Synthesis of 1,4-dideoxy-1,4-iminoheptitol and 1,5-dideoxy-1,5-iminooctitols from d-xylose

Article abstract of DOI:10.1016/j.carres.2010.04.016

The synthesis of iminosugars from inexpensive d-xylose in high yields has been developed. The key step in this synthesis involves Wittig olefination or chelation-controlled attack of Grignard reagents on lactol and ring-closing metathesis using first or s

Full text of DOI:10.1016/j.carres.2010.04.016

Carbohydrate Research 345 (2010) 1142–1148
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis of 1,4-dideoxy-1,4-iminoheptitol and 1,5-dideoxy-1,5-iminooctitols
from D-xylose
*
Amit Kumar, Mohammed Abrar Alam, Shikha Rani, Yashwant D. Vankar
Department of Chemistry, Indian Institute of Technology, Kanpur 208 016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of iminosugars from inexpensive D-xylose in high yields has been developed. The key step
Received 11 March 2010
Received in revised form 5 April 2010
Accepted 18 April 2010
in this synthesis involves Wittig olefination or chelation-controlled attack of Grignard reagents on lactol
and ring-closing metathesis using first or second generation Grubbs’ catalysts.
Ó 2010 Elsevier Ltd. All rights reserved.
Available online 21 April 2010
Keywords:
Iminosugars
Lactol
Wittig olefination
Ring closing metathesis
Dihydroxylation
D-Xylose
1. Introduction
analogues produce considerable differences in inhibitory activity.
As part of an ongoing research project in our laboratory toward
Polyhydroxylated pyrrolidine and piperidine alkaloids, both nat-
ural and synthetic, have attracted considerable attention due to
their ability to inhibit glycosidases.1 Some inhibitors of glycosidases
have been identified as important chemotherapeutic agents with
application in the treatment of influenza,2 cancer,3 AIDS,4 and diabe-
tes.5 1,4-Dideoxy-1,4-iminoalditols,1b and 1,5-dideoxy-1,5-imino-
alditols1b are an important class of glycosidase inhibitors, which
are protonated at physiological pH and thus they mimic a glycopyr-
anosyl cation. Polyhydroxylated pyrrolidines and piperidines con-
nected to a polyhydroxy chain through C–C bonds (iminoalditols)
are considered as acyclic imino-C-disaccharide6 analogues, and they
act as glycosidase inhibitors. A large number of iminoalditols have
been found to be inhibitors of glycosidases. Thus, for example, 1,4-
the synthesis of natural and unnatural hybrid azasugars,15 we
became interested in developing new routes to iminoalditol
analogues with a view to assess their glycosidase inhibitory activ-
ity vis-à-vis the structural features. Our synthetic strategy relies on
the Wittig olefination or chelation-controlled nucleophilic addition
followed by the ring-closing metathesis (RCM) to form five- or six-
membered rings.
2. Results and discussion
A general retrosynthetic analysis is presented in Scheme 1. 1,4-
Dideoxy-1,4-iminoheptitol 16 and 1,5-dideoxy-1,5-iminooctitols
dideoxy-1,4-imino-
inhibitor of -mannosidases. Iminoheptitols such as 1,4-imino-
glycero- -ido (2) and 1,4-imino- -glycero-
-gluco-heptitols (3)8 are
good and specific inhibitors of - and b-glucosidases. Recently, Fleet
et al.9 reported that 1,4-imino-
-glycero- -talo-heptitol (4) is a
specific inhibitor of naringinase. Similarly, iminooctitols such as
1,4,7-trideoxy1,4-imino- -glycero-
-manno-octitol (5)10 and 1,5-
dideoxy-1,5-imino- -erthyro-
-talo-octitols (6)11 show moderate
glycosidase inhibition.
D
-mannitol7 1 (Fig. 1), an iminohexitol, is an
OH
a
L-
HO
OH
OH
HO
HO
OH
OH
D
L
D
OH
OH
a
N
OH
N
N
H
OH
D
L
H
H
OH
OH
3
1
2
D
L
OH
D
D
OH
HO
OH
HO
HO
OH
OH
OH
It has been observed that slight changes such as stereochemis-
OH
OH
OH
N
H
N
try,12 ring size,13 and hydroxyl group location14 in these sugar
OH
N
H
H
OH
OH
6
5
OH
4
* Corresponding author. Fax: +91 512 259 0007.
E-mail address: vankar@iitk.ac.in (Y.D. Vankar).
Figure 1. Structures of some selected iminoalditols.
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.04.016

A. Kumar et al. / Carbohydrate Research 345 (2010) 1142–1148
HO
1143
1. Tf2O, Py,
DCM, 0 0
OH
O
O
ref 16
C
BnO
OH
BnO
OMe
OMe
HO
D-Xylose
BnO
BnO
2. NaN3, DMF,
70 0C, 7 h, 91%
BnO
N
H
BnO
N3
OH
8
7
OH
N
Ac
OH
16
1. Ph3P, H 2O,
THF, 10 h
allyl bromide,
K2CO3, DMF
O
O
BnO
12
BnO
OMe
OMe
O
BnO
BnO
OH
2. Ac2O, Py, RT,
20 h, 85%
BnO
BnO
92%
N
NHAc
OH
10
9
Ac
N
HO
HO
OH
Ac
AcO OAc
N
11
O
Ph3CBF4, DCM,
RT, 1 h
BnO
BnO
BnO
OH
N
H
BnO
OH
93%
Ac
N
Ac
OH
18
11
24, 26
Scheme 2. Synthesis of common precursor lactol 11.
Scheme 1. Retrosynthetic analysis.
24 and 26 could be synthesized by the ring-closing metathesis
(RCM) of respective dienes. Compounds 12 and 18 could be ob-
11 in excellent yield. The diene 12 (Scheme 3) was prepared from
11 under standard Wittig conditions19 and the product underwent
ring-closing metathesis with the first generation Grubbs’ catalyst
tained from lactol 11, which is easily derived from
D
-xylose as
shown in Scheme 2.
A
20 (5 mol %) to give the expected cyclic compound 13 in 87% yield.
Thus, alcohol 7 (Scheme 2), obtained16 in two steps from
D-xy-
The olefin 13 was subjected to OsO4 mediated catalytic syn-dihydr-
oxylation and the corresponding diol was characterized as its triac-
etate 14 as a single diastereomer. Stereoselective dihydroxylation
was expected due to the stereodirecting effect of the C-5 substitu-
lose, on reaction with trifluoromethanesulfonic anhydride and pyr-
idine gave the corresponding 2-O-triflate derivative, which was not
isolated. The crude product, on reaction with NaN3 in DMF at 70 °C,
smoothly afforded the azido derivative 8 in 91% yield.
Reduction of the azido derivative 8 was achieved by treatment
with Ph3P in H2O and THF to afford the corresponding amine,
which was contaminated with phosphorus byproducts. The crude
amine was acetylated under standard conditions using acetic
anhydride and pyridine to give compound 9, whose N-allylation
with allyl bromide in the presence of K2CO3 led to monoallylated
compound 10 in 92% yield.
Deprotection of the anomeric acetal 10 under usual condi-
tions,17 however, was not clean and led to several products from
which the desired product could not be isolated. The problem
was, however, circumvented by developing18 an alternative meth-
od for the deprotection of anomeric acetals by the use of trip-
henylcarbenium tetrafluroborate, which gave the desired lactol
ent in 13.21 The cis dihydroxy groups were found to have
a-geom-
etry as revealed by 1H NMR spectroscopy and NOE spectral analysis
of the corresponding monoacetate 17, obtained later. Compound
17 showed NOE correlations between H-2 and H-5a; as well as
H-5b, H-4, and H-3 as shown in Figure 2. Hydrogenolysis of 14 with
10% palladium hydroxide on activated carbon followed by
acetylation gave pentaacetate 15 in 92% yield. This compound
was deacetylated22 with 4 N hydrochloric acid at 80 °C to give,
after purification over a column of Dowex 50 resin, 1,4-dideoxy-
1,4-imino-L-glycero-L-gluco-heptitol 16 (67%) as a syrup. Compound
15 upon deacetylation using NaOMe in MeOH gave the desired
N-acetylated derivate 17.
For the synthesis of 1,5-dideoxy-1,5-iminooctitols 24 and 26
(Scheme 4), lactol 11 was subjected to Grignard reaction with vinyl
Grubbs'
20
OH
BnO
catalyst'A'
Ph3PCH3Br,
BnO
n-BuLi, 0 ºC,
N
(5 mol%),
Ac
11
OH
BnO
4h, 92%
CH2Cl2, reflux
87%
N
OBn
Ac
12
13
AcO
OAc
AcO
OAc
1. OsO4, NMO, acetone /
H2O/ tBuOH (1:1: 0.5)
1. Pd/C, H2, 12 h
BnO
AcO
N
N
2. Ac2O, Py,
20 h, 92%
2.Ac2O, Et3N,CH2Cl2,
RT, 4 h, 89%
Ac
OAc
Ac
OAc
OBn
14
OAc
15
1. NaOMe, MeOH,
RT, 20 min
1. 4N HCl,
reflux, 7 h
2. dowex (OH- )
resin, 67%
2. amberlite (H+),
MeOH, 72%
HO
OH
HO
OH
HO
HO
N
N
H
Ac
OH
OH
OH
17
OH
16
Scheme 3. Synthesis of iminoheptitol 16.

1144
A. Kumar et al. / Carbohydrate Research 345 (2010) 1142–1148
MgBr
O
α-attack of
O
HO
H
OH
H
Nu:
AcO
H
O
O
H
3
4
4
3
H
H
H
2
5
HO
OH
N5
Ac
6
2
H
BnO
R
N
H
H
H
BnO
N
H
Ac
Ac
where R:
OAc
OAc
OH
17
23
Figure 3. Chelation model.
AcO
Figure 2. NOE correlations in 17 and 23.
L-allo-octitol 26, by the same sequence of reactions as described
above.
magnesium bromide in THF to give the corresponding diol, which
was acetylated using acetic anhydride in pyridine to give the diac-
etate 18 and its epimer 19 in 20:1 ratio (Scheme 4). The high dia-
stereoselectivity was presumably due to the chelation-controlled23
nucleophilic attack as shown in Figure 3. The stereochemistry was
confirmed by 1H NMR, COSY, and NOE spectral analysis of the cor-
responding pentaacetates 23 and 25, obtained later.
3. Enzyme inhibition studies
All of the prepared iminoalditols 16, 17, 24, and 26 were evalu-
ated for glycosidase inhibition activity against a few commercially
available glycosidases at millimolar concentrations (Table 1). These
compounds showed poor inhibition against b-glucosidase (entry
2). However, compound 24 showed specific inhibition of a-galacto-
Ring-closing metathesis of diene 18 with second generation
Grubbs’ catalyst B20 (3 mol %) gave the expected cyclic compound
20 in 88% yield. Dihydroxylation of 20 using a catalytic amount of
OsO4 and 2 equiv of NMO in acetone–water–t-butanol (2:2:1) at
room temperature for 12 h afforded a mixture of diastereomers,
which was separated at later stage. Thus, the crude diol, on treat-
ment with 2,2-dimethoxypropane in the presence of p-toluenesul-
fonic acid24 in acetone, formed the corresponding acetonides 21
and 22 in 1:1 ratio, which were separated by column chromatogra-
phy. Hydrogenolysis of 21 with 10% palladium hydroxide on acti-
vated carbon followed by acetylation gave the pentaacetate 23 in
89% yield. The configuration and stereochemistry of the new chiral
center was confirmed by 1H NMR, COSY, and NOE experiments.
Thus, compound 23 showed significant NOE interactions (Fig. 2)
sidase (entry 3) but again with poor inhibition.
4. Conclusions
In conclusion, this paper describes short and efficient routes for
the synthesis of 1,4-dideoxy-1,4-iminoalditols, and 1,5-dideoxy-
1,5-iminoalditols from commercially available
compounds were found to be rather poor inhibitors of glycosi-
dases. However, it is likely that structural variations of these imi-
nooctitols could lead to better/altered glycosidase inhibition.
D-xylose. These
5. Experimental section
between H-2, H-4, H-5, and H-6
aq HCl under refluxing conditions22 afforded 1,5-dideoxy-1,5-imi-
no- -threo- -galacto-octitol 24. Similarly, other isomer 22 was
converted to the desired product, 1,5-dideoxy-1,5-imino- -threo-
a
. Finally, global deprotection with
5.1. General methods and materials
D
L
The 1H NMR, NOE, and 13C spectra were recorded on a JEOL-JNM
400 MHz spectrometer. The chemical shift values are reported in
D
AcO OAc
AcO OAc
N
1.CH2=CHMgBr,
THF, -78 °C to RT
O
OH
BnO
BnO
BnO
BnO
+
N
BnO
2. Ac2O, Py, 93%
N
BnO
Ac
Ac
Ac
(20:1)
11
19
18
O
O
AcO
BnO
AcO
O
Grubbs'
AcO
BnO
O
1. OsO4, NMO, acetone /
H2O/ tBuOH (1:1: 0.5)
catalyst 'B'20
(3 mol%),
BnO
N
N
18
N
+
Ac
Ac
2. 2,2 dimethoxy propane,
TsOH, RT, 5 h, 84%
Ac
OAc
CH2Cl2, reflux
88%
OAc
OAc
21 : 22
(
= 1:1)
OBn
OBn
20
OBn
22
21
O
OH
HO
HO
AcO
OH
O
1. Pd/C, H2,12 h
1. 4N HCl, reflux,7 h
2. dowex (OH- ) resin
70%
21
AcO
2. Ac2O, Py,
20 h, 89%
N
H
N
Ac
OAc
OH
OH
OAc
AcO
23
24
OH
O
HO
HO
OH
O
1. 4N HCl, reflux, 7 h
2. dowex (OH- ) resin
71%
1. Pd/C, H2, 12 h
22
AcO
2. Ac2O, Py,
20 h, 86%
N
H
N
Ac
H+
OH
OAc
OH
OAc
26
25
Scheme 4. Synthesis of the iminooctitols 24 and 26.

A. Kumar et al. / Carbohydrate Research 345 (2010) 1142–1148
1145
OMe), 3.30 (dd, 1H, J = 13.6, 4.3 Hz, H-50). 13C NMR (100 MHz,
CDCl3): d 137.9, 137.5, 128.4, 128.3, 128.0, 127.9, 127.8, 127.7,
101.7, 79.0, 78.8, 74.8, 73.6, 72.6, 55.7, 52.6. MSES: m/z 392
[M+Na]+.
Table 1
IC50 (mM) values for compounds 16, 17, 24 and 26a
Entry
Enzyme
-Glucosidase (rice)
b-Glucosidase (almonds)
-Galactosidase (coffee beans)
b-Galactosidase (bovine liver)
-Mannosidase (jack beans)
16
17
24
26
1
2
3
4
5
a
NIb
4.2
6.7
NI
6.2
5.7
NI
NI
NI
NI
NI
3.2
NI
NI
NI
8.7
7.3
NI
a
5.2.2. N-((3S,4R,5R)-4-(Benzyloxy)-5-(benzyloxymethyl)-2-
methoxytetrahydrofuran-3-yl)acetamide (9)
a
NI
NI
To a solution of compound 8 (4.5 g, 12.2 mmol) in dry THF
(30 mL) at room temperature were added triphenylphosphine
(4.8 g, 18.3 mmol) and water (288 mg, 36.6 mmol). The mixture
was stirred for 10 h, diluted with EtOAc, washed with brine, dried
over Na2SO4, and then concentrated to give crude amine. The crude
amine was dissolved in CH2Cl2 (25 mL) and treated with pyridine
(3.0 mL), Ac2O (3.0 mL), and a catalytic amount of DMAP at room
temperature, and the mixture was stirred for 20 h. The reaction
mixture was extracted with CH2Cl2 (3 ꢀ 25 mL) and the organic
layer washed with water and brine. Evaporation of the solvent fol-
lowed by purification using SiO2 column chromatography gave 9.
Yield: 85% (4.1 g, overall yield for two steps), (colorless solid, mp
a
Inhibition studies were carried out at millimolar concentration, optimal pH of
the enzymes, and 37 °C.
b
NI: no inhibition at 3 mM concentration of the inhibitor.
parts per million (ppm) using CDCl3 as internal reference. All reac-
tions were carried out using freshly distilled and dry solvents. Col-
umn chromatography was performed over silica gel (100–200
mesh) using hexane and EtOAc as eluent. The separation of isomers
was performed on chromatotron using plates coated with Silica Gel
PF254 (E-Merck, Germany). Rotation values were recorded on an
Autopol II automatic polarimeter at the wavelength of sodium D-
line (589 nm) at 25 °C. Melting points were determined using a
Fischer-John melting point apparatus.
121–123 °C), Rf = 0.48 (hexane–EtOAc 3:2), ½a D28
ꢁ
+110.4 (c 1.05,
CH2Cl2). IR (CH2Cl2) m .
max: 3292, 3089, 2909, 1649, 1559, 1047 cmꢂ1
1H NMR (400 MHz, CDCl3): d 7.39–7.29 (m, 10H, Ar-H), 7.03 (d,
1H, J = 8.2 Hz, H-1), 4.75 (s, 1H, NH-Ac), 4.60 (d, 1H, J = 10.7 Hz,
–OCH2Ph), 4.55–4.48 (m, 3H, –OCH2Ph), 4.45 (2d, 2H, J = 3.6 Hz,
H-3, H-2), 4.43 (br d, 1H, J = 7.8 Hz, H-4), 3.81 (dd, 1H, J = 10.4,
3.1 Hz, H-5), 3.71 (dd, 1H, J = 10.7, 1.4 Hz, H-50), 3.32 (s, 3H,
OMe), 1.33 (s, 3H, NH-Ac). 13C NMR (100 MHz, CDCl3): d 137.5,
137.3, 128.4–127.6 (m, aromatic), 106.9, 77.3, 77.2, 74.1, 72.5,
68.2, 54.8, 52.7, 22.3. MSES: m/z 408 [M+Na]+.
5.2. General procedure for inhibition assay
The enzymes
a-galactosidase (coffee beans), a-glucosidases
(rice and yeast), b-galactosidase (bovine liver), b-glucosidase (al-
mond), and all the corresponding substrates were purchased from
Sigma Chemical Co. Inhibition studies of the iminoalditols 16, 17,
24, and 26 were determined by measuring the residual hydrolytic
activities of the glycosidases.
The substrate concentration (2 mM) was prepared in 0.025 M
citrate buffer with pH 4.0, and test compounds were preincubated
with the enzymes for 1 h at 37 °C. The enzyme reaction was
5.2.3. N-Allyl-N-((3S,4R,5R)-4-(benzyloxy)-5-(benzyloxymethyl)-
2-methoxytetrahydrofuran-3-yl)acetamide (10)
To the reaction mixture of 9 (4.0 g, 10.2 mmol) and allyl bro-
mide (1.3 mL, 15.3 mmol) in 20 mL dry DMF was added K2CO3
(4.14 g, 30.3 mmol) and stirred at room temperature for 4 h. After
usual work up with diethyl ether and column chromatographic
purification compound 10 was obtained. Yield: 92% (4.1 g, colorless
initiated by the addition of 100 lL substrate and the controls were
run simultaneously in the absence of the test compound. The reac-
tion was terminated at the end of 10 min by the addition of 0.05 M
borate buffer (pH 9.8) and the absorbance of the liberated p-nitro-
phenol was measured at 405 nm using a Schimadzu spectropho-
tometer UV-160A. One unit of glycosidase activity is defined as
oil). Rf = 0.50 (hexane–EtOAc 7:3), ½a D28
ꢁ
+82.6 (c 7.9, CH2Cl2). IR
m .
(CH2Cl2)
max: 3089, 2909, 1659, 1605, 1047 cmꢂ1 1H NMR
the amount of enzymes that hydrolyzed 1 lM of p-nitrophenyl
(400 MHz, CDCl3) (mixture of diastereomers): d 7.35–7.21 (m,
10H, Ar-H), 5.83–5.75 (m, 1H, –CH@CH2), 5.21 (dd, 2H, J = 12.0,
6.08 Hz, –CH@CH2), 5.03 (d, 1H, J = 1.4 Hz, H-1), 4.62 (d, 1H,
J = 11.9 Hz, –OCH2Ph), 4.52–4.46 (m, 3H, –OCH2Ph), 4.40 (d, 1H,
J = 11.6 Hz, allylic), 4.35–4.30 (m, 2H, H-4, H-3), 4.21 (m, 1H),
4.15 (m, 1H), 3.96–3.91 (dd, 1H, J = 10.7, 1.4 Hz, H-50), 3.79–3.70
(m, 3H, H-5, H-2, allylic), 3.32 (s, 3H, OMe), 2.01 (s, 3H, NH-Ac).
13C NMR (100 MHz, CDCl3): d 172.1, 137.9, 134.6, 134.4, 128.5–
127.6 (m, aromatic), 115.6, 114.4, 79.8, 78.8, 78.7, 74.4, 74.2,
73.4, 68.0, 67.5, 63.1, 55.7, 55.5, 49.5, 49.5, 48.0, 21.5. MSES: m/z
448 [M+Na]+.
pyranoside per min at 25 °C.25
5.2.1. (3S,4R,5R)-3-Azido-4-(benzyloxy)-5-(benzyloxymethyl)-2-
methoxytetrahydrofuran (8)
To a solution of compound 7 (5.0 g, 14.53 mmol) in CH2Cl2 were
added pyridine (2.9 mL, 29.0 mmol) and triflic anhydride (2.69 mL,
15.9 mmol) at 0 °C after which it was stirred at room temperature
for 20 min. When TLC revealed no starting material, the solution
was diluted with water, washed with saturated NaHCO3 (2 ꢀ 50
mL), CH2Cl2 (2 ꢀ 50 mL), brine solution (2 ꢀ 50 mL), and then dried
over Na2SO4. Removal of the solvent gave crude triflate, which was
dissolved in 40 mL of dry DMF, and sodium azide (2.83 g, 3 equiv,
43.5 mmol) was added to the solution. The reaction mixture was
heated to 70 °C for 7 h and after completion of the reaction (TLC
monitoring) it was cooled and extracted with diethyl ether
(3 ꢀ 30 mL). The extract was washed with water, brine, and dried
over anhydrous Na2SO4. Evaporation of the solvent gave a crude
product which was purified by column chromatography to give
azido compound 8 in 91% (4.9 g, oil) yield in two steps. Rf = 0.41
5.2.4. N-Allyl-N-((3S,4R,5R)-4-(benzyloxy)-5-(benzyloxymethyl)-
2-hydroxyl tetrahydrofuran-3-yl) acetamide (11)
To a solution of compound 10 (3.8 g, 8.79 mmol) in dry CH2Cl2
(20 mL) at room temperature was added triphenylcarbenium tet-
rafluroborate (2.9 g, 8.79 mmol). The mixture was stirred for 1 h
and after completion of reaction (TLC monitoring) it was quenched
with NaHCO3 and extracted with dichloromethane (3 ꢀ 20 mL) and
the organic layer washed with water and brine. Evaporation of the
solvent followed by purification using SiO2 column chromatogra-
phy gave lactol 11. Yield: 93% (3.4 g, colorless oil). Rf = 0.52 (hex-
(hexane–EtOAc 9:1), ½a D28
ꢁ
+33.6 (c 1.1, CH2Cl2). IR (CH2Cl2) mmax
:
2923, 2870, 2106, 1584, 1496 cmꢂ1
.
1H NMR (400 MHz, CDCl3): d
ane–EtOAc 2:3), ½a D28
ꢁ
+18.5 (c 1.9, CH2Cl2). IR (CH2Cl2) mmax
:
7.39–7.27 (m, 10H, Ar-H), 4.87 (d, 1H, J = 12.6 Hz, –OCH2Ph), 4.84
(d, 1H, J = 4.8 Hz, H-1), 4.73 (d, 1H, J = 12.2 Hz, –OCH2Ph), 4.63–
4.56 (2d, 2H, J = 12.2 Hz, –OCH2Ph), 4.15–4.12 (ddd, 1H, J = 8.5,
5.8, 4.1 Hz, H-4), 4.04 (t, 1H, J = 5.8 Hz, H-3), 3.82 (dd, 1H, J = 5.6,
4.4 Hz, H-2), 3.68 (dd, 1H, J = 12.9, 8.5 Hz, H-5), 3.47 (s, 3H,
3349, 2923, 2827, 1649, 1495 cmꢂ1
.
1H NMR (400 MHz, CDCl3)
(mixture of diastereomers): d 7.33–7.21 (m, 20H, Ar-H), 7.20
(d, 2H, J = 2.96 Hz, H-1), 5.81–5.75 (m, 2H, –CH@CH2), 5.54
(br s, 1H), 5.20–5.24 (m, 3H, –CH@CH2), 4.59–4.44 (m, 10H,

1146
A. Kumar et al. / Carbohydrate Research 345 (2010) 1142–1148
4 ꢀ –OCH2Ph), 4.01 (br d, 1H, J = 19.2 Hz), 3.71 (m, 3H), 1.97 (s, 6H,
NH-Ac). 13C NMR (100 MHz, CDCl3): d 171.5, 137.6, 137.3, 137.2,
133.3, 132.7, 128.5–127.5 (m, aromatic), 116.8, 116.7, 116.0,
100.0, 99.3, 95.7, 95.5, 81.6, 79.1, 78.9, 78.2, 77.9, 77.8, 77.3,
76.6, 75.8, 74.2, 73.2, 72.9, 72.5, 72.4, 72.1, 52.6, 49.2, 48.1, 47.8,
47.6, 21.7, 21.6, 21.3. MSES: m/z 434 [M+Na]+.
lytic amount of DMAP at room temperature and the mixture was
stirred for 4 h. The reaction mixture was extracted with CH2Cl2
(2 ꢀ 15 mL) and the organic layer was washed with water and
brine. Evaporation of the solvent followed by purification using
SiO2 column chromatography gave triacetate 14. Yield: 89%
(530 mg, overall yield for two steps), colorless solid, mp 141–
143 °C, Rf = 0.40 (hexane–EtOAc 2:3), ½a D28
ꢁ
+27.2 (c 1.1, CH2Cl2).
IR (CH2Cl2) m .
5.2.5. N-Allyl-N-((3S,4R,5R)-4,6-bis(benzyloxy)-5-hydroxyhex-1-
en-3-yl)acetamide (12)
max: 2922, 1744, 1653 cmꢂ1 1H NMR (400 MHz,
CDCl3): d 7.34–7.30 (m, 10H, Ar-H), 5.59 (d, 1H, J = 8.0 Hz, H-3),
5.49–5.44 (dt, 1H, J = 7.8, 4.6 Hz, H-2), 5.27–5.23 (q, 1H, J = 10.9,
5.6 Hz, H-5), 4.76 (d, 1H, J = 11.9 Hz, –OCH2Ph), 4.54 (br s, 2H, –
OCH2Ph), 4.38 (d, 1H, J = 11.9 Hz, –OCH2Ph), 4.22 (br d, 1H,
J = 5.6 Hz, H-4), 4.11 (s, 1H, H-7), 3.71–3.62 (m, 2H, H-6, H-70),
3.41 (t, 1H, J = 9.5 Hz, H-1), 3.14 (t, 1H, J = 9.2 Hz, H-10), 2.10–1.91
(3s, 9H, –OCOCH3), 1.75 (s, 3H, –NHCOCH3). 13C NMR (100 MHz,
CDCl3): d 170.3–169.5 (m), 137.8, 137.6, 128.8–127.7 (m, aro-
matic), 75.6, 74.9, 73.2, 72.4, 71.7, 70.6, 97.9, 63.5, 48.7, 22.2–
20.5 (m). HRMS calcd for C29H36NO9: [M+H]+ 542.2392, found:
542.2391.
To a stirred solution of 2.5 g (7.1 mmol) of methyltriphenyl-
phosphonium bromide in 15 mL of dry THF at 0 °C under argon
was added dropwise 1.1 mL (7.1 mmol) of 2.0 M butyllithium in
hexane during 2 min. A color change from yellow to red occurred.
The mixture was stirred for 15 min at 0 °C and a solution of 1.5 g
(3.59 mmol) of the preceding lactol in 5 mL of dry THF was added
in dropwise fashion. Solid began to form in the resulting cream col-
ored suspension. The mixture was stirred for 4 h and the reaction
was quenched by the addition of 2 mL of water. The dark brown
mixture was extracted several times with ether, and the combined
organic layers were washed with 10 mL of saturated aqueous NaCl,
and dried over anhydrous Na2SO4. Evaporation of the solvent fol-
lowed by purification using column chromatography gave diene
5.2.8. (1R,2R)-1-((2R,3S,4R)-3,4-Diacetoxy-1-acetylpyrrolidin-2-
yl)propane-1,2,3-triyl triacetate (15)
12. Yield: 92% (1.30 g, oil). Rf = 0.48 (hexane–EtOAc 3:2), ½a D28
ꢁ
To a stirred solution of triacetate 14 (300 mg, 0.55 mmol) in
ethanol (4 mL) was added 10% Pd/C (150 mg). The mixture was
stirred under hydrogen atmosphere at room temperature for
12 h. After completion of the reaction, the mixture was filtered
through a Celite pad, washed with EtOH, and the filtrate was con-
centrated under vacuo to give the corresponding diol. Acetylation
of the crude diol was done using pyridine and acetic anhydride
(1:1, 2 mL) at room temperature for 20 h. Usual workup followed
by column chromatography gave the pure pentaacetate 15. Yield:
92% (225 mg, overall yield over two steps), (oil), Rf = 0.52 (hex-
ꢂ15.3 (c 1.5, CH2Cl2). IR (CH2Cl2) mmax
: 2923, 2827, 1659,
1497 cmꢂ1 1H NMR (400 MHz, CDCl3): d 7.34–7.30 (m, 10H, Ar-
.
H), 5.94–5.86 (m, 1H, H-2), 5.78–5.75 (m, 1H, –CH@CH2), 5.46–
5.37 (dd, 2H, J = 24.6, 16.3 Hz, H-1), 5.18–5.06 (dd, 2H, J = 29.6,
16.3 Hz, –CH@CH2), 4.74 (d, 1H, J = 11.2 Hz, –OCH2Ph), 4.65–4.55
(2d, 2H, J = 11.2 Hz, –OCH2Ph), 4.43 (d, 1H, J = 11.2 Hz, –OCH2Ph),
4.16–3.96 (m, 4H), 3.54 (d, 1H, J = 14.1 Hz), 3.43–3.35 (m, 2H),
2.07 (s, 3H, NH-Ac). 13C NMR (100 MHz, CDCl3): d 171.6, 138.0,
137.2, 134.9, 133.7, 128.3–127.7 (m, aromatic), 120.3, 117.4,
78.1, 74.9, 74.4, 73.4, 73.3, 71.4, 70.8, 69.5, 61.6, 51.4, 46.3, 29.6,
22.4. MSES: m/z 432[M+Na]+.
ane–EtOAc 1:4), ½a D28
ꢁ
+16.2 (c 1.6, CH2Cl2). IR (CH2Cl2) mmax:
1744, 1653 cmꢂ1 1H NMR (400 MHz, CDCl3): d 5.56 (m, 2H, H-3,
.
H-5), 5.30 (m, 2H, H-2, H-6), 4.21 (br s, 1H, H-4), 4.17 (d, 1H,
J = 4.6 Hz, H-7), 4.05 (dd, 1H, J = 11.7, 8.0, Hz, H-7), 3.73 (dd, 1H,
J = 9.5, 7.8 Hz, H-10), 3.37 (dd, 1H, J = 9.0, 8.5 Hz, H-1), 2.14–1.98
(m, 18 H, 5 ꢀ OCOCH3 and –NHCOCH3). 13C NMR (100 MHz, CDCl3):
d 170.4–169.4 (m), 71.3, 70.2, 70.1, 69.4, 62.5, 61.7, 48.7, 22.2–20.4
(m). HRMS calcd for C19H28NO11 [M+H]+ 446.1657, found
446.1648.
5.2.6. 1-((R)-2-((1R,2R)-1,3-Bis(benzyloxy)-2-hydroxypropyl)-
2H-pyrrol-1(5H)-yl)ethanone (13)
To a stirred solution of diene 12 (600 mg, 1.46 mmol) in dry
CH2Cl2 (100 mL), the first generation Grubbs’ catalyst (60 mg,
0.050 mmol) was added. The reaction mixture was heated to reflux
under nitrogen for 14 h, then cooled, before all the solvent was evap-
orated under vacuum and the crude product was purified by column
chromatography to give cyclized product 13. Yield: 87% (495 mg,
5.2.9. (1R,2R)-1-((2R,3S,4R)-3,4-Dihydroxypyrrolidin-2-yl)
propane-1,2,3-triol (16)
oil). Rf = 0.52 (hexane–EtOAc 1:1), ½a D28
ꢁ
+26.9 (c 1.3, CH2Cl2). IR
(CH2Cl2)
m
max: 2922, 2852, 1725, 1679 cmꢂ1
.
1H NMR (400 MHz,
A solution of 15 (100 mg, 0.22 mmol) and 4 M hydrochloric acid
(2 mL) was stirred for 7 h at 80 °C and then evaporated. The residue
was purified by chromatography on a column of DOWEX basic re-
sin and concentrated under reduced pressure to get 1,4-dideoxy-
1,4-iminoheptitol 16. Yield: 67% (30 mg), light brownish solid.
CDCl3): d 7.34–7.30 (m, 10H, Ar-H), 6.04 (dd, 1H, J = 4.2, 2.2 Hz, H-
2), 5.83 (d, 1H, J = 6.3 Hz, H-3), 4.91 (br s, 1H, H-5), 4.72–4.46 (m,
5H, 2 ꢀ –OCH2Ph, H-10), 4.19 (br d, 1H, J = 14.4 Hz, H-4), 4.08 (dd,
1H, J = 14.2, 2.1 Hz, H-1), 3.97 (dd, 1H, J = 7.3, 2.9 Hz, H-6), 3.88–
3.86 (m, 1H, H-7), 3.58 (d, 1H, J = 6.0 Hz, H-1), 1.90 (s, 3H, NH-Ac).
13C NMR (100 MHz, CDCl3): d 169.9, 138.3, 137.9, 128.9–127.6 (m,
aromatic), 125.0, 124.6, 79.4, 74.9, 73.4, 71.8, 70.6, 69.2, 66.1, 64.9,
55.1, 54.6, 22.5. HRMS calcd for C23H27NO4 [M+H]+ 382.2013, found
382.1911.
½
a 2D8
ꢁ
ꢂ17.5 (c 0.8, MeOH). 1H NMR (400 MHz, D2O): d 4.32 (dd,
1H, J = 8.2, 4.1 Hz, H-3), 4.24 (br d, 1H, J = 1.7 Hz, H-2), 3.94 (t,
1H, J = 4.1 Hz, H-5), 3.75 (q, 1H, J = 6.3, 4.3 Hz, H-6), 3.59–3.57 (br
d, 1H, J = 2.2 Hz, H-4), 3.56–3.54 (d, 1H, J = 4.8 Hz, H-7), 3.51 (dd,
1H, J = 11.7, 6.6 Hz, H-70), 3.34 (dd, 1H, J = 12.9, 3.9 Hz, H-1), 3.22
(dd, 1H, J = 12.6, 1.4 Hz, H-10). 13C NMR (100 MHz, CDCl3): d 73.9,
72.9, 72.3, 70.0, 65.3, 64.9, 52.3. HRMS calcd for C7H16NO5
[M+H]+ 194.1028, found 194.1024.
5.2.7. (2S,3S,4R)-2-((1R,2R)-2-Acetoxy-1,3-bis(benzyloxy)propyl)-
1-acetylpyrrolidine-3,4-diyl diacetate (14)
To a stirred solution of an olefin 13 (450 mg, 1.18 mmol) in ace-
tone–water–t-butanol (1:1:0.4) at room temperature were added
5.2.10. 1-((2R,3S,4R)-3,4-Dihydroxy-2-((1R,2R)-1,2,3-trihydroxy-
propyl)pyrrolidin-1-yl)ethanone (17)
NMOꢃH2O (151 mg, 1.29 mmol) and OsO4 (576
lL, 0.002 equiv).
The reaction mixture was stirred for 14 h and it was treated with
Na2S2O5 (430 mg, 1.18 mmol). The reaction mixture was further
stirred for 1 h and extracted with EtOAc (2 ꢀ 30 mL). The organic
layer was washed with 1 N HCl, water, and finally with brine. Usual
workup gave a crude product, which was dissolved in CH2Cl2
(7 mL) and treated with pyridine (1 mL), Ac2O (1 mL), and a cata-
Deacetylation of the pentaacetate 15 was done using NaOMe in
MeOH at room temperature. The crude product was filtered
through Amberlite (H+) ion exchange resin for the enzyme inhibi-
tion studies. Yield: 72%. ½a D28
ꢁ
+27.5 (c 0.9, MeOH). 1H NMR
(400 MHz, D2O) (mixture of rotamers): d 4.35 (dd, 1H, J = 8.7,
3.6 Hz, H-2), 4.27 (dd, 1H, J = 7.5, 3.4 Hz, H-3), 4.09 (t, 1H,

A. Kumar et al. / Carbohydrate Research 345 (2010) 1142–1148
1147
J = 4.1 Hz, H-3, minor rotamer), 4.00 (m, 1H, H-2, minor rotamer),
3.80 (dd, 1H, J = 8.0, 4.8 Hz, H-4), 3.75 (dd, 1H, J = 8.5, 3.6 Hz, H-
5), 3.65 (dd, 1H, J = 10.7, 4.4 Hz, H-1), 3.60–3.52 (m, 3H, H-6,
2 ꢀ H-7), 3.39 (dd, 1H, J = 11.2, 5.6 Hz, H-10). 13C NMR (100 MHz,
D2O): d 176.6, 74.0, 73.3, 72.4, 71.6, 69.2, 67.5, 65.1, 54.7, 53.7,
53.2, 24.1. HRMS calcd for C9H18NO6 [M+H]+ 236.1129, found
236.1053.
4H), 3.20 (dd, 1H, J = 14.0 Hz, rotamer-II), 2.08–1.98 (m, 18 H,
6 ꢀ –COCH3). 13C NMR (100 MHz, CDCl3): d 170.3–169.5 (m),
137.7, 137.3, 136.9, 130.9, 128.7–127.8 (m, aromatic), 122.5,
121.1, 74.9, 74.3, 73.4, 71.1, 70.7, 76.1, 66.3, 65.6, 56.8, 49.7,
42.7, 38.5, 21.8–20.8 (m). HRMS calcd for C28H33NNaO7 [M+Na]+
518.2155, found 518.2150.
5.2.14. (3aS,6R,7R,7aS)-6-((1R,2R)-2-Acetoxy-1,3-bis(benzyloxy)-
propyl)-5-acetyl-2,2-dimethylhexa-hydro-[1,3]dioxolo[4,5-c]-
pyridin-7-yl acetate (21)
5.2.11. (2R,3R,4S,5R)-4-(N-Allylacetamido)-1,3-bis(benzyloxy)
hept-6-ene-2,5-diyl diacetate (18)
To a stirred solution of lactol 11 (1.50 g, 3.59 mmol) in dry THF
(20 mL) was added dropwise vinyl magnesium bromide (2.87 mL,
21.54 mmol, 1.0 M solution in THF) at ꢂ78 °C, and the reaction
mixture was stirred at 0 °C for 3 h. The reaction was quenched with
saturated NH4Cl solution and the aqueous phase of the mixture
was extracted with EtOAc (3 ꢀ 20 mL). The combined organic ex-
tracts were dried over anhydrous MgSO4 and filtered. The filtrate
was concentrated under reduced pressure to get oil. Acetylation
of the diol was done using pyridine and acetic anhydride (1:1,
4 mL) at room temperature for 10 h. Usual workup followed by col-
umn chromatography afforded first diene 18 (89%, 1.67 g) and sec-
To a stirred solution of an olefin 20 (1.61 mmol) in acetone–
water–t-butanol (1:1:0.4) at room temperature were added
NMOꢃH2O (188 mg, 1.61 mmol) and OsO4 (710
lL, 0.002 equiv).
The reaction mixture was stirred for 12–14 h (monitored by TLC)
and it was treated with Na2S2O5 (296 mg, 1.77 mmol). The reaction
mixture was further stirred for 1 h and extracted with EtOAc
(2 ꢀ 20 mL). The organic layer was washed with 1 N HCl, water,
and finally with brine. Usual workup gave the crude diol which
was dissolved in CH2Cl2 (5 mL) and then treated with 2,2-dime-
thoxypropane (1.0 mL, 8.05 mmol) and catalytic amount of p-tolu-
enesulfonic acid at room temperature. The reaction mixture was
stirred for 5 h and progress of the reaction was monitored by
TLC. Evaporation of the solvent gave a residue, which was purified
by column chromatography to give two separable diastereomers
21 and 22. Data for 21: Yield: 41% (375 mg), colorless solid, mp
ond its epimer 19 (4%, 80 mg) as colorless oils. Data for 18: ½a D28
ꢁ
+19.1 (c 1.1, CH2Cl2). Rf = 0.50 (hexane–EtOAc 7:3). IR (CH2Cl2)
m
max: 2803, 1734, 1659, 1632 cmꢂ1 1H NMR (400 MHz, CDCl3): d
.
7.40–7.24 (m, 10H, Ar-H), 6.01 (br m, 1H, –CH@CH2), 5.70–5.66
(m, 1H, H-2), 5.57 (br t, 1H), 5.49 (d, 1H, J = 16.8 Hz), 5.29–5.15
(m, 4H, H-1, –CH@CH2), 5.08 (d, 1H, J = 17.8 Hz), 4.70 (d, 1H,
J = 10.9 Hz, –OCH2Ph), 4.57–4.51 (2d, 3H, J = 11.2 Hz, –OCH2Ph),
4.30 (br d, 1H, J = 8.0 Hz), 4.15 (br d, 1H, J = 10.2 Hz), 3.91 (t, 1H,
J = 8.7 Hz), 3.85 (d, 1H, J = 11.9 Hz), 3.66 (dd, 1H, J = 11.2, 1.9 Hz),
2.06 (s, 6H, OCOCH3), 1.93 (s, 3H, NHCOCH3). 13C NMR (100 MHz,
CDCl3): d 170.3–169.4 (m) 144.3, 138.5, 138.1, 133.9, 133.5,
128.3–126.7, 120.9, 112.4, 76.3, 75.4, 73.9, 72.3, 71.5, 68.6, 68.2,
22.9, 21.1, 15.0. HRMS calcd for C30H37NNaO7 [M+Na]+ 546.2463,
found 546.2469.
114–116 °C; Rf = 0.42 (hexane–EtOAc, 3:2), ½a D28
ꢁ
+66.6 (c 0.2,
CH2Cl2). IR (CH2Cl2) m .
max: 2922, 2852, 1735, 1679 cmꢂ1 1H NMR
(400 MHz, CDCl3) (mixture of rotamers): d 7.36–7.24 (m, 20H,
Ar-H, for both), 5.60 (t, 1H, J = 5.1 Hz, major rotamer), 5.40 (m,
1H, H-3, minor rotamer), 5.20 (q, 1H, J = 5.6, 1.9 Hz, H-6), 4.85 (t,
1H, J = 5.1 Hz, H-2), 4.75 (t, 1H, J = 5.1 Hz, H-2, minor rotamer),
4.68–4.47 (m, 6H, both rotamers), 4.33 (dd, 1H, 1H, J = 7.5,
4.1 Hz), 4.25–4.19 (m, 4H, both rotamers), 3.93 (br d, 1H,
J = 8.5 Hz, minor rotamer), 3.71–3.60 (m, 5H), 3.21 (d, 1H, 1H,
J = 12.1 Hz, minor rotamer), 2.95 (d, 1H, J = 12.1 Hz, minor rot-
amer), 2.09–1.92 (m, 18H, 6 ꢀ –COCH3), 1.38 (2s, 6H, –CH3, both
rotamers), 1.27 (2s, 6H, –CH3, both rotamers). 13C NMR
(100 MHz, CDCl3): d 170.3–169.9 (m), 138.7, 137.8, 129.4–127.0
(m, aromatic), 110.1, 109.4, 81.4, 79.4, 78.8, 75.4, 73.3, 72.8, 72.4,
71.7, 69.3, 68.7, 67.3, 51.7, 50.7, 45.7, 29.6, 27.0, 25.8, 25.7, 24.3,
24.0, 22.6, 21.7–21.0 (m). HRMS calcd for C31H40NO9 [M+H]+
570.2703, found 570.2631.
5.2.12. (2R,3R,4S,5S)-4-(N-Allylacetamido)-1,3-bis(benzyloxy)
hept-6-ene-2,5-diyl diacetate (19)
½
a 2D8
(CH2Cl2)
ꢁ
+22.1 (c 0.8, CH2Cl2). Rf = 0.49 (hexane–EtOAc 7:3). IR
m
max: 2903, 1744, 1659, 1642 cmꢂ1 1H NMR (400 MHz,
.
CDCl3): d 7.38–7.25 (m, 10H, Ar-H), 5.95 (m, 1H, –CH@CH2), 5.72
(m, 1H, H-2), 5.57 (t, 1H, J = 5.6 Hz), 5.17–5.03 (m, 5H, H-4, H-1,
–CH@CH2), 4.27 (d, 1H, J = 11.2 Hz, –OCH2Ph), 4.57–4.51 (m, 4H,
3 ꢀ –OCH2Ph), 4.35 (br d, 1H, J = 7.0 Hz), 4.19–4.17 (m, 1H), 3.96–
3.82 (m, 2H), 3.65 (d, 1H, J = 11.4 Hz), 2.06 (s, 6H, 2 ꢀ –OCOCH3),
1.95 (s, 3H, NHCOCH3). 13C NMR (100 MHz, CDCl3): d 170.3–
169.4 (m) 144.3, 138.5, 138.1, 133.9, 133.5, 128.3–126.7 (m, aro-
matic), 120.9, 112.4, 76.3, 75.4, 73.9, 72.3, 71.5, 68.6, 68.2, 22.9,
21.1, 15.0. HRMS calcd for C30H37NNaO7 [M+Na]+ 546.2648, found
546.2469.
5.2.15. (3aR,6R,7R,7aR)-6-((1R,2R)-2-Acetoxy-1,3-bis(benzyloxy)-
propyl)-5-acetyl-2,2-dimethylhexa hydro-[1,3]dioxolo[4,5-c]
pyridin-7-yl acetate (22)
Data for 22: Yield: 43% (395 mg), colorless liquid. Rf = 0.40 (hex-
ane–EtOAc 3:2), ½a D28
ꢁ
ꢂ5.2 (c 1.2, CH2Cl2). IR (CH2Cl2)
mmax: 2922,
2852, 1735, 1679 cmꢂ1
.
1H NMR (400 MHz, CDCl3) (mixture of
rotamers): d 7.41–7.30 (m, 20H, Ar-H, for both), 5.68–5.63 (m,
2H, for both), 4.99–4.93 (m, 2H), 4.84 (d, 1H, J = 11.0 Hz), 4.66–
4.46 (m, 5H), 4.27 (m, 2H), 4.13 (m, 1H), 3.77–3.51 (m, 3H), 2.93
(dd, 1H, J = 14.4, 10.4 Hz), 2.09–1.97 (m, 18H, 6 ꢀ –COCH3), 1.38
(s, 3H, –CH3, major rotamers), 1.37 (s, 3H, –CH3, minor rotamers),
1.32 (2s, 6H, –CH3, both rotamers). 13C NMR (100 MHz, CDCl3): d
170.3–169.4 (m), 137.9, 137.7, 128.4–127.7 (m, aromatic), 110.0,
109.8, 75.2, 74.3, 73.9, 73.6, 72.6, 70.5, 69.3, 68.4, 67.6, 67.0,
66.7, 57.2, 50.3, 43.9, 38.4, 29.6, 28.0, 26.1, 26.0, 24.1, 21.9, 21.8,
20.8, 20.6. HRMS calcd for C31H39NNaO9 [M+Na]+ 592.2523, found
592.2540.
5.2.13. (2R,3R)-2-((1S,2R)-2-Acetoxy-1,3-bis(benzyloxy)propyl)-
1-acetyl-1,2,3,6-tetrahydropyridin-3-yl acetate (20)
Compound 20 (890 mg) was obtained from 18 (1.0 g,
1.91 mmol) using the procedure which was used to obtain 13.
Yield: 88%, colorless syrup, Rf = 0.40 (hexane–EtOAc 2:3). ½a D28
ꢁ
ꢂ74.8 (c 3.7, CH2Cl2). IR (CH2Cl2) mmax
: 2922, 2852, 1725,
1679 cmꢂ1 1H NMR (400 MHz, CDCl3) (mixture of rotamers): d
.
7.34–7.30 (m, 20H, Ar-H, both rotamers), 5.95–5.90 (ddd, 2H,
J = 5.8, 3.8, 2.2 Hz, H-2, both rotamers), 5.81 (br dd, 2H, J = 5.8,
3.8, 2.2 Hz, H-2, both rotamers), 5.41 (dd, 2H, J = 11.2, 5.6 Hz, H-
4, both rotamers), 5.17 (d, 1H, J = 9.7 Hz, rotamer-II), 4.99–4.93
(m, 2H, H-10, both rotamers), 4.67 (2d, 2H, J = 11.2 Hz, –OCH2Ph,
both rotamers), 4.55–4.47 (m, 8H, –OCH2Ph, both rotamers), 4.29
(d, 1H, J = 9.5 Hz, rotamer-II), 4.10 (br d, 1H, J = 19.7 Hz, rotamer-
II), 3.88 (dd, 2H, J = 10.2, 2.2 Hz, both rotamers), 3.69–3.58 (m,
5.2.16. (1R,2R)-1-((3aS,6S,7S,7aS)-7-Acetoxy-5-acetyl-2,2-
dimethyl-hexahydro-[1,3]dioxolo[4,5-c]pyridin-6-yl)propane-
1,2,3-triyl triacetate (23)
This compound was prepared in 89% yield from 21 by using the
same procedure as described for 15. Yield: 89% (overall yield in two

1148
A. Kumar et al. / Carbohydrate Research 345 (2010) 1142–1148
steps). Rf = 0.52 (hexane–EtOAc 2:3), ½a D28
ꢁ
+36.6 (c 0.75, CH2Cl2). IR
Supplementary data
(CH2Cl2) m .
max: 1743, 1657 cmꢂ1 1H NMR (400 MHz, CDCl3): d 5.54
(dd, 1H, J = 5.6, 3.9 Hz, H-3), 5.35 (dd, 1H, J = 5.6, 3.9 Hz, H-3), 5.22
(dd, 1H, J = 9.5, 5.6 Hz, H-4), 5.01–4.98 (ddd, 1H, J = 8.0, 5.8, 1.9 Hz,
H-7), 4.32–4.26 (m, 2H, H-2, H-6), 4.23 (dd, 1H, J = 11.6, 5.6 Hz, H-
8), 3.91 (dd, 1H, J = 10.2, 6.3 Hz, H-80), 3.81 (d, 1H, J = 15.3 Hz, H-1),
3.51 (d, 1H, J = 15.3 Hz, H-10), 2.19–2.13 (2s, 6H, 2 ꢀ –COCH3),
2.07–2.00 (3s, 9H, 3 ꢀ –COCH3), 1.37 (s, 3H, –CH3), 1.28 (s, 3H, –
CH3). 13C NMR (100 MHz, CDCl3): d 172.6–169.5 (m), 110.4, 72.4,
71.5, 68.5, 68.2, 66.2, 62.4, 48.2, 44.9, 25.3, 24.0, 21.8, 21.0, 20.6.
HRMS calcd for C21H31NNaO11 [M+Na]+ 496.1795, found 496.1792.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.04.016.
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5.2.17. (2S,3S,4S,5S)-2-((1R,2R)-1,2,3-Trihydroxypropyl)
piperidine-3,4,5-triol (24)
This compound was prepared in 70% yield from 23 by using the
same procedure as described for 16. Yield: 70% (50 mg), colorless
solid, mp 121–123 °C. ½a D28
ꢁ
ꢂ20.0 (c 0.1, H2O). 1H NMR (400 MHz,
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d 73.5, 72.2, 70.5, 69.5, 68.8, 66.0, 63.5, 58.4, 58.4,
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NMR (400 MHz, CDCl3): d 5.81 (dd, 1H, J = 9.7, 2.2 Hz, H-6), 5.23
(t, 1H, J = 2.9 Hz, H-4), 5.14–5.12 (ddd, 1H, J = 8.0, 6.6, 2.2 Hz,
H-7), 4.93 (br d, 1H, J = 9.8 Hz, H-5), 4.29–4.20 (m, 2H, H-8, H-2),
4.09 (dd, 1H, J = 4.9, 3.4 Hz, H-3), 3.88–3.82 (m, 2H, H-80, H-10),
3.01–2.95 (dd, 1H, J = 14.6, 10.4 Hz, H-1), 2.23 (s, 3H, –COCH3),
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74.4, 69.3, 68.4, 67.9, 67.4, 66.9, 62.1, 49.5, 44.1, 28.0, 25.9, 21.1,
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5.2.19. (2S,3S,4R,5R)-2-((1R,2R)-1,2,3-Trihydroxypropyl)
piperidine-3,4,5-triol (26)
Compound 26 (33 mg) was obtained from 25 (100 mg,
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ꢁ
ꢂ13.1 (c 0.3, H20). 1H
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(100 MHz, D2O): d 74.2, 72.5, 67.6, 67.4, 67.2, 63.8, 61.1, 49.3.
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Acknowledgments
We thank the Department of Science and Technology, New
Delhi, for financial support to Y.D.V. in the form of Ramanna
Fellowship (Grant No. SR/S1/RFOC-04/2006). A.K. thanks Council
of Scientific and Industrial Research for senior research
fellowships.