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4.4. 3-O-Benzyl-7-tert-butoxycarbonylamino-1,2-O-iso-
propylidene-5,6,7-trideoxy-a- -xylo-heptofuranose 10
(q, J=4.76 Hz, 2H, OCH2CH3), 4.42–4.65 (m, 3H),
4.70–4.78 (m, 1H), 5.95 (d, J=4.76 Hz, 1H, C1-H),
6.12 (d, J=14.3 Hz, 1H, olefinic), 6.90 (dd, J=4.8,
14.3 Hz, 1H, olefinic), 7.20–7.38 (m, 5H, aromatic);
EI MS: m/z 348 (M+); [h]D −27.2 (c 1, CHCl3).
D
To a cooled suspension of lithium aluminium hydride
(0.54 g, 0.014 mol) in dry THF (25 mL) at 0°C under
a nitrogen atmosphere, was added azide 9 (4 g, 0.012
mol). The reaction mixture was allowed to warm to
rt and stirred for 12 h, then cooled to 0°C and
quenched with 1N NaOH solution and extracted with
ethyl acetate. The combined organic extracts were
concentrated to give amine (2.0 g) as syrup.
4.2. 5,6-Dideoxy-3-O-benzyl-1,2-O-isopropylidene-a-
xylo-heptofuranose 8
D-
To a suspension of lithium aluminium hydride (1.08
g, 0.028 mol) in dry THF (100 mL) at 0°C under a
nitrogen atmosphere was added a solution of the con-
jugated ester 7 (5 g, 0.014 mol) in THF (25 mL) and
stirred at rt for 6 h. The reaction mixture was
quenched with a saturated solution of Na2SO4 at 0°C
and extracted with ethyl acetate. The combined
organic extracts were washed with water, brine, dried
(anhydrous, Na2SO4), concentrated and on purifica-
tion by column chromatography afforded saturated
alcohol 8 (3.74 g, 85%). IR (neat): 3400, 3030 cm−1;
1H NMR (200 MHz, CDCl3): l 1.30 (s, 3H, CH3),
1.48 (s, 3H, CH3) 1.54–1.94 (m, 4H, 2×CH2), 3.63 (t,
J=3.25 Hz, 2H, CH2OH), 3.75 (d, J=2.3 Hz, 1H,
C3-H), 4.10–4.20 (m, 1H, C4-H), 4.60 (d, J=2.8 Hz,
1H, C2-H), 4.40–4.70 (AB quartet, 2H, benzylic
CH2), 5.85 (d, J=2.8 Hz, 1H, C1-H), 7.20–7.40 (m,
5H, aromatic); EI MS: m/z 308 (M+); [h]D −15.2 (c 1,
CHCl3).
The above obtained crude amine (2 g, 0.006 mol) was
dissolved in dry CH2Cl2 (50 mL) cooled to 0°C, tri-
ethylamine (1.25 g, 0.012 mol) followed by Boc2O
(1.62 g, 0.078 mol) was added under a nitrogen atmo-
sphere and allowed to stir at rt for 3 h. The reaction
mixture was then extracted with DCM. The combined
organic extracts were washed with water, brine, dried
over anhydrous Na2SO4, concentrated and on purifi-
cation by column chromatography yielded protected
amine 10 (2.10 g, 43% overall) as a viscous liquid. IR
1
(neat): 1690 cm−1; H NMR (400 MHz, CDCl3): l 1.3
(s, 3H, CH3), 1.43 (s, 9H, 3×CH3), 1.46 (s, 3H, CH3),
1.52–1.70 (m, 3H), 1.72–1.85 (m, 1H), 3.14 (m, 2H,
CH2-NH-Boc), 3.72 (d, 1H, C3-H), 4.08 (m, 1H, C4-
H), 4.40–4.65 (AB quartet, 2H, benzylic CH2), 4.58
(d, 1H, C2-H), 5.85 (d, J=4 Hz, 1H, C1-H), 7.14–
7.19 (m, 5H, aromatic); 13C NMR (50 MHz, CDCl3):
l 25.3, 26.2, 26.7, 28.4, 40.5, 71.7, 79.0, 80.0, 82.1,
82.2, 104.6, 111.2, 127.7, 127.9, 128.4, 137.5, 155.9;
FAB MS: m/z 408 (M+1)+; [h]D−32.2 (c 1.25,
CHCl3).
4.3. 7-Azido-3-O-benzyl-1,2-O-isopropylidene-5,6,7-
trideoxy-a- -xylo-heptofuranose 9
D
To a stirred solution of alcohol 8 (2.5 g, 0.008 mol)
was added a solution of pyridine (1.3 g, 0.016 mol) in
dry CH2Cl2 (50 mL) at 0°C under a nitrogen atmo-
sphere. Tosyl chloride (2.3 g, 0.012 mol) was added
slowly and the reaction mixture was allowed to stir at
rt for 6 h. The reaction mixture was extracted with
CH2Cl2, washed with a CuSO4 solution, water, brine,
dried over anhydrous Na2SO4, concentrated and on
purification by column chromatography afforded
tosylate as a viscous liquid.
4.5. 7-tert-Butoxycarbonylamino-1,2-O-isopropylidene-
5,6,7-trideoxy-a- -xylo-heptofuranose 11
D
To liquid NH3 (100 mL) at −78°C, was added the
protected amine 10 (2 g, 0.0051 mol) in THF (10
mL), followed by metallic sodium (0.46 g, 0.0204
mol). After 2 h, ammonia was allowed to completely
evaporate by warming the reaction mixture to rt.
Then saturated NH4Cl was added and extracted with
CH2Cl2. The organic layers were washed with water,
brine, dried over anhydrous Na2SO4, concentrated
and purified by column chromatography to afford the
debenzylated alcohol 11 (1.25 g, 80%) as a syrupy
liquid. IR (neat): 3410, 1695 cm−1; 1H NMR (200
MHz, CDCl3): l 1.3 (s, 3H, CH3), 1.45 (s, 9H, 3×
CH3), 1.5 (s, 3H, CH3), 1.55–1.80 (m, 4H, 2×CH2),
3.10–3.23 (m, 2H, CH2-NH-Boc), 4.0–4.10 (m, 2H,
C3-H, C4-H), 4.48 (d, J=2.4 Hz, 1H, C2-H), 4.70
(bs, 1H, NH), 5.82 (d, J=2.4 Hz, 1H, C1-H); 13C
NMR (50 MHz, CDCl3): l 24.8, 26.1, 26.6, 26.7,
28.3, 40.5, 75.1, 79.3, 80.3, 85.3, 104.2, 111.2, 156.3;
EI MS: m/z 201 (M−116)+; [h]D −9.29 (c 1, CHCl3).
The above tosylate (2.5 g, 0.005 mol) was dissolved in
dry DMF (40 mL) and heated at 90°C with NaN3
(1.05 g, 0.015 mol) for 12 h. The reaction mixture
was brought to rt and diluted with water and
extracted with ether. The combined ethereal layers
were washed with water, brine, dried (anhydrous
Na2SO4), concentrated and on purification by column
chromatography yielded azide 9 (1.2 g, 68%). IR
(neat): 2097 cm−1; 1H NMR (400 MHz, CDCl3): l
1.30 (s, 3H, CH3), 1.45 (s, 3H, CH3), 1.50–1.58 (m,
1H), 1.60–1.75 (m, 2H), 1.76–1.85 (m, 1H), 3.20–3.36
(m, 2H, CH2N3), 3.75 (d, 1H, C3-H), 4.10 (m, 1H,
C4-H), 4.45–4.70 (AB quartet, 2H, benzylic CH2),
4.56 (d, 1H, C2-H), 5.86 (d, 1H, C1-H), 7.13–7.19 (m,
5H, aromatic); 13C NMR (50 MHz, CDCl3): l 25.3,
25.7, 26.1, 26.7, 51.4, 71.7, 79.7, 82.1, 82.2, 104.7,
111.3, 127.7, 127.9, 128.4, 137.5; EI MS: m/z 333
(M+); [h]D−49.1 (c 1, CHCl3).
4.6. 7-tert-Butoxycarbonylamino-1,2-O-isopropylidene-
5,6,7-trideoxy-a- -ribo-heptofuranose 13
D
To compound 11 (3 g, 0.01 mol) was added pyridinium
dichromate (7.11 g, 0.02 mol) in dry CH2Cl2 (70 mL) at