Stereoisomeric Imidazolo-Pentoses
FULL PAPER
dropwise 1.5 DIBAH in toluene (20 mL, 30 mmol). After 20 min
vacuo and the residue was extracted with AcOEt, the organic phase
at Ϫ78 °C, MeOH (7 mL) was added dropwise and the reaction washed with brine, dried (MgSO4), filtered and concentrated to
allowed to warm to room temp. To this stirred solution a saturated
potassium sodium tartrate solution (7 mL) and AcOEt (40 mL)
were added. After 10 min, the solution was dried (MgSO4), the
suspension filtered and the filtrate dried once more (MgSO4), the
resulting suspension was filtered and the filtrate concentrated to
dryness. The residue was dissolved in toluene, centrifuged and the
filtrate concentrated to dryness, the residue taken up once more in
anhydrous toluene, and the solution concentrated to dryness, lead-
ing to the pure aldehyde 30 (ca. 3.5 g, quantitative; aldehyde hy-
drate being no longer detected by 1H NMR), which was used as
such for the following step. Ϫ 1H NMR (CDCl3): δ ϭ 9.72 [d, 1
dryness whereby an orange oil was obtained. This oily residue was
dissolved in THF (1.5 mL) and 2 HCl (65 mL) was added. The
resulting mixture was heated to 70 °C for 3 h, cooled to room temp.
and extracted with AcOEt, the aq. phase was adjusted with
NH4OH to pH ϭ 10, and extracted again with AcOEt. The com-
bined organic phases were washed with brine, dried (MgSO4), con-
centrated to dryness, and the oily residue was purified by FC (Et2O/
MeOH/NH4OHconc, 9:1:0.5) leading thereby to 32 (938 mg, 90%)
as colourless crystals (AcOEt/pentane), m.p. 132 °C. Ϫ [α]2D0 ϭ ϩ20
(c ϭ 1, MeOH). Ϫ 1H NMR (CDCl3): δ ϭ 7.63 [s, 1 H, HϪC(2Ј)],
7.37Ϫ7.21 (10 H, H-arom), 7.07 [s, 1 H, HϪC(5Ј)], 4.74 [d, 1 H,
H, HϪC(1)], 7.38Ϫ7.26 (m, 5 H, H-arom), 4.79 and 4.66 (2 H, AB, HϪC(1)], 4.62 and 4.51 (2 H, AB, J ϭ 11.3 Hz, CH2Ph), 4.57 and
J ϭ 11.9, CH2Ph), 4.38 [m, 1 H, HϪC(3)], 4.06 [dd, 1 H, HaϪC(4)], 4.42 (2 H, AB, J ϭ 11.7 Hz, CH2Ph), 3.96 [t, 1 H, HϪC(2)], 3.80
3.95 [dd, 1 H, HbϪC(4)], 3.86 [dd, 1 H, HϪC(2)], 1.43 (s, 3 H, CH3 [m, 1 H, HϪC(3)], 3.63Ϫ3.61 [m, 2 H, HaϪC(4) and HbϪC(4)],
acetonide), 1.35 (s, 3 H, CH3 acetonide), J1,2 ϭ 1.5, J3,4a ϭ 6.6, J1,2 ϭ 4.6, J2,3 ϭ 4.6 Hz. Ϫ Anal. calcd. for C21H24N2O4 (368.43):
J4a,4b ϭ 8.8, J3,4b ϭ 5.9, J2,1 ϭ 1.5, J2,3 ϭ 5.4 Hz. Ϫ 13C NMR C 68.46, H 6.57, N 7.60; found C 68.3, H 6.3, N 7.4.
(CDCl3): δ ϭ 202.1 [C(1)], 136.9 (Cs arom), 128.6Ϫ128.1 (5C
L
-lyxo-Imidazolo-piperidinose Derivative 33: To a stirred solution of
arom), 109.8 (CMe2acetonide), 82.8 [C(2)], 75.3 [C(3)], 73.3
(CH2Ph), 65.3 [C(4)], 26.1 and 25.1 [C(CH3)2 acetonide).
32 (792 mg, 2.15 mmol) in CH2Cl2 (15 mL) and pyridine (770 µL,
9.5 mmol) at Ϫ30 °C was added Tf2O (760 µL, 4.63 mmol) drop-
wise. After 30 min, the reaction mixture was left to warm to room
temp., H2O was added and the solution extracted with CH2Cl2.
The organic solution was dried (MgSO4), filtered, concentrated to
dryness and the oily residue purified by FC (Et2O/MeOH/
NH4OHconc, 9:1:0.5), which led to 33 (244 mg, 32%) as a colourless
resin that crystallised, m.p. 129 °C. Ϫ [α]2D0 ϭ ϩ57 (c ϭ 1, MeOH).
The Coupling Reaction: To a stirred solution of 10 (4.81 g,
16.6 mmol) in anhydrous THF (70 mL) at Ϫ78 °C was added drop-
wise a 1.6 solution of nBuLi in hexane (11.4 mL, 18.3 mmol).
After 30 min, a solution of 30 (3.33 g, 13.3 mmol) in anhydrous
THF (10 mL) was added and the mixture was left to warm to room
temp. After ca. 1 h, a sat. aq. solution of Na2CO3 was added, the
mixture extracted with AcOEt and the organic solution washed
with H2O, dried (MgSO4) and concentrated to dryness. The re-
sulting brownish oil (two diastereoisomers) was separated by FC
(AcOEt/cyclohexane, 2:8 then 5:5), the major product 31 (3.29 g,
46%) being the less polar one as a yellow oil, and its more polar
diastereoisomer (2.44 g, 34%) as an orange oil.
1
Ϫ H NMR (CDCl3): δ ϭ 7.50 [s, 1 H, HϪC(3)], 7.38 (10 H, H-
arom), 7.08 [s, 1 H, HϪC(1)], 4.77 [d, 1 H, HϪC(8)], 4.70 and 4.47
(2 H, AB, J ϭ 11.8 Hz, CH2Ph), 4.64 and 4.40 (2 H, AB, J ϭ
12.2 Hz, CH2Ph), 4.69 [td, 1 H, HϪC(6)], 4.52 [dd, 1 H, HaϪC(5)],
3.74 [dd, 1 H, HbϪC(5)], 3.60 [dd, 1 H, HϪC(7)], J5a,6 ϭ 6.6,
J5a,5b ϭ 12.2, J5b,6 ϭ 9.5, J6,7 ϭ 9.5, J7,8 ϭ 3.3 Hz. Ϫ 13C NMR
(CDCl3): δ ϭ 140.1 [C(3)], 136.9 (2 Cs), 129.3 [C(1)], 128 to 128.6
(C-arom), 127.8 [C(8a)], 79.9 [C(7)], 71.5 (CH2Ph), 69.7 (CH2Ph),
65.1 [C(8)], 64.5 [C(6)], 47.5 [C(5)].
Major L
-lyxo-Diastereoisomer (1S)-31: 1H NMR (CDCl3): δ ϭ 7.47
[s, 1 H, HϪC(5Ј)], 7.37Ϫ7.24 (m, 5 H, H-arom), 5.09 [dd, 1 H,
HϪC(1)], 4.84 and 4.61 (2 H, AB, J ϭ 11.4, CH2Ph), 4.23 [ddd, 1
H, HϪC(3)], 3.89 [dd, 1 H, HaϪC(4)], 3.82 [t, 1 H, HϪC(2)], 3.75
[dd, 1 H, HbϪC(4)], 3.23 (d, 1 H, OH), 2.77 [s, 6 H, N(CH3)2], 1.45
and 1.35 (2 ϫ 3 H, CH3 isoprop), 1.00 [s, 9 H, SiC(CH3)3], 0.39 [s,
6 H, Si(CH3)2], J1,OH ϭ 7.0, J1,2 ϭ 5.4, J2,3 ϭ 5.5, J3,4a ϭ 6.5,
J3,4b ϭ 7.4, J4a,4b ϭ 8.5 Hz. Ϫ 13C NMR (CDCl3): δ ϭ 156.1,
138.1, 134.2, 131.9, 128.4Ϫ127.8, 109.5, 81.6, 76.9, 74.0, 66.0, 64.9,
37.5, 27.3, 26.4, 25.6, 18.4, Ϫ3.4 and Ϫ3.6.
L-lyxo-Imidazolo-piperidinose (ent-4): A stirred solution of 33
(175 mg, 0.50 mmol) in MeOH (3 mL) was put under H2 (20 bar)
for 4 d in the presence of 10% Pd/C (200 mg) at room temp. The
suspension was filtered through Clarcel, the solution concentrated
to dryness and the residue purified by FC (Et2O/MeOH/
NH4OHconc, 6:4:0.5) leading to ent-4 (54 mg, 63%) as a colourless
powder, m.p.dec. 205 °C (MeOH/iPrOH). Ϫ [α]2D0 ϭ ϩ11 (c ϭ 0.5,
MeOH). Ϫ CD: 215.0 (Ϫ3.45), 199.5 (ϩ4.75), 188.5 (ϩ2.10). Ϫ
The 1H NMR and 13C NMR spectra are identical and superimpos-
able with those of 4 and with those reported previously.[10]
Minor
L
-xylo-Diastereoisomer (1R)-31: 1H NMR (CDCl3): δ ϭ
7.33Ϫ7.30 [m, 6 H, H-arom and HϪC(4Ј)], 5.00 [ddd, 1 H,
HϪC(1)], 4.73 and 4.43 (2 H, AB, J ϭ 10.8 Hz, OCH2Ph), 4.38
[dt, 1 H, HϪC(3)], 3.97 [dd, 1 H, HaϪC(4)], 3.81 [dd, 1 H,
HbϪC(4)], 3.75 [dd, 1 H, HϪC(2)], 3.17 (d, 1 H, ϪOH), 2.82 [s, 6
H, N(CH3)2], 1.44 and 1.38 [2 s, 6 H, C(CH3)2], 0.99 [s, 9 H,
SiC(CH3)3], 0.41 and 0.40 [2 s, 6 H, SitBu(CH3)2], J1,5Ј ϭ 0.6,
D
-ribo-Imidazole Derivative 35: A pressure vessel, which had been
prepared according to ref.[21,22], containing 3-O-benzyl--allose
(34) (6.15 g, 22.8 mmol), formamidine acetate (3.32 g, 31.9 mmol),
and liquid ammonia (ca. 40 mL), was heated to 80 °C for 15 h
under stirring whereby the pressure rose to 40 atm. The workup
was performed as for 22 and gave 35 (3.34 g, 53%) as a yellow oil
which was purified by FC (AcOEt/MeOH/NH4OHconc, 8:1:0.1 then
J1,OH ϭ 7.2, J1,2 ϭ 2.8, J2,3 ϭ 6.2, J3,4a ϭ 6.3, J3,4b ϭ 7.4, J4a,4b
ϭ
8.3 Hz. 156.1, 137.5, 134.7,
Ϫ
13C NMR (CDCl3):
δ ϭ
128.5Ϫ128.0, 109.5, 80.9, 77.5, 74.9, 65.8, 65.7, 37.6, 27.3, 26.5,
25.7, 18.3, Ϫ3.4, Ϫ3.6.
4:1:0.1). Ϫ [α]2D0 ϭ ϩ52 (c ϭ 1.0, MeOH). Ϫ H NMR (CD3OD):
1
δ ϭ 7.68 [d, 1 H, HϪC(2Ј)], 7.30Ϫ7.20 (m, 5 H, H-arom), 7.08 [d,
1 H, HϪC(5Ј)], 4.69 [d, 1 H, HϪC(1)], 4.46 and 4.35 (2 H, AB,
J ϭ 11.6 Hz, CH2Ph), 3.99 [dd, 1 H, HϪC(2)], 3.71 [dd, 1 H,
HaϪC(4)], 3.59 [dd, 1 H, HbϪC(4)], 3.41 [ddd,1 H, HϪC(3)],
L-Imidazolo-lyxose Derivative 32: To a stirred solution of (1S)-31
(1.735 g, 3.21 mmol) in anhydrous THF (60 mL) was added a cata-
lytic amount of Bu4NI (200 mg) and 50% NaH in oil (450 mg,
18.8 mmol) at room temp. The reaction mixture was heated to 40
°C and BnBr (0.8 mL, 6.77 mmol) was added. After 2 h, the reac-
J2Ј,5Ј ϭ 1.2, J1,2 ϭ 4.7, J2,3 ϭ 7.4, J3,4a ϭ 3.4, J3,4b ϭ 6.1, J4a,4b
ϭ
11.4 Hz. Ϫ 13C NMR (CD3OD): δ ϭ 139.5, 129.3, 129.0, 128.6 (C-
tion mixture was cooled to room temp. and MeOH (5 mL) and arom), 136.8 [C(2Ј)], 134.2 [C(4Ј)], 122.6 [C(5Ј)], 76.3 [C(1)], 75.0
H2O (5 mL) were added. The organic solvents were evaporated in
[C(2)], 73.4 [C(3)], 71.4 (CH2Ph), 64.5 [C(4)].
Eur. J. Org. Chem. 2001, 1335Ϫ1347
1345