E.-L. Tsou et al. / Tetrahedron 65 (2009) 93–100
97
20
give 1f (53%) as a colorless oil. [
(600 MHz, CDCl3)
a]
ꢁ113.8 (c 0.8, CHCl3); 1H NMR
the residue was extracted with CH2Cl2 and water. The organic layers
were dried with MgSO4, concentrated, and purified by CC (20%
EtOAc in hexanes, silica gel) to give 17 (1.27 g, 2.4 mmol, 74% from
2b) as a syrup. 1H NMR (600 MHz, CDCl3, mixture of conformers,
D
d
3.59 (dd, 1H, J¼2.5, 10.4 Hz), 4.09 (m, 1H), 4.12
(dd, 1H, J¼2.5, 10.4 Hz), 4.38 (d, 1H, J¼11.9 Hz), 4.43 (dd, 1H, J¼4.7,
5.9 Hz), 4.52 (dd, 2H, J¼7.4, 11.9 Hz), 4.57–4.68 (m, 4H), 6.95 (s, 1H),
7.18 (t, 2H, J¼1.4 Hz), 7.26–7.33 (m, 13H); 13C NMR (150 MHz, CDCl3)
major/minor¼2:1) (for a major conformer):
d 1.42 (s, 9H), 3.47–3.53
(m, 1H), 3.75 (dd, 1H, J¼4.1, 8.8 Hz), 3.84–3.90 (m, 3H), 4.05–4.08
d
137.5, 137.3, 137.1, 133.9, 128.7, 128.5, 128.4, 128.2, 128.1, 128.09,
128.05, 127.8, 127.6, 76.4, 75.4, 74.5, 73.4, 72.4, 72.1, 64.7. HRMS
(m, 2H), 4.15 (s, 1H), 4.38–4.67 (m, 6H), 7.18–7.35 (m, 15H); (for
calcd for [C26H27NO4þH]þ 418.2013, found 418.2042.
a minor conformer): d 1.47 (s, 9H), 3.47–3.53 (m, 1H), 3.72–3.76 (m,
1H), 3.80 (dd, 2H, J¼4.0, 11.4 Hz), 3.97 (s, 1H), 4.01 (dd, 1H, J¼4.1,
8.5 Hz), 4.17 (s, 1H), 4.28 (dd, 1H, J¼3.5, 10.3 Hz), 4.38–4.67 (m, 6H),
7.18–7.35 (m, 15H); 13C NMR (150 MHz, CDCl3, mixture of con-
4.2.7. (2R,3S,4S)-3,4-Bis(benzyloxy)-2-(benzyloxymethyl)-3,4-
dihydro-2H-pyrrole-1-oxide (1g)
The reaction was carried out as described above for 1a starting
formers) d 155.6, 154.2, 138.7, 138.3, 137.6, 137.5, 137.2, 128.7, 128.6,
from 2,3,5-tri-O-benzyl-
to give 1g (54%) as a colorless oil. [
(600 MHz, CDCl3)
b
-
D
-xylofuranose, derived from
D
-xylose,
128.5, 128.2, 128.1, 128.06, 128.01, 127.9, 127.8, 127.7, 127.6, 85.8,
84.3, 81.9, 80.9, 80.5, 80.4, 73.2, 73.2, 71.5, 71.4, 71.39, 71.32, 68.5,
68.0, 66.6, 65.6, 64.6, 63.6, 63.2, 62.4, 28.6, 28.5. HRMS calcd for
[C32H39NO6þNa]þ 556.2670, found 556.2661.
20
a]
þ72.7 (c 1, CHCl3); 1H NMR
D
d
3.82 (dd, 1H, J¼2.0, 10.1 Hz), 4.00 (dd, 1H,
J¼4.4, 10.1 Hz), 4.15 (br, 1H), 4.36 (dd, 1H, J¼4.4, 7.6 Hz), 4.49–4.76
(m, 6H), 4.77 (dd, 1H, J¼1.6, 2.5 Hz), 6.84 (s, 1H), 7.28–7.34 (m,
15H); 13C NMR (150 MHz, CDCl3)
d
137.6, 137.0, 136.9, 133.1, 128.2,
4.3.3. (2R,3R,4R,5R)-2,5-Bis(hydroxymethyl)pyrrolidine-3,4-diol
(4, DMDP)
128.1, 128.0, 127.8, 127.7, 127.6, 127.5, 127.2, 82.8, 80.2, 73.8, 73.2,
72.7, 72.0, 64.1. HRMS calcd for [C26H27NO4þH]þ 418.2013, found
418.2017.
A mixture of 17 (0.3 g, 0.56 mmol) and palladium hydroxide
(0.03 g) in MeOH was stirred for overnight under a hydrogen
atmosphere. The reaction mixture was filtered through Celite
and the filtrate was concentrated. The residue was treated with
the solution of CH2Cl2/TFA (2 mL/2 mL) and the reaction mix-
ture was stirred at 0 ꢀC for 30 min. The reaction mixture was
concentrated and purified by CC (25% aqueous NH4OH in
4.2.8. (2S,3S,4S)-3,4-Bis(benzyloxy)-2-(benzyloxymethyl)-3,4-
dihydro-2H-pyrrole-1-oxide (1h)
The reaction was carried out as described above for 1b starting
from 2,3,5-tri-O-benzyl-
give 1h (74%) as a white solid. [
(600 MHz, CDCl3)
b-D-xylofuranose, derived from D-xylose, to
þ37.3 (c 1, CHCl3); 1H NMR
propanol, silica gel) to give 4 (71.47 mg, 0.44 mmol, 78%) as
20
a]
D
20
d
3.77 (d, 1H, J¼3.9, 10.2 Hz), 4.01 (br, 1H), 4.05
a syrup (free form). [
D2O)
a
]
þ53.4 (c 0.6, H2O); 1H NMR (600 MHz,
D
(dd, 1H, J¼5.0, 10.2 Hz), 4.38 (t, 1H, J¼2.4, 3.2 Hz), 4.50–4.55 (m,
d
3.34 (dd, 2H, J¼3.4, 5.8 Hz), 3.73 (dd, 2H, J¼6.1, 12.3 Hz),
5H), 4.60 (d, 1H, J¼12 Hz), 4.65 (br, 1H), 6.89 (s, 1H), 7.24–7.33 (m,
3.81 (dd, 2H, J¼3.8, 12.3 Hz), 3.95 (dd, 2H, J¼2.2, 5.8 Hz); 13C
15H); 13C NMR (150 MHz, CDCl3)
d
137.6, 137.1, 137.0, 132.8, 128.5,
NMR (150 MHz, D2O) d 75.5, 62.1, 59.2. HRMS calcd for
128.4, 128.3, 128.0, 127.9, 127.8, 127.7, 127.6, 127.5, 82.6, 80.2, 77.4,
73.4, 71.8, 71.5, 66.0. HRMS calcd for [C26H27NO4þNa]þ 440.1832,
found 440.1818.
[C6H13NO4þH]þ 164.0917, found 164.0899.
4.3.4. (2S,3S,4S,5S)-2,5-Bis(hydroxymethyl)pyrrolidine-3,4-diol
(5,
L
-DMDP)
4.3. Typical procedure for the preparation of DMDP from 1a
(1a/2b/17/4)
The reaction was carried out as described above for 4 starting
20
from 1h to give 5 (free form, 50% yield from 1h) as a syrup. [a]
D
ꢁ51.0 (c 0.2, H2O); 1H NMR (600 MHz, D2O)
d 3.17 (br, 2H), 3.71 (dd,
4.3.1. (2R,3R,4R)-3,4-Bis(benzyloxy)-2(benzyloxymethyl)-5-
vinylpyrrolidin-1-ol (2b)
2H, J¼6.0, 11.6 Hz), 3.79 (d, 2H, J¼11.7 Hz), 3.92 (t, 2H, J¼2.2 Hz); 13C
NMR (150 MHz, D2O)
d 77.1, 61.7, 61.2. HRMS calcd for
Compound 1a (2 g, 5 mmol) was dissolved in THF (20 mL) and
then vinyl magnesium chloride (0.54 g, 6 mmol) was added drop-
wise at 0 ꢀC under Ar(g). After 15 h, the reaction mixture was
quenched with aqueous NH4Cl solution, extracted with CH2Cl2,
dried with MgSO4, and concentrated. The crude sample was puri-
[C6H13NO4þH]þ 164.0917, found 164.0933.
4.3.5. (2S,3R,4S,5S)-2,5-Bis(hydroxymethyl)pyrrolidine-3,4-diol
(6,
L
-DALDP)
The reaction was carried out as described above for 4 starting
20
fied by CC (25% EtOAc in hexanes, silica gel) to give 2b (1.91 g,
from 1d to give 6 (free form, 46% yield from 1d) as a syrup. [a]
D
20
4.3 mmol, 90%) as a brown solid. [
NMR (600 MHz, CDCl3)
a
]
ꢁ19.6 (c 0.66, CHCl3); 1H
ꢁ29.1 (c 1, H2O); 1H NMR (600 MHz, D2O)
d 3.20 (m, 1H), 3.37 (m,
D
d
3.56 (t, 1H, J¼4.9 Hz), 3.68 (dd, 1H, J¼6.0,
1H), 3.67 (m, 2H), 3.78 (dd, 1H, J¼3.9, 11.8 Hz), 3.82 (dd, 1H, J¼6.6,
9.8 Hz), 3.73 (dd,1H, J¼4.9, 9.8 Hz), 3.84 (t,1H, J¼8.1 Hz), 3.91 (t,1H,
11.3 Hz), 4.03 (dd, 1H, J¼4.3, 8.6 Hz), 4.21 (t, 1H, J¼4.0 Hz); 13C NMR
J¼5.0 Hz), 3.99 (t, 1H, J¼3.8 Hz), 4.45–4.56 (m, 6H), 5.31 (q, 2H),
(150 MHz, D2O)
d 73.2, 71.7, 61.5, 61.4, 60.1, 59.9. HRMS calcd for
6.02 (m, 1H), 7.23–7.31 (m, 15H); 13C NMR (150 MHz, CDCl3)
d
138.0,
[C6H13NO4þH]þ 164.0917, found 164.0892.
137.9, 137.8, 135.5, 128.1, 128.0, 127.9, 127.7, 127.6, 127.5, 127.4,
127.39, 127.35, 119.0, 85.9, 83.6, 73.0, 72.5, 71.6, 71.4, 69.5, 67.5.
HRMS calcd for [C28H31NO4þH]þ 446.2326, found 446.2344.
4.3.6. (2S,3S,4R,5R)-2,5-Bis(hydroxymethyl)pyrrolidine-3,4-diol
(7, DADP)
The reaction was carried out as described above for 4 starting
20
4.3.2. (2R,3R,4R,5R)-tert-Butyl-3,4-bis(benzyloxy)-2-(benzyloxy-
methyl)-5-(hydroxymethyl)-pyrrolidine-1-carboxylate (17)
from 1f to give 7 (free form, 43% yield from 1f) as a syrup. [a]
D
þ39.2 (c 2, H2O); 1H NMR (600 MHz, D2O)
d 3.06–3.09 (m, 2H), 3.65
A mixture of 2b (1.44 g, 3.2 mmol) and zinc powder (0.21 g,
3.2 mmol) in acetic acid was stirred at rt for 8 h. The reaction
mixture was filtered through Celite and the filtrate was neutralized
by aqueous NaHCO3 solution and extracted with CH2Cl2. The or-
ganic layers were dried with MgSO4, concentrated, and directly
reacted with di-tert-butyldicarbonate (0.88 g, 4 mmol) in CH2Cl2
(10 mL) in the presence of triethylamine (1 mL) to give a crude Boc-
protected amine compound. After ozonolysis and reduction with
NaBH4 (0.24 g, 6.3 mmol), the reaction solvent was removed and
(dd, 2H, J¼6.2, 11.7 Hz), 3.73 (dd, 2H, J¼4.2, 11.7 Hz), 3.84–3.87 (m,
2H); 13C NMR (150 MHz, D2O)
d 77.5, 61.6, 61.5. HRMS calcd for
[C6H13NO4þH]þ 164.0917, found 164.0858.
4.3.7. (2S,3R,4R,5R)-2,5-Bis(hydroxymethyl)pyrrolidine-3,4-diol
(13, DGDP)
The reaction was carried out as described above for 4 starting
20
from 1b to give 13 (43% from 1b) as a syrup. [
a
]
þ18.1 (c 1,
D
H2O); 1H NMR (600 MHz, D2O)
d
3.05 (d, 1H, J¼5.40 Hz), 3.35 (d,