 h in some cases.] Volatiles were
evaporated, and the residue was chromatographed as described in
procedure H to give the respective products (Tables 2 and 3).
3′-Deoxy-2′-O-(p-tolylsulfonyl)adenosine (37b). Compound 21e
(67 mg, 0.1 mmol) was treated by procedure H (1 h), the resulting 36b
(TLC, S5; quantitative after evaporation) was dissolved in THF (5 mL),
and TBAF/THF (1 M, 0.2 mL) was added. The solution was stirred
for 3 h at ambient temperature, and volatiles were evaporated in vacuo.
The residue was purified by preparative RP-HPLC (10 f 50% MeCN/
H2O; 2.8 mL/min, 100 min) to give white solid 37b (33 mg, 81%; tR
) 81 min): mp 110-115 °C (softening), 225-230 °C dec; UV max
262, 228 nm (ꢀ 17 600, 11 400), min 240 nm (ꢀ 7700); 1H NMR
H
arom), 8.02 (s, 1, H2), 8.07 (s, 1, H8); MS (CI) m/z 536.1986 (100,
MH+ [C23H34N5O6SSi] ) 536.1999).
Compounds 20b (procedure E, 88%), 23a (procedure D, 56%), 23b
(procedure C, 96%), and 23c (procedure D, 92%) were prepared
analogously to those described.
5′-O-(tert-Butyldimethylsilyl)-2′-chloro-2′-deoxy-3′-O-(phenoxy-
thiocarbonyl)adenosine (21a). Procedure F. DMAP (103 mg, 0.84
mmol) and PTCCl (70 µL, 86 mg, 0.50 mmol) were added to a
suspension of dried 20a (161 mg, 0.40 mmol) in dried MeCN (6 mL),
and stirring of the yellow solution was continued for 6 h at ambient
temperature. Volatiles were evaporated, and the residue was chro-
matographed [EtOAc/cyclohexanes (1:3) f MeOH/cyclohexane/EtOAc
(1:25:75)] to give 21a (206 mg, 95%) as an off-colored glass: mp
1
192-193 °C; UV max 257 nm (ꢀ 15 100), min 224 nm (ꢀ 5700); H
NMR δ 0.15 (s, 6, Me2Si), 0.95 (s, 9, t-Bu), 4.03 (m, 2, H5′,5′′), 4.58
(m, 1, H4′), 5.22 (dd, J2′-1′ ) 6.1 Hz, J2′-3′ ) 5.9 Hz, 1, H2′), 5.97 (m,
1, H3′), 6.32 (br s, 2, NH2), 6.40 (d, 1, H1′), 7.08-7.55 (m, 5, Ph),
8.16 (s, 1, H2), 8.39 (s, 1, H8); 13C NMR δ [-5.03, -4.81, 18.91,
26.45 (TBDMS)], 58.37 (C5′), 63.20 (C2′), 81.01 (C3′), 83.91 (C4′),
88.80 (C1′), 120.36 (C5), 139.04 (C8), 150.50 (C4), 153.43 (C2), 155.96
(C6), [122.16, 127.42, 130.19, 153.80, 194.34 (PTC)]; MS (CI) m/z
538.1511 {43, MH+ (C23H31[37Cl]N5O4SSi) ) 538.1525}, 536.1538
{100, MH+ (C23H31[35Cl]N5O4SSi) ) 536.1555}.
(DMSO-d6/D2O) δ 2.22-2.52 (m, 5, H3′,3′′, CH3), 3.44 (dd, J5′′-5′ )
12.3 Hz, J5′′-4′ ) 3.7 Hz, 1, H5′′), 3.63 (dd, J5′-4′ ) 3.0 Hz, 1, H5′),
4.31-4.39 (m, 1, H4′), 5.56 (ddd, J2′-3′′ ) 6.4 Hz, J2′-3′ ) 4.7 Hz,
J2′-1′ ) 4.0 Hz, 1, H2′), 6.02 (d, 1, H1′), 7.19 (d, J ) 8.5 Hz, 2, Harom),
7.55 (d, 2, Harom), 8.1 (s, 1, H2), 8.27 (s, 1, H8); MS (FAB) m/z 406
(100, MH+). Anal. Calcd for C17H19N5O5S‚H2O (423.4): C, 48.22;
H, 5.00; N, 16.54. Found: C, 48.51; H, 5.26; N, 16.60.
Acknowledgment. We thank the American Cancer Society
(DHP-34) and Brigham Young University development funds
for support and Mrs. Jeanny K. Gordon for assistance with the
manuscript.
Analogous treatment of 20c-e and 23a,c by procedure F gave 21c
(79%), 21d (60%), 21e (85%), 24a (65%), and 24c (63%), respectively.
9-[5-O-(tert-Butyldimethylsilyl)-2-S-methyl-3-O-(phenoxythiocar-
bonyl)-2-thio-â-D-arabinofuranosyl]adenine (24b). Procedure G.
DMAP (59 mg, 0.48 mmol) and PTCCl (42 µL, 54 mg, 0.31 mmol)
were added to a suspension of dried 23b (90 mg, 0.22 mmol) in cold
(5 °C), dried MeCN (3 mL) and pyridine (0.1 mL). After ∼15 min,
dried pyridine (0.5 mL), CH2Cl2 (1 mL), MeCN (10 mL), and PTCCl
(42 µL, 54 mg, 0.31 mmol) were added, and the resulting yellow
solution was stirred overnight at 5 °C. Volatiles were evaporated, the
residue was partitioned (NaHCO3/H2O//CHCl3), and the organic phase
was washed (H2O, brine), dried (Na2SO4), and evaporated. The residue
was chromatographed (CHCl3 f 3% MeOH/CHCl3) to give 24b (55
mg, 45%) as an off-white foam: UV max 259 nm (ꢀ 14 500), min 228
JA962117M
(47) Oven- or flame-dried glassware was flushed with argon prior to
use.
(48) Crude 5′-O-TBDMS mixtures were (a) dissolved in THF (3 mL)
and stirred for 6 h at ambient temperature with TBAF/THF (1 M; 0.25
mL) or (b) dissolved in MeOH (3 mL) and refluxed for 3 h with NH4F (15
equiv). These deprotection mixtures were evaporated, and the residues were
chromatographed [Dowex 1 × 2 (OH-); H2O f 40% MeOH/H2O) for 30b
and 35b; silica gel (EtOAc f 20% S1/EtOAc) for 32a] if necessary.
(49) Excess Bu3SnH was removed from products by extensive washing
of silica columns with EtOAc/pentane prior to elution of product(s) or by
vigorously stirring the residue with EtOAc/KF/H2O (5 mL/50 mg/0.5 mL)
for 16 h at ambient temperature (no 5′-desilylation observed) followed by
chromatography.
1
nm (ꢀ 7200); H NMR δ 0.15 (s, 6, Me2Si), 0.95 (s, 9, t-Bu), 1.90 (s,
3, SCH3), 3.91 (dd, J2′-1′ ) 5.5 Hz, J2′-3′ ) 3.8 Hz, 1, H2′), 4.05 (m,