S. Jessel, C. Meier
FULL PAPER
foam. [α]2D0 = –8.0 (c = 0.39, CHCl3). Rf (TLC) = 0.31 (CH2Cl2/
CH3OH 9:1). 1H NMR (400 MHz, CDCl3): δ = 8.94 (brs, 1 H,
NH), 7.28 (d, 4J = 1.0 Hz, 1 H, 6-H), 5.00–4.96 (m, 1 H, 1Ј-H),
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2
3
4
3.65 (dd, J = 10.4, J = 5.9 Hz, 1 H, 5Јa-H), 3.59 (dd, J = 10.4,
4
3J = 7.5 Hz, 1 H, 5Јb-H), 2.63–2.53 (m, 1 H, 4Ј-H), 1.93 (d, J =
1.0 Hz, 3 H, CH3), 1.85–1.78 (m, 1 H, 3Ј-H), 1.71–1.64 (m, 1 H,
6Јa-H), 1.44–1.35 (m, 2 H, 2Ј-H, 6Јb-H), 0.69–0.62 (m, 1 H, 7Јa-
H), 0.44–0.38 (m, 1 H, 7Јb-H) ppm. 13C NMR (101 MHz, CDCl3):
δ = 163.7 (C-4), 150.9 (C-2), 137.0 (C-6), 110.5 (C-5), 65.1 (C-5Ј),
57.3 (C-1Ј), 40.5 (C-4Ј), 32.2 (C-6Ј), 20.5 (C-3Ј), 20.4 (C-2Ј), 12.7
(CH3), 4.8 (C-7Ј) ppm. UV: λmax = 271 nm (CH3CN). HRMS-
FAB: m/z calcd. for C12H16N2O3 [M + H]: 237.2744; found
237.2753.
(1R,2R,4R,5R)-4-(Benzyloxymethyl)bicyclo[3.1.0]hexan-2-ol (31):
DIAD (320 μL, 1.63 mmol) was slowly added at 0 °C under nitro-
gen to a suspension of PPh3 (427 mg, 1.63 mmol) in anhyd. Et2O
(6 mL) and the suspension was stirred for 0.5 h. This preformed
complex was slowly added at 0 °C to a suspension of benzoic acid
(200 mg, 1.63) and the alcohol 29 (178 mg, 816 μmol) in anhyd.
Et2O (10 mL). The reaction mixture was allowed to warm slowly
to room temp. and stirred overnight. The solvent was removed and
methanolic NaOH solution (1%, 10 mL) was added. The reaction
mixture was stirred for an additional 6 h at room temp. The solu-
tion was neutralized by addition of HCl (1 m) and then concen-
trated. The residue was purified on silica gel (hexane/EtOAc 1:1)
[3]
to yield 31 (127 mg, 583 μmol, 71%) as a colorless syrup. [α]2D0
=
1
–21.0 (c = 0.81, CHCl3). Rf (TLC) = 0.50 (hexane/EtOAc 1:1). H
NMR (400 MHz, CDCl3): δ = 7.37–7.26 (m, 5 H, Bn arom.), 4.54
2
3
(s, 2 H, PhCH2), 4.24–4.21 (m, 1 H, 2-H), 3.44 (dd, J = 9.1, J =
7.8 Hz, 1 H, 7a-H), 3.40 (dd, 2J = 9.1, 3J = 6.4 Hz, 1 H, 7b-H),
2.82–2.73 (m, 1 H, 4-H), 1.68–1.61 (m, 1 H, 3a-H), 1.57–1.52 (m,
1 H, 5-H), 1.44–1.39 (m, 1 H, 1-H), 1.03 (ddd, 2J = 15.1, 3J = 11.0,
5.0 Hz, 1 H, 3b-H), 0.43–0.37 (m, 1 H, 6a-H), 0.15–0.09 (m, 1 H,
6b-H) ppm. 13C NMR (101 MHz, CDCl3): δ = 138.7 (C arom.q),
128.3, 127.4, 127.4 (C arom.), 74.3 (C-2), 73.1 (C-7), 73.0 (CH2-
Bn), 37.5 (C-4), 34.3 (C-3), 24.3 (C-1), 18.7 (C-5), 4.5 (C-6) ppm.
IR (film): ν = 3355, 3065, 3032, 3002, 2903, 1716, 1495, 1452, 1388,
˜
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375–377; b) J. H. Cho, D. L. Bernard, R. W. Sidwell, E. R.
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1351, 1315, 1272, 1177, 1109, 1095, 1070, 1025, 989, 960, 937, 835,
816, 734, 712, 698, 650, 600, 530, 440 cm–1. MS-FAB: m/z calcd.
for C14H18O2 [M + H]: 219.3; found 219.1.
L-carba-2Ј,3Ј-endo-Methylene-β-thymidine (32): The reaction was
carried out by the General Coupling Procedure with PPh3 (230 mg,
870 μmol) in CH3CN (4 mL), DIAD (160 μL, 815 μL), N3-benzo-
ylthymine (134 mg, 582 μmol), the cyclopentanol 31 (63.6 mg,
291 μmol) in CH3CN (6 mL), and NaOH in MeOH (1%, 6 mL).
The residue was directly debenzylated by the General Debenz-
ylation Procedure. The crude product was purified by chromatog-
raphy with a chromatotron (CH2Cl2/MeOH gradient 0–5%). After
lyophilization (CH3CN/water) the debenzylated nucleoside 32
(19.8 mg, 84.5 μmol, 29%) was obtained as a colorless foam. [α]2D0
= –7.5 (c = 0.31, H2O). Rf (TLC) = 0.28 (CH2Cl2/CH3OH 9:1). 1H
4
NMR (400 MHz, D2O): δ = 7.92 (d, J = 1.0 Hz, 1 H, 6-H), 4.90
[6]
[7]
3
2
3
(ddd, J = 10.5, 7.2, 3.7 Hz, 1 H, 1Ј-H), 3.60 (dd, J = 10.8, J =
6.3 Hz, 1 H, 5Јa-H), 3.54 (dd, 2J = 10.8 Hz, J = 7.8 Hz, 1 H, 5Јb-
3
H), 2.59–2.48 (m, 1 H, 4-HЈ), 2.13 (ddd, 2J = 14.6 Hz, 3J = 6.6,
6.6 Hz, 1 H, 6Јa-H), 1.91 (d, 4J = 1.0 Hz, 3 H, CH3), 1.64–1.55 (m,
1 H, 3Ј-H), 0.88–0.77 (m, 2 H, 6Јb-H, 7Јa-H), 0.73–0.67 (m, 1 H,
7Јb-H) ppm. 13C NMR (101 MHz, D2O): δ = 166.5 (C-4), 152.7
(C-2), 139.5 (C-6), 109.6 (C-5), 63.4 (C-5Ј), 58.2 (C-1Ј), 38.8 (C-
4Ј), 26.5 (C-6Ј), 16.8 (C-3Ј), 16.4 (C-2Ј), 11.1 (CH3), 2.0 (C-7Ј) ppm.
HRMS-FAB: m/z calcd. for C12H16N2O3 [M + H]: 237.2744; found
237.2746. UV: λmax = 271 nm (CH3CN).
[8]
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