8142 J . Org. Chem., Vol. 63, No. 23, 1998
J ung and Kiankarimi
) 10.8 Hz, H5), 3.32 (1H, dd, J ) 10.6, 10.4 Hz, H1ax), 3.01
(3H, s), 2.30 (1H, br dm, J ) 15.6 Hz), 1.84 (1H, br dm, J )
13.7 Hz), 1.65-1.76 (1H, m), 1.38-1.50 (1H, m), 0.87 (9H, s),
0.04 (6H, s). 13C NMR (100 MHz, CDCl3) δ: 77.67, 75.06,
69.35, 65.72, 38.52, 29.97, 26.95, 25.92, 18.40, -5.29, -5.34.
FT-IR (neat): 2955.3, 2930.2, 2856.9, 1356.0, 1176.7, 1108.4
cm-1. MS (EI) m/z (rel intensity) 325.2 ([M + H]+, 2), 229.2
(37), 171.1 (100). High-resolution EI MS (m/z): 325.1505, calcd
(11.8 mg, 0.032 mmol) in tetrahydrofuran (1.5 mL) was added
tetrabutylammonium fluoride (38 mg, 0.038 mmol) on silica
gel. The suspension was stirred at room temperature for 24
h. The mixture was filtered through a plug of cotton and flash
chromatographed (10% methanol in CHCl3) to give the desired
alcohol 7a as a white film (7.6 mg, 95%). 1H NMR (400 MHz,
CD3OD) δ: 8.57 (1H, s), 8.18 (1H, s), 4.65 (1H, br s), 4.38 (1H,
d, J ) 12.8 Hz), 4.07 (1H, dd, J ) 12.8, 2.6 Hz), 3.55-3.63
(3H, m), 2.16-2.19 (2H, m), 1.37-1.54 (2H, m), 1.26 (1H, br
s). 13C NMR (100 MHz, CDCl3) δ: 155.76, 152.05, 148.99,
140.77, 78.07, 68.73, 64.46, 48.98, 26.83, 21.45 (one low-field
carbon not resolved). FT-IR (neat): 3283.3, 3140.5, 2926.4,
2855.0, 1606.9, 1462.2, 1306.0, 1055.2 cm-1. MS (EI) m/z (rel
intensity) 250.1 ([M + H]+, 41), 143.2 (93), 136.1 (100). High-
resolution EI MS (m/z): 249.1225, calcd for C11H15N5O2
for C13H29O5SSi ([M + H]+) 325.1505. [R]25 ) -9.6 (c ) 0.4,
D
CH2Cl2).
1,5-An h yd r o-3,4-d id eoxy-6-O-[(1,1-d im et h yl)et h yld i-
m eth yl]silyl-D-th r eo-h exitol (23). Applying the above pro-
cedure to the syn diacetate 21a (413 mg, 1.91 mmol) resulted
in the title silyl ether 23 (260 mg, 55%). Spectral data for
this compound are identical to those obtained for the same
compound prepared by hydrolysis of the acetate 22a . The
intermediate syn diol 24a was never completely characterized.
2-(6-Am in o-9H-p u r in -9-yl)-6-O-[(1,1-d im eth yl)eth yld i-
m eth yl]silyl-1,5-an h ydr o-2,3,4-tr ideoxy-D-th r eo-h exitol (28)
a n d 2-(6-Am in o-7H -p u r in -7-yl)-6-O-[(1,1-d im et h yl)et h -
yld im eth yl]silyl-1,5-a n h yd r o-2,3,4-tr id eoxy-D-th r eo-h exi-
tol (29). Meth od A. A mixture of the mesylate 27 (28.5 mg,
0.088 mmol), adenine (23.8 mg, 0.18 mmol), potassium carbon-
ate (24.3 mg, 0.18 mmol), and 18-crown-6 (23.2 mg, 0.088
mmol) was taken up in N,N-dimethylformamide (2.5 mL) and
heated to 100 °C for 24 h. The solution was cooled, and the
solvent was evaporated on the rotary with heating. The
resulting solid was dissolved in methanol and adsorbed on
silica gel. Flash chromatography (10% MeOH in CHCl3) gave
the desired N-9 adduct 28 (11.7 mg, 37%) as well as the more
polar N-7 adduct 29 (2.3 mg, 7%) as pale yellow solids. Major
product 28. Mp: 122-124 °C. 1H NMR (500 MHz, CD3OD)
δ: 8.62 (1H, s), 8.23 (1H, s), 4.71 (1H, br s), 4.37 (1H, d, J )
12.8 Hz), 4.12 (1H, dd, J ) 12.8, 1.8 Hz), 3.79 (1H, dd, J )
10.9, 3.6 Hz), 3.73 (1H, dd, J ) 10.9, 4.2 Hz), 3.65-3.68 (1H,
m), 2.19-2.24 (2H, m), 1.55-1.70 (2H, m), 0.95 (9H, s), 0.14
(3H, s), 0.12 (3H, s). 13C NMR (100 MHz, CDCl3) δ: 157.31,
153.62, 150.53, 142.40, 79.32, 70.41, 67.20, 50.39, 28.41, 26.44,
22.88, 19.27, -5.18, -5.22 (one low-field carbon not resolved).
FT-IR (neat): 3296.8, 3138.6, 2926.4, 2855.0, 1676.3, 1605.0,
1304.0, 1126.6, 835.3 cm-1. MS (EI) m/z (rel intensity) 364.2
([M + H]+, 2), 306.1 (100). High-resolution EI MS (m/z):
249.1226. [R]25 ) -61.4 (c ) 0.3, CH3OH). Mp: 222-226
D
°C.
2-Am in o-6-(p h en ylm eth oxy)p u r in e (31). This purine
derivative was prepared from benzyl alcohol, sodium, and
2-amino-6-chloropurine 30 according to known literature
procedures.15
2-(2,6-Dia m in o-9H-p u r in -9-yl)-6-O-[(1,1-d im eth yl)eth -
yld im eth yl]silyl-1,5-a n h yd r o-2,3,4-tr id eoxy-D-th r eo-h exi-
tol (33). To a solution of the mesylate 27 (21.1 mg, 0.065
mmol) in N,N-dimethylformamide (1.5 mL) were added potas-
sium carbonate (18.0 mg, 0.13 mmol), 2,6-diaminopurine 32
(17.5 mg, 0.13 mmol), and 18-crown-6 (17.1 mg, 0.065 mmol).
The solution was heated to 110 °C for 16 h. The solvent was
evaporated under reduced pressure with heating, and the
residue was redissolved in methanol and adsorbed on silica
gel. Flash chromatography (7% MeOH in chloroform) gave the
desired N-9 adduct 33 as a film (8.4 mg, 34%). 1H NMR (400
MHz, CDCl3) δ: 8.21 (1H, s), 5.56 (2H, br s), 4.76 (2H, br s),
4.50 (1H, br s), 4.30 (1H, d, J ) 13.1 Hz), 3.97 (1H, dd, J )
12.7, 2.6 Hz), 3.72 (1H, dd, J ) 10.7, 5.2 Hz), 3.64 (1H, dd, J
) 10.7, 4.5 Hz), 3.54-3.60 (1H, m), 2.16-2.21 (1H, m), 1.98-
2.07 (1H, m), 1.49-1.59 (2H, m), 0.90 (9H, s), 0.09 (3H, s), 0.08
(3H, s). 13C NMR (100 MHz, CDCl3) δ: 159.58, 155.73, 138.60,
78.38, 69.68, 66.33, 48.09, 27.57, 25.97, 22.41, 18.45, -5.27
(two low-field carbons not resolved). FT-IR (neat): 3329.6,
3188.7, 2955.3, 2856.9, 1633.9, 1597.3, 1406.3, 1103.4, 839.1
cm-1. MS (EI) m/z (rel intensity) 378.2 ([M]+, 17), 321.1 (100),
150.1 (31). High-resolution EI MS (m/z): 378.2201, calcd for
364.2166, calcd for C17H30N5O2Si ([M + H]+) 364.2169. [R]25
D
) +9.6 (c ) 5, CH2Cl2). Minor product 29. 1H NMR (500 MHz,
CDCl3) δ: 9.02 (1H, s), 8.08 (1H, s), 5.03 (1H, s), 4.51 (1H, d,
J ) 13.6 Hz), 4.12 (1H, dd, J ) 13.6, 2.9 Hz), 3.70 (3H, m),
2.39 (1H, dm, J ) 14.7 Hz), 2.23 (1H, dt, J ) 14.1, 4.5 Hz),
1.64 (1H, dm, J ) 14.3 Hz), 1.52-1.58 (1H, m), 0.90 (9H, s),
0.09 (6H, s). 13C NMR (100 MHz, CDCl3) δ: 154.90, 150.35,
143.95 (2C's), 77.91, 68.00, 65.74, 53.30, 26.39, 24.99, 21.31,
17.82, -6.60, -6.66 (one low-field carbon not resolved). FT-
IR (neat): 2953.4, 2926.4, 2856.9, 1684.1, 1651.3, 1412.1,
1169.0 cm-1. MS (EI) m/z (rel intensity) 364.2 ([M + H]+, 7),
306.1 (100). High-resolution EI MS (m/z): 364.2170, calcd for
C
17H30N6O2Si 378.2199. [R]25 ) +38.3 (c ) 0.2, CH2Cl2).
D
2-(2-Acet yla m in o-6-a m in o-9H -p u r in -9-yl)-6-O-a cet yl-
1,5-a n h yd r o-2,3,4-tr id eoxy-D-th r eo-h exitol (35) a n d 2-(2,6-
Di(a cetyla m in o)-9H-p u r in -9-yl)-6-O-a cetyl-1,5-a n h yd r o-
2,3,4-t r id eoxy-D-th r eo-h exit ol (34). The diaminopurine
derivative 33 (125 mg, 0.33 mmol) was dissolved in acetic
anhydride (4 mL) and cooled to 0 °C. The solution was treated
with boron trifluoride etherate (0.15 mL, 1.25 mmol) and
stirred at 0 °C for 10 min and at room temperature for another
2 h. Saturated sodium bicarbonate solution (4 mL) was added
carefully to the reaction mixture. The mixture was extracted
with ethyl acetate (5 × 4 mL) and washed with brine. The
combined organic extracts were dried over MgSO4, and the
solvent was evaporated (with final coevaporation with toluene).
Flash column chromatography on silica gel (3% methanol in
chloroform) gave the diacetamide 34 (41 mg, 32%) as well as
the more polar monoacetamide 35 (28 mg, 24%). Diacetamide
34. 1H NMR (400 MHz, CDCl3) δ: 9.99 (1H, s), 9.41 (1H, s),
8.56 (1H, s), 4.66 (1H, s), 4.41 (1H, d, J ) 13.0 Hz), 4.18 (1H,
d, J ) 12.0, 3.4 Hz), 4.06 (1H, dd, J ) 11.8, 6.3 Hz), 4.03 (1H,
dd, J ) 12.9, 2.4 Hz), 3.77-3.81 (1H, m), 2.51 (3H, s), 2.44
(3H, s), 2.27 (1H, b dm, J ) 13.9 Hz), 2.07-2.14 (1H, m), 2.07
(3H, s), 1.41-1.57 (2H, m). 13C NMR (100 MHz, CDCl3) δ:
166.91 (2 C′s), 166.23, 148.56, 148.46, 145.95, 138.57, 114.46,
71.56, 65.24, 62.53, 44.77, 23.15, 21.28, 21.22, 18.21, 16.88.
MS (EI) m/z (rel intensity) 391.2 ([M + H]+, 51), 235.1 (38),
192.1 (96), 150.1 (100). High-resolution EI MS (m/z): 391.1729,
C
17H30N5O2Si ([M + H]+) 364.2169. [R]25 ) +20 (c ) 0.5,
D
MeOH).
Meth od B. A suspension of adenine (32.4 mg, 0.24 mmol),
sodium hydride (9.6 mg, 0.24 mmol), and 18-C-6 (12.7 mg, 0.05
mmol) in anhydrous DMF (1 mL) was heated at 85 °C for 0.5
h. A solution of mesylate 27 (40 mg, 0.12 mmol) in anhydrous
DMF (1 mL) was added to this suspension, and the resulting
mixture was heated at 100 °C overnight. The mixture was
then cooled and evaporated under reduced pressure with
heating. Water and ethyl acetate (3 mL each) were added to
the evaporation residue. The organic layer was separated, and
the aqueous layer was extracted with ethyl acetate (3 × 2 mL).
The combined organic extracts were dried over MgSO4, and
the solvent was evaporated. The residue was flash chromato-
graphed on silica gel (chloroform/methanol 9:1) to give the
adducts 28 and 29 in 27% and 10% yields, respectively. The
spectroscopic data for these two compounds are identical to
those of the compounds obtained under different conditions
above.
calcd for C17H23N6O5 ([M + H]+) 391.1730. [R]25 ) +82.1 (c
D
) 0.9, CH2Cl2). Monoacetamide 35. 1H NMR (400 MHz,
CDCl3) δ: 10.27 (1H, br s), 8.34 (1H, s), 4.58 (1H, br s), 4.43
(1H, d, J ) 13.2 Hz), 4.22 (1H, dd, J ) 11.8, 3.2 Hz), 4.08 (1H,
dd, J ) 11.8, 6.3 Hz), 4.05 (1H,dd, J ) 12.9, 2.5 Hz), 3.80 (1H,
2-(6-Am in o-9H-p u r in -9-yl)-1,5-a n h yd r o-2,3,4-tr id eoxy-
D-th r eo-h exit ol (7a ). To the solution of the silyl ether 28