7380 J . Org. Chem., Vol. 63, No. 21, 1998
Robins et al.
An analogous oxidation of 3a (0.057 g, 0.1 mmol) with Oxone
(0.20 g, 0.325 mmol) replacing NaIO4 gave colorless crystalline
5a (0.035 g, 60%).
10 200), min 225, 263 nm (ꢀ 6900, 5800); MS m/z 501 (20, M+),
165 (100, BH). Anal. Calcd for C27H31N5O3Si: C, 64.64; H,
6.23; N, 13.96. Found: C, 64.80; H, 6.07; N, 13.57.
2-Am in o-9-[5-O-(ter t-bu tyldiph en ylsilyl)-2,3-O-su lfon yl-
â-D-r ibofu r a n osyl]-6-m eth oxyp u r in e (5b). Oxidation of 3b
(0.30 g, 0.52 mmol) by procedure A gave 5b (0.265 g, 86%) as
a gray solid. Chromatography and crystallization (procedure
A) gave 5b (mp 95-97 °C): UV max 249, 282 nm (ꢀ 10 700,
9100), min 230, 263 nm (ꢀ 3700, 5500); MS m/z 597 (20, M+),
540 (100, M - 57). Anal. Calcd for C27H31N5O7SSi: C, 54.26;
H, 5.23; N, 11.72. Found: C, 54.36; H, 5.46; N, 11.49.
5′-O-Acetyl-2′,3′-O-su lfon yla d en osin e (6a ). Oxidation of
4a (0.355 g, 1 mmol) by procedure A gave 6a (0.308 g, 83%) as
gray crystals. Chromatography (procedure A) and crystalliza-
tion (EtOAc) gave 6a (mp 208-210 °C dec): UV max 258 nm
(ꢀ 15 000), min 225 nm (ꢀ 1800); MS m/z 371 (10, M+), 164
(100), 135 (24, BH). Anal. Calcd for C12H13N5O7S‚0.3EtOAc:
C, 39.96; H, 3.66; N, 17.65. Found: C, 40.14; H, 4.02; N, 17.32.
9-(5-O-Acetyl-2,3-O-su lfon yl-â-D-r ibofu r an osyl)-2-am in o-
6-m eth oxyp u r in e (6b). Oxidation of 4b (0.32 g, 0.83 mmol)
by procedure A gave 6b (0.30 g, 90%) as a gray solid.
Chromatography and crystallization (procedure A) gave 6b
(mp 148-150 °C): UV max 249, 282 nm (ꢀ 10 700, 9000), min
225, 264 nm (ꢀ 3000, 5400); MS m/z 401 (50, M+), 165 (44,
BH), 83 (100). Anal. Calcd for C13H15N5O8S: C, 38.90; H, 3.77;
N, 17.45. Found: C, 39.12; H, 3.87; N, 17.18.
9-[5-O-(ter t-Bu tyldiph en ylsilyl)-2,3-dideoxy-â-D-glycer o-
p en t-2-en ofu r a n osyl]h yp oxa n th in e (8c). Treatment of 11c
(0.13 g, 0.17 mmol) by procedure B and crystallization (EtOAc)
gave 8c (29 mg). Chromatography of the mother liquor (1%
MeOH/EtOAc) and crystallization (EtOAc) gave additional 8c
(48 mg, 79% total, mp 89-91 °C): UV max 250 nm (ꢀ 14 900),
min 233 nm (ꢀ 6500); MS m/z 415 (10, M - 57), 136 (100, BH).
Anal. Calcd for C26H28N4O3Si‚0.5EtOAc: C, 65.09; H, 6.24;
N, 10.84. Found: C, 64.91; H, 6.55; N, 10.84.
Parallel treatment of the crude mesylate mixture (11c/
trimesylate ∼3:1, 0.136 g, ∼0.20 mmol) gave colorless crystal-
line 8c (78 mg, 76%) with identical physical and spectral
properties.
P r oced u r e C. 9-(2,3-Did eoxy-â-D-glycer o-p en t-2-en o-
fu r a n osyl)a d en in e (9a ). Meth od A. TBAF/THF (1 M, 0.32
mL, 0.32 mmol) was added to a solution of 8a (0.15 g, 0.318
mmol) in THF (5 mL) and was stirred for 2 h at ambient
temperature. Volatiles were evaporated, and the residue was
dissolved (H2O) and chromatographed [Dowex 1 × 2 (OH-),
H2O] to give colorless crystalline 9a (0.068 g, 92%, mp 194-
195 °C, lit.9 mp 188-190 °C): UV max 259 nm (ꢀ 13 200), min
226 nm (ꢀ 1900); MS m/z 233 (10, M+), 135 (100, BH).
Treatment of 8a (0.12 g, 0.254 mmol) with NH4F (0.10 g,
2.7 mmol) in MeOH (10 mL) for 5 h at 60 °C gave 9a (0.052 g,
88%) after purification [Dowex 1 × 2 (OH-), H2O].
2′,3′-O-Su lfin yla d en osin e (7a ). SOF221 was distilled (-20
°C) into a low-pressure jar cooled at -70 °C. Cold (-20 °C)
MeCN (20 mL) and adenosine (1a ; 0.267 g, 1 mmol) were
added slowly, the jar was sealed, and the contents were stirred
for 24 h at ambient temperature. The mixture was cooled (ice/
H2O), H2O (10 mL) was added, and the solution was concen-
trated (∼10 mL) in vacuo. EtOAc (30 mL) was added with
cooling (ice/H2O), and the solution was neutralized (to pH 5.0-
5.5, solid NaHCO3). The organic layer was separated, and the
aqueous phase was extracted (EtOAc, 3 × 20 mL). The
combined organic phase was washed [cold NaHCO3/H2O (20
mL), H2O (20 mL), and brine (20 mL)] and dried (Na2SO4),
and volatiles were evaporated to give 7a (0.225 g, 72%, exo/
endo ∼2:1) as a white solid. A sample was recrystallized
(EtOAc/hexanes) to give 7a (mp 198-200 °C dec): UV max
259 nm (ꢀ 14 300), min 226 nm (ꢀ 1900); MS m/z 313 (40, M+),
164 (100), 135 (90, BH). Anal. Calcd for C10H11N5O5S: C,
38.34; H, 3.54; N, 22.35. Found: C, 38.12; H, 3.74; N, 22.13.
2-Am in o-6-m eth oxy-9-(2,3-O-su lfin yl-â-D-r ibofu r an osyl)-
p u r in e (7b). Treatment of 1b23a (0.295 g, 1 mmol) with SOF2
as described for 7a [with addition of pyridine (0.16 mL, 2
mmol) to the reaction mixture] gave 7b (0.314 g, 92%, exo/
endo ∼2:1). A sample was diffusion crystallized (EtOAc/
hexanes) to give 7b (mp 188-189 °C): UV max 250, 282 nm
(ꢀ 10 200, 9000), min 225, 263 nm (ꢀ 3400, 5000); MS m/z 343
(80, M+), 165 (100, BH). Anal. Calcd for C11H13N5O6S: C,
38.48; H, 3.82; N, 20.40. Found: C, 38.26; H, 3.93; N, 20.16.
P r oced u r e B. 9-[5-O-(ter t-Bu t yld ip h en ylsilyl)-2,3-d i-
d eoxy-â-D-glycer o-p en t-2-en ofu r a n osyl]a d en in e (8a ). So-
dium naphthalenide35 in dried THF (0.5 M) was added slowly
(double-ended cannula) to a stirred solution of 5a (0.120 g, 0.21
mmol) in dried, deoxygenated (Ar, 30 min) THF (8 mL) at -50
°C (under Ar) until the green color of the radical anion
persisted [TLC (S2) after 5 min indicated complete conversion
of 5a to a more polar product]. Saturated NH4Cl/H2O was
added (pH 5.5-6.5), volatiles were evaporated in vacuo, and
EtOAc (20 mL) and H2O (10 mL) were added. The aqueous
phase was extracted [EtOAc (15 mL)], and the combined
organic phase was dried (Na2SO4). Volatiles were evaporated,
and the residue was chromatographed (1% MeOH/CHCl3) to
give colorless 8a (0.058 g, 59%, mp 154-156 °C, lit.9 mp 155-
157 °C): UV max 260 nm; MS m/z 471 (2, M+), 414 (100, M -
57).
Meth od B. Treatment of 6a (0.185 g, 0.5 mmol) by
procedure B (to the point of evaporation of volatiles) gave a
more polar product [TLC (S1)]. Et2O (20 mL) and H2O (10 mL)
were added, and the organic layer was extracted (H2O, 5 mL).
The combined aqueous phase was concentrated and chromato-
graphed [Dowex 1 × 2 (OH-), H2O]. The white solid was
diffusion crystallized (MeOH/Et2O) to give 9a (0.056 g, 48%).
Meth od C. NaH (0.06 g, 1.25 mmol, 50% dispersion in
mineral oil) was washed (dried THF, 3 × 5 mL) and suspended
in dried THF (10 mL) under argon. A solution of 2a (0.2 g,
0.4 mmol) in dried THF (10 mL) was added and was stirred
at ambient temperature until evolution of H2 ceased.
A
solution of ethyl dichlorophosphate (0.048 mL, 0.065 g, 0.4
mmol) in dried THF (5 mL) was added dropwise, and after 1
h, TLC (S1) indicated conversion of almost all starting material
to a less polar product. The reaction mixture was cooled (-50
°C) and subjected to procedure B, and a more polar product
was formed [TLC (S1)]. Saturated NH4Cl/H2O was added,
volatiles were evaporated in vacuo, and EtOAc (20 mL) and
H2O (10 mL) were added. The aqueous layer was extracted
(EtOAc, 10 mL), and the combined organic phase was dried
(Na2SO4). Volatiles were evaporated, and the residue was
dissolved (THF, 10 mL). The mixture was deprotected and
chromatographed (procedure C) to give colorless crystalline 9a
(0.025 g, 27%). Further elution of the Dowex 1 × 2 (OH-)
column with MeOH gave 1a (0.013 g, 12%).
Meth od D. Treatment of 11a (0.13 g, 0.20 mmol) by
procedure B (-50 °C, ∼10 min) and crude 8a by procedure C
[aqueous layer washed (Et2O) before purification on the Dowex
column)] gave 9a (0.036 g, 79%, mp 194-195 °C): UV max
259 nm (ꢀ 13 400), min 226 nm (ꢀ 2000).
Meth od E. Treatment of 5′-O-tosyladenosine34 (0.505 g, 1.2
mmol) by procedure D [back-extraction of the combined
aqueous layers (CHCl3, 3×), no column chromatography] and
crystallization (MeOH) gave 13a (415 mg, 60%, mp 163-166
°C dec): 1H NMR δ 2.36 (s, 3, Me), 3.30, 3.40 (2 × s, 2 × 3, 2
× Ms), 4.46-4.59 (m, 3, H4′,5′,5′′), 5.72 (dd, J 3′-4′ ) 4.0 Hz,
J 3′-2′ ) 5.3 Hz, 1, H3′), 6.10 (t, J ) 5.1 Hz, 1, H2′), 6.29 (d,
J 1′-2′ ) 4.9 Hz, 1, H1′), 7.31 (d, J ) 8.0 Hz, 2, arom), 7.45 (br
s, 2, NH2), 7.68 (d, J ) 8.0 Hz, 2, arom), 8.05 (s, 1, H2), 8.26
(s, 1, H8); HRMS (CI) m/z 578.0693 (60, MH+ [C19H24N5O10S3]
) 578.0685). Treatment of 13a (0.072 g, 0.125 mmol) by
procedure B (as modified in method B) gave 9a (0.016 g, 55%).
2-Am in o-9-(2,3-d id eoxy-â-D-glycer o-p en t-2-en ofu r a n o-
syl)-6-m eth oxyp u r in e (9b). Meth od A. Treatment of 6b
(0.12 g, 0.3 mmol) by procedure B and workup [as described
for 9a (method B)] gave 9b (0.048 g, 61%) as a white solid
2-Am in o-9-[5-O-(ter t-b u t yld ip h en ylsilyl)-2,3-d id eoxy-
â-D-glycer o-p en t-2-en ofu r a n osyl]-6-m eth oxyp u r in e (8b).
Treatment of 5b (0.13 g, 0.22 mmol) by procedure B gave solid
8b (46 mg, 42%). A sample was purified [RP-HPLC: C18
column, H2O/MeCN (70:30 f 0:100), 120 min (tR 110 min)] to
give 8b (mp 75-80 °C): UV max 249, 281 nm (ꢀ 11 100,