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H.R. Moon et al. / Tetrahedron 66 (2010) 6707e6717
temperature was gradually allowed to reach ambient conditions.
The solution was then partitioned between ethyl ether (250 mL)
and water (100 mL), and the organic layer was washed with brine
(30 mL), dried (MgSO4), filtered, and reduced to dryness. The resi-
due was purified by silica gel column chromatography (hexanes/
EtOAc, 20:1) to give aldehyde 6 (9.0 g, 99%) as a clear oil; dH
(250 MHz, CDCl3) 9.54 (d, J¼4.9 Hz,1H, CHO), 4.04 (d, J¼10.9 Hz,1H,
OCHHSiA), 3.89 (d, J¼10.1 Hz, 1H, OCHHSiB), 3.65 (d, J¼10.9 Hz, 1H,
OCHHSiA), 3.53 (d, J¼10.2 Hz, 1H, OCHHSiB), 1.99 (dt, J¼7.8, 5.1 Hz,
1H, cyclopropane-CH), 1.50 (t, J¼5.0 Hz, cyclopropane-CHH), 1.28
(dd, J¼7.8, 4.6 Hz, 1H, cyclopropane-CHH), 0.96 (s, 9H, C(CH3)3),
0.94 (s, 9H, C(CH3)3), 0.12 (s, 6H, 2ꢃCH3), 0.11 (s, 3H, CH3), 0.09 (s,
3H, CH3); dC (100 MHz, CDCl3) 200.6, 64.5, 61.3, 37.7, 31.1, 26.0, 26.0,
18.4, 18.4, 16.3, ꢂ5.3, ꢂ5.3, ꢂ5.3, ꢂ5.4; FAB-MS m/z 301 (MHþ
eC4H10, 6%), 73 (100). Elemental analysis for C18H38O3Si: calcu-
lated: C, 60.28; H, 10.68. Found: C, 60.27; H, 10.71.
reduced to dryness and the residue was purified by silica gel flash
column chromatography (hexanes/EtOAc, 1:2) to give a mixture of
a
,
b
ꢂ(ꢀ)ꢂ9 (230 mg, 60%) as a sticky oil and a smaller amount
(67 mg, 18%) of second fraction that was deemed to be an epimeric
mixture of the minor N7-isomers.
4.7.7. [rel-(1S,4S,5S)-4-(6-Aminopurin-9-yl)-3-oxabicyclo[3.1.0]
hexyl]methan-1-ol [(ꢀ)-1]. A solution of
a
,
b
ꢂ(ꢀ)ꢂ9 (220 mg,
0.56 mmol) in saturated methanolic ammonia (6 mL) was stirred at
room temperature overnight. The volatiles were removed and the
residue was purified by silica gel flash column chromatography
(CH2Cl2/MeOH, 9:1) to give (ꢀ)-1 (83 mg, 60%) and the corre-
sponding :-anomer (21 mg, 15%).
a
-isomer [(ꢀ)-1]: white solid, mp 232e234 ꢁC; dH (250 MHz,
DMSO-d6) 8.51 (s, 1H, H-8), 8.19 (s, 1H, H-2), 7.34 (br s, 2H, NH2),
6.15 (s, 1H, H-40), 5.29 (t, J¼5.1 Hz, 1H, OH), 4.05 (d, J¼8.3 Hz, 1H,
H-20a), 3.98 (dd, J¼11.7, 5.0 Hz, 1H, CHHOH), 3.87 (d, J¼8.3 Hz, 1H,
H-20b), 3.64 (dd, J¼11.8, 5.1 Hz, 1H, CHHOH), 2.02 (dd, J¼8.3, 4.1 Hz,
1H, H-50), 1.00 (dd, J¼8.2, 4.7 Hz, 1H, H-60a), 0.70 (t, J¼4.4 Hz, 1H,
H-60b); dC (62.5 MHz, DMSO-d6) 155.9, 152.5, 149.0, 138.6, 118.7,
83.34, 69.03, 60.65, 31.27, 24.47, 12.59; FAB-MS m/z 248 (MHþ,
100%), 136 (bþ2Hþ, 36), 113 (26). Elemental analysis for
C11H13N5O2: calculated: C, 53.43; H, 5.30; N, 28.32. Found: C, 53.60;
H, 5.40; N, 28.05.
4.7.4. (rel-1S,2S,5S)-5-(Hydroxymethyl)-3-oxabicyclo[3.1.0]hexan-2-
ol [(ꢀ)-7]. A solution of aldehyde 6 (9.01 g, 25.1 mmol) in a mixture
of 1,4-dioxane (42 mL) and 1 N HCl (42 mL) was stirred at room
temperature for 16 h. The reaction mixture was neutralized with
DowexÒ anion exchange resin (OHꢂ) and filtered through a pad of
CeliteÒ. The filtrate was concentrated and the residue (3.26 g, 100%)
was used in the following step without further purification. An
analytical sample was obtained after silica gel flash column chro-
matography (CH2Cl2/MeOH, 22:1) to give pure (ꢀ)-7 as a clear oil;
dH (250 MHz, MeOH-d4) 5.09 (s, 1H, H-2), 3.96 (d, J¼8.1 Hz, 1H,
H-4a), 3.81 (d, J¼11.7 Hz, 1H, CHHOH), 3.74 (d, J¼8.1 Hz, 1H, H-4b),
3.60 (d, J¼11.7 Hz,1H, CHHOH),1.45 (dd, J¼8.1, 3.9 Hz,1H, H-1), 0.74
(ddd, J¼8.1, 4.7, 0.7 Hz, 1H, H-6a), 0.43 (t, J¼4.4 Hz, 1H, H-6b); dC
(100 MHz, CD3OD) 98.6, 68.8, 62.9, 29.8, 27.0, 11.8; FAB-MS m/z 113
(MHþꢂH2O, 100%) 83 (10). Elemental analysis for C6H10O3$0.3H2O:
calculated: C, 53.17; H, 7.88. Found: C, 52.97; H, 7.81.
a
-isomer white solid, mp 191e192 ꢁC; dH (250 MHz, DMSO-d6)
8.31 (s, 1H, H-8), 8.21 (s, 1H, H-2), 6.30 (d, J¼2.7 Hz, 1H, H-40), 4.11
(s, 2H, CH2OH), 3.76 (s, 2H, H-20a,b), 2.04e2.10 (m, 1H, H-50), 1.13
(t, J¼4.6 Hz, 1H, H-60a), 1.00 (dd, J¼7.7, 5.2 Hz, 1H, H-60b); dC
(62.5 MHz, MeOH-d4) 157.4, 154.0, 150.5, 140.0, 120.2, 86.3, 72.2,
63.5, 33.2, 25.8, 11.9; dC (100 MHz, CD3OD) 156.8, 152.7, 149.5,
138.8, 118.8, 85.0, 70.8, 62.2, 31.8, 24.4, 10.5; FAB-MS m/z 248
(MHþ, 100%), 136 (bþ2Hþ, 43), 113 (26). Elemental analysis for
C11H13N5O2$1.15H2O: calculated: C, 49.52; H, 5.35; N, 26.24.
Found: C, 49.78; H, 5.31; N, 26.05.
4.7.5. ((rel-1S,2R,5R)-5-(Acetyloxymethyl)-3-oxabicyclo[3.1.0]hexan-
2-yl) acetate [(ꢀ)-8]. A stirred solution of lactol (ꢀ)-7 (3.26 g,
25 mmol) in pyridine (25 mL) was treated with acetic anhydride
(11.85 mL, 125.6 mmol) at 0 ꢁC and allowed to reach room tem-
perature. After 5 h, the volatiles were removed under reduced
pressure and the residue was partitioned between EtOAc (200 mL)
and water (50 mL). The organic layer was dried (MgSO4), filtered,
and evaporated. The crude material was purified by silica gel flash
column chromatography (hexanes/EtOAc, 3:1) to give the diacetate
(ꢀ)-8 (3.64 g, 68%) as a clear oil; dH (250 MHz, CDCl3) 6.16 (s, 1H, H-
2), 4.48 (d, J¼12 Hz, 1H, CHHOAc), 4.23 (d, J¼12 Hz, 1H, CHHOAc),
4.10 (d, J¼8.1 Hz, 1H, H-4a), 3.99 (d, J¼8.3 Hz, 1H, H-4b), 2.17 (s, 3H,
C(O)CH3), 2.15 (s, 3H, C(O)CH3),1.77 (dd, J¼8.5, 4.2 Hz,1H, H-1), 0.97
(ddd, J¼8.6, 5.3, 0.7 Hz, 1H, H-6a), 0.76 (t, J¼4.9 Hz, 1H, H-6b); dC
(100 MHz, CDCl3) 171.1, 170.4, 98.9, 71.3, 65.2, 27.0, 26.6, 21.5, 21.0,
12.7; FAB-MS m/z 155 (MHþꢂAcOH, 100%). Elemental analysis for
C10H14O5: calculated: C, 56.07; H, 6.59. Found: C, 56.43; H, 6.68.
4.7.8. [(2R,3S)-3-(tert-Butyldimethylsilyloxy)-5-methoxytetrahy-
drofuran-2-yl]methanol (11). A stirred solution of compound 1011
(8.6 g, 34 mmol) in dry DMF (100 mL) was reacted with tert-
butyldimethylsilyl chloride (8.8 g, 58 mmol) and imidazole (7.0 g,
102 mmol) at room temperature for 20 h. After the addition of
EtOAc (200 mL), the organic phase was washed with water
(2ꢃ100 mL), dried (MgSO4), and reduced to dryness. The crude
product was taken up in CH2Cl2 (80 mL) and treated with a 25%
solution of NaOMe in methanol (10 mL). After stirring for 1 h at
room temperature, the entire mixture was loaded on a silica gel
column and then purified by flash chromatography (10/25%
EtOAc in hexanes) to give 11 (7.85 g, 87.7%) as an oily, 1:1 mixture of
isomers:
A and B; dH (400 MHz, CDCl3) 5.02 (dd, J¼5.6, 1.8 Hz, 0.5H, H-5A),
4.92 (dd, J¼5.9, 3.1 Hz, 0.5H, H-5B), 4.43 (m, 0.5H, H-3A), 4.13 (m, 0.5H,
H-3B), 3.95 (irregular q, J¼6.7, 4.0 Hz, 0.5H, H-2A), 3.81 (m, 1H,
CHHOHA, H-2B), 3.68 (dd, J¼11.9, 2.5 Hz, 0.5H, CHHOHA), 3.56 (dd,
J¼12.5, 4.4 Hz, 0.5H, CHHOHB), 3.53 (dd, J¼12.1, 3.6 Hz, 0.5H,
CHHOHB), 3.30 (s, 1.5H, OCH3/A), 3.29 (s, 1.5H, OCH3/B), 2.36 (ddd,
J¼13.8, 8.6, 6.5 Hz, 0.5H, H-40A), 2.13 (ddd, J¼13.5, 6.8, 1.7 Hz, 0.5H,
H-400A), 2.01 (dt, J¼13.5, 5.8 Hz, 0.5H, H-40B), 1.77 (ddd, J¼13.6, 6.1,
3.0 Hz, 0.5H, H-400B), 0.82 (s, 4.5H, C(CH3)3/A), 0.81 (s, 4.5H, C(CH3)3/B),
0.01 (s, 3H, SiCH3/A), 0.00 (s, 3H, SiCH3/B); dC (100 MHz, CDCl3, A/B
isomers) 110.4/109.3, 92.6/88.2, 76.7/75.7, 68.1/66.3, 60.2/60.0, 47.7/
46.9, 30.64/(overlapped), 22.85/22.83, 0.24/0.02; FAB-MS m/z 231
(MHþꢂCH3OH, 100%), 263 (MHþ, 2). Elemental analysis for
C12H26O4Si: calculated: C, 54.92; H, 9.99. Found: C, 54.70; H, 10.06.
4.7.6.
a
,
b
−[(rel-1R,5S)-3-Oxa-4-[6-(phenylcarbonylamino)purin-9-
-(ꢀ)-9]. A suspension of N-
yl]bicyclo[3.1.0]hexyl}methyl acetate [a,b
benzoyladenine (348 mg, 1.45 mmol) in acetonitrile (5 mL) was
treated with bis(trimethylsilyl)-trifluoroacetamide (BSTFA, 1 mL)
and stirred at room temperature for 1 h until a clear solution was
obtained. After removing the volatiles under reduced pressure and
under anhydrous conditions, a solution of diacetate (ꢀ)-8 (208 mg,
0.97 mmol) in acetonitrile (5 mL) was added and the resulting
mixture was cooled to ꢂ20 ꢁC before proceeding with the slow
addition of trimethylsilyl trifluoromethanesulfonate (TMSOTf,
0.26 mL, 1.42 mmol). The stirred mixture was gradually allowed to
reach room temperature and after 2 h, a saturated aqueous solution
of NaHCO3 was added. The mixture was filtered and the filtrate was
extracted with CH2Cl2 and dried (MgSO4). The organic solution was
4.7.9. (2S,3S)-Methyl 3-hydroxy-5-methoxytetrahydrofuran-2-car-
boxylate (12). A solution of 11 (2.93 g, 11.61 mmol) in acetonitrile/
water (1:1, 160 mL) was treated with bis(acetoxy)iodobenzene and