(3S,4R,5R)-3-(2-Hydroxyethyl)piperidine-3,4,5-triol as an isofagomine analogue: Synthesis and glycosidase inhibition study

Article abstract of DOI:10.1016/j.tetasy.2010.11.027

The synthesis of (3S,4R,5R)-3-(2-hydroxyethyl)piperidine-3,4,5-triol 10 has been described from d-glucose. The base promoted cyclization for the construction of the piperdine framework is the key step of the synthesis.

Full text of DOI:10.1016/j.tetasy.2010.11.027

Tetrahedron: Asymmetry 21 (2010) 2966–2972
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Tetrahedron: Asymmetry
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(3S,4R,5R)-3-(2-Hydroxyethyl)piperidine-3,4,5-triol as an isofagomine
analogue: synthesis and glycosidase inhibition study
⇑
Preeti Gupta, Suresh Dharuman, 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 (3S,4R,5R)-3-(2-hydroxyethyl)piperidine-3,4,5-triol 10 has been described from D-glu-
cose. The base promoted cyclization for the construction of the piperdine framework is the key step of
the synthesis.
Received 2 November 2010
Accepted 26 November 2010
Available online 11 January 2011
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
8 with a hydroxyethyl chain at C-4, which was found to be specific
and potent inhibitor against b-glucosidase. Similarly, Takahata
Azasugars (or iminosugars) are sugar-mimics with a nitrogen in
place of the ring oxygen, and have attracted a great deal of attention
as inhibitors of carbohydrate processing enzymes such as glycosi-
dases and glycosyl transferases.1 Since the discovery of 1-deoxynoj-
et al.14 have reported the synthesis of homoisofagomine 9.
Continuing our interest toward the design, synthesis, and
biological evaluation of natural and unnatural azasugars and hybrid
molecules as glycosidase inhibitors,15 we have synthesized
(3S,4R,5R)-3-(2-hydroxyethyl)piperidine-3,4,5-triol 10 from readily
irimycin 1 (DNJ), a potent a-glucosidase inhibitor, research efforts
have been directed toward the synthesis and biological evaluation
of naturally occurring and synthetic azasugars.2 In view of their
promising inhibition profile, azasugars are now finding clinical
applicationsas antidiabetic,3 anticancer,4 anti-HIV,5 and therapeutic
agents for some genetic disorders.6 N-Butyl-DNJ (Miglustat) 2 and
N-hydroxyethyl-DNJ (Miglitol) 3 have already been approved for
thetreatmentof typeI Gaucher’sdiseaseandtypeII diabetes, respec-
tively. Galacto-DNJ 4 has demonstrated inhibition of lysosomal
available and inexpensive D-glucose. The design was conceived from
the view that a pendant hydroxyethyl substituent at C-3 along with
the hydroxyl group may impart selective and/or improved inhibi-
tion, as has been observed in the literature.13,16
2. Results and discussion
The synthesis emanated from diol 14 (Scheme 1), which was
obtained from D-glucose in four steps by following the literature
a-galactosidase and is currently in phase B clinical trials for the
treatmentof Fabry’sdisease(Fig. 1).7 Thesearchfor anomerselective
b-glycosidase inhibitors has led to a new class of sugar-mimics,
1-N-iminosugars or 1-azasugars with a nitrogen atom at the
anomeric position. The representative 1-N-azasugar isofagomine 5
was first designed by Bols et al.8 as an apparent transition state
analog mimicking the carbocationic form of the oxycarbenium-like
transition state in which the positive charge resides at the anomeric
carbon. Isofagomine has been found to be a selective and very strong
procedures.17–19 The regioselective protection of the primary alco-
hol in 14 as trityl ether provided 15 in 90% yield. Dihydroxylation
of 15 with OsO4–NMO followed by sodium periodate oxidation
afforded the corresponding aldehyde, which upon sodium borohy-
dride reduction furnished diol 16 in 80% yield. Protection of both
the hydroxyl groups in 16 as benzyl ethers using sodium hydride
and benzyl bromide provided 17 in excellent yield. Detritylation in
17usingHClO4ꢀSiO2, a proceduredeveloped inour laboratory,20 gave
alcohol 18 in 92% yield. Mesylation of the primary alcohol followed
by nucleophilic displacement with sodium azide in DMF furnished
the azido compound 20 in good yield. The IR spectrum of 20 showed
a strong absorption peak at 2101 cmꢁ1, confirming the presence of
an azide group. Cleavage of the 1,2-acetonide functionality in 20
using TFA–H2O (1:1) followed by sodium periodate oxidation affor-
ded the desired aldehyde 21 in 88% yield. Compound 21, in its 1H
NMR spectrum, showed characteristic peaks at d 8.17 for the –OCHO
group and at d 9.38 for the –CHO group. Similarly, in the 13C NMR
spectrum of 21, an oxycarbonyl signal appeared at d 159.2 while
the carbonyl signal of the –CHO appeared downfield at d 199.5. Its
inhibitor of b-glucosidase [Ki = 0.11 l
M, sweet almonds]8,9 and its
2-hydroxy analog noeuromycin 6 shows b-glucosidase inhibition
in the nanomolarrange.10 Similarly, isogalactofagomine 7 was found
to be
[Ki = 0.004
a
selective and potent inhibitor for b-galactosidases
M, Aspergillus oryzae].11 Due to the pronounced and
l
selective inhibition activities of isofagomine and its congeners, there
has been an increased interest toward the synthesis of such 1-N-imi-
nosugars.12 Dhavaleet al.13 havereportedthesynthesisofpiperidine
⇑
Corresponding author. Tel.: +91 512 2597169; fax: +91 512 259 0007.
E-mail address: vankar@iitk.ac.in (Y.D. Vankar).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.11.027

P. Gupta et al. / Tetrahedron: Asymmetry 21 (2010) 2966–2972
2967
reaction was not clean, and led to the formation of a mixture of prod-
ucts. Next, the treatment of azide 21 with Pd/CaCO322 in MeOH in the
presence of H2 (1 atm) at room temperature followed by reductive
amination withsodium cyanoborohydride gavethecyclizedproduct
albeit in poor yield.
R
N
H
N
H
N
HO
HO
HO
HO
HO
OH
HO
OH
OH
OH
OH
OH
Hence, we explored a different pathway and instead of perform-
ing the direct cyclization, we attempted the base promoted cycliza-
tion for obtaining the desired piperidine framework. Thus,
reduction of aldehyde 21 with sodium borohydride in methanol
furnished the diol 22 in 83% yield (Scheme 2). The disappearance
of the corresponding –OCHO and the –CHO group signals in the
1H and 13C NMR spectrum of 21 and presence of characteristic
absorptions at 3433 cmꢁ1 for –OH and 2100 cmꢁ1 for an azide
group in its IR spectrum indicated its azido alcohol structure. Reg-
ioselective protection of the primary alcohol in 22 as a trityl ether
and secondary alcohol as benzyl ether gave compound 24. How-
ever, trityl cleavage in 24 employing HClO4ꢀSiO2 was unsuccessful
and whole starting material was recovered back from the reaction.
Thereby, detritylation in 24 was carried out by using TFA/CH2Cl2
which gave the alcohol 25 without affecting the azide moiety.
The IR spectrum of 25 showed a broad peak at 3442 cmꢁ1 for –OH
stretching and a strong absorption peak at 2099 cmꢁ1 for the azide
group. The reaction of the hydroxyl group with methanesulfonyl
chloride, Et3N, and a catalytic amount of DMAP furnished the
mesylated derivative 26.
2
R = nBu
4
1
3 R = CH2CH2OH
H
N
H
H
N
N
OH
OH
OH
OH
OH
OH
OH OH
OH OH
OH OH
7
5
6
H
N
H
N
H
N
HO
HO
HO
OH
OH
OH
10
HO
OH
9
8
Figure 1. DNJ, isofagomine and its derivatives.
IR spectrum also showed strong absorption peaks at 2105 and
1736 cmꢁ1 for the azide and carbonyl groups, respectively. The azido
aldehyde 21 thus obtained was now ready for cyclization. However,
the one pot reaction21 of azide reduction, reductive amination, and
debenzylation using 20% Pd(OH)2/C under hydrogenation condition
in methanol was unsuccessful in giving the desired product. This
The next step of the synthesis was the formation of the piperi-
dine ring. For this, azide 26 was reduced to the corresponding
amine using Ph3P in THF–H2O (9:1) at room temperature. How-
ever, cyclization of the crude amine with Et3N in refluxing metha-
nol followed by Boc protection provided the cyclized compound 28
O
O
O
O
O
O
ref. 19
ref. 17
ref. 18
O
O
D
-Glucose
O
O
HO
OR
11
12 R =H
13 R= OBn
ref. 19
TrO
HO
TrO
HO
HO
HO
O
O
O
O
i
ii
iii
O
O
O
O
O
OBn
OBn
OBn
14
HO
16
15
MsO
BnO
HO
TrO
O
O
O
O
iv
BnO
vi
BnO
v
O
O
O
O
O
OBn
OBn
18
OBn
17
BnO
BnO
BnO
19
N3
OCHO
O
BnO
vii
O
N3
O
OBn
BnO
O
OBn
BnO
BnO
20
21
Scheme 1. Reagents and conditions: (i) TrCl, Et3N, CH2Cl2, 0 °C to rt, overnight, 90%; (ii) (a) OsO4, NMO, acetone/water/tBuOH (1:1:0.5), rt, 12 h; (b) NaIO4, MeOH/H2O (9:1),
0 °C, 30 min; (c) NaBH4, MeOH, 0 °C to rt, 2 h, 80% (over three steps); (iii) NaH, BnBr, DMF, 0 °C to rt, overnight, 96%; (iv) HClO4ꢀSiO2, MeOH, rt, 3 h, 92%; (v) MsCl, Et3N, CH2Cl2,
0 °C, 1 h, 95%; (vi) NaN3, DMF, 120 °C, 3 h, 85%; (vii) (a) TFA/H2O (1:1), rt, 1 h; (b) NaIO4, MeOH/H2O (9:1), 0 °C to rt, 8 h, 88%.

2968
P. Gupta et al. / Tetrahedron: Asymmetry 21 (2010) 2966–2972
OH
OH
i
ii
iii
N3
OH
OBn
N3
OTr
OBn
21
BnO
BnO
BnO
BnO
23
22
OBn
OBn
BnO
OBn
iv
vi
BocHN
OMs
OBn
N3
OR
OBn
N3
OTr
OBn
BnO
BnO
v
BnO
BnO
BnO
24
25
26
R = H
R = OMs
27
H6
H4
H2
Boc
N
H
N
vii
viii
H6'
H5
H2'
N
OBn
OH
OH
BnO
HO
OH
OH
OH
OBn
OH
OBn
OH
10
28
Scheme 2. Reagents and conditions: (i) NaBH4, MeOH, 0 °C to rt, overnight, 83%; (ii) TrCl, Et3N, CH2Cl2, 12 h, 77%; (iii) NaH, BnBr, DMF, 0 °C, 2 h, 97%; (iv) TFA, CH2Cl2, 0 °C,
30 min, 81%; (v) MsCl, Et3N, CH2Cl2, 0 °C, 1 h, 97%; (vi) (a) Ph3P, THF/H2O (9:1), rt, 8 h; (b) Boc2O, NaHCO3, EtOAc, 0 °C to rt, overnight, 81%; (vii) NaH, THF, reflux, 4 h, 75%;
(viii) (a) Pd(OH)2/C, H2, 20 psi, rt, 12 h; (b) 6 M HCl, MeOH, rt, 12 h; (c) Dowex OHꢁ quantitative yield.
in poor yield (25%) along with an unidentifiable product. Cycliza-
tion using K2CO3/CH3CN23 instead of Et3N/MeOH24 did not lead
to any significant improvements in the yield of 28. Consequently,
we changed the reaction sequence to obtain the desired piperidine.
The reduction of the azide in 26 with Ph3P provided the corre-
sponding free amine, which upon treatment with di-tert-butylpy-
rocarbonate afforded the Boc protected amine 27 in 81% yield
over two steps. Reaction of amine 27 with tBuOK (2 equiv) in
THF provided the cyclized product 28 in only 15% yield along with
recovered starting material. Increasing the base equivalents led to
the formation of side products. Treatment of the amine 27 with
NaH (2 equiv) in THF under refluxing conditions produced the de-
sired Boc protected piperidine 28 in 75% yield. The 1H NMR spec-
Compound 10 was a very weak galactosidase inhibitor [IC50 =
5.0 mM]. It is expected that further structural modifications may
lead to improved inhibitions.
4. Experimental
Infrared spectra were recorded with a Bruker FT/IR Vector 22
spectrometer. 1H and 13C NMR spectra were recorded with a JEOL
LA-400 (400 and 100 MHz, respectively) or JEOL ECX-500 spec-
trometer (500 and 125 MHz, respectively) in solutions of CDCl3
using tetramethylsilane as the internal standard. Chemical shifts
are reported in ppm downfield to tetramethylsilane. Coupling con-
stants are reported in Hz and splitting patterns are expressed as s
(singlet), d (doublet), dd (doublet of doublets), m (multiplet), and
br s (broad singlet). The mass spectra were recorded with a
Waters HAB 213 Q Tof Premier Micromass. Optical rotations were
recorded with an Autopol II automatic polarimeter at the wave-
length of the sodium D line (589 nm) at 25 °C. Column chromatog-
raphy was performed on silica gel (100–200 mesh) using hexane
and ethyl acetate as eluents. Thin-layer chromatography (TLC)
was performed on silica gel plates made by using grade G silica
gel obtained from s.d.fine-chem Ltd, Mumbai, or on Merck silica
gel precoated on plastic plates. All solvents and common reagents
were purified by established procedures.
trum of compound 28 showed
a broadening of the signals
indicating that it was a mixture of rotamers. However, the diappea-
rence of signals corresponding to the –SO2CH3 protons confirmed
the cyclization. Cyclization was further confirmed from the mass
spectrum HRMS [M+H]+ peak at 638.3482 [expected 638.3481]. Fi-
nally, deprotection of the benzyl groups with 20% Pd(OH)2/C–H2 in
methanol at 20 psi followed by treatment with 6 M HCl allowed
the removal of the NHBoc protecting group, which after passing
through a basic Dowex column afforded the fully deprotected com-
pound 10 in almost quantitative yield. Compound 10 was well
characterized by 1H, 13C NMR, as well as by mass spectrometry
studies. In the 1H NMR spectrum of 10, the appearance of two
broad doublets at d 2.95 and 2.77 (J6a,6e = 13.7 Hz) corresponding
to protons H-6 and H-60 suggested that H-5 is equatorially oriented
and bisects the H-6 protons (dihedral angle ꢂ55°). The H-5 proton
also appeared as broad singlet at d 3.87 thus indicating the 2C5 con-
formation in 10. The inhibitory activity of compound 10 was tested
against four commercially available glycosidases at millimolar con-
centration. However it was only active against b-galactosidase
(Aspergillus oryzae) with IC50 = 5.0 mM.25
4.1. General procedure (A): Tritylation of the primary alcohol
To a stirred solution of diol (1 mmol) in CH2Cl2 (10 mL) at 0 °C
were added Et3N (3 mmol), TrCl (1.2 mmol), and a catalytic
amount of DMAP. The reaction mixture was stirred for 8–10 h at
room temperature and then usual work-up by CH2Cl2 and water
gave a crude product, which was purified by column chromatogra-
phy to give the pure tritylated compounds.
3. Conclusions
4.2. General procedure (B): Benzylation of the alcohol
In conclusion, we have reported the synthesis of the 1-N-imino-
At first, 60% suspension of NaH in paraffin oil (1.2 mmol) was
added portionwise to a stirred solution of the alcohol (1 mmol)
sugar 10 from inexpensive and readily available
D-glucose.

P. Gupta et al. / Tetrahedron: Asymmetry 21 (2010) 2966–2972
2969
in DMF (10 mL) at 0 °C. After 30 min, benzyl bromide (1.2 mmol)
was added dropwise at 0 °C and the reaction mixture was stirred
for 2–4 h at room temperature. Excess NaH was quenched by pour-
ing the reaction mixture onto ice and then extracted with diethyl
ether (30 mL) followed by washing with water and brine solution.
The organic layer was dried with anhydrous Na2SO4, concentrated
in vacuo and the crude product, purified by column chromatogra-
phy to give benzylated products.
phase was extracted with ethyl acetate and the combined organic
extracts were washed with water and brine and dried with anhy-
drous Na2SO4. Purification through column chromatography fur-
nished the pure compound 16 (1.2 g, 80%) as a colorless liquid.
Rf = 0.5 (hexane/EtOAc, 1:1). ½a D25
ꢄ
¼ þ3:8 (c 1.5, CH2Cl2). IR (neat)
m
max: 3400, 2927, 1073, 1020 cmꢁ1 1H NMR (400 MHz, CDCl3): d
.
7.48–7.42 (m, 6H, ArH), 7.38–7.18 (m, 14H, ArH), 5.61 (d, 1H,
J = 3.6 Hz), 4.78 (s, 2H, –OCH2Ph), 4.54 (d, 1H, J = 3.6 Hz), 4.40 (d,
1H, J = 9.2 Hz), 3.83–3.79 (m, 3H), 3.36–3.29 (m, 2H), 2.80 (br s,
1H, –OH), 2.60 (br s, 1H, –OH), 2.10–2.03 (m, 1H), 1.89–1.84 (m,
1H), 1.56 (s, 3H, –C(CH3)2), 1.33 (s, 3H, –C(CH3)2) ppm. 13C NMR
(125 MHz, CDCl3): d 144.0, 138.6, 128.8, 128.6, 128.4, 128.0,
127.9, 127.6, 127.1, 127.0, 112.9, 103.5, 86.7, 84.7, 83.5, 69.3,
67.6, 65.5, 58.4, 33.5, 26.9, 26.7 ppm. HRMS (ESI): calcd for
4.3. General procedure (C): Mesylation of the primary alcohol
To a stirred solution of alcohol (1 mmol) in CH2Cl2 (10 mL) at
0 °C were added Et3N (1.5 mmol), followed by the slow addition
of methanesulfonyl chloride (1.2 mmol) and a catalytic amount
of DMAP. The reaction mixture was stirred for 1 h at 0 °C (TLC
monitoring) and then quenched by the addition of saturated NaH-
CO3 solution (10 mL). The mixture was extracted with CH2Cl2
(2 ꢃ 25 mL). The combined organic layer was washed with water
and brine and dried over anhydrous Na2SO4. Concentration of the
organic layer on a rotary evaporator gave a crude product which
was purified by column chromatography.
C
37H40O7 [M+Na]+ 619.2672; found [M+H]+ 619.2678.
4.6. (3aR,5R,6R,6aR)-6-(Benzyloxy)-5-((R)-1-(benzyloxy)-2-
(trityloxy)ethyl)-6-(2-benzyloxy)ethyl)-2,2-dimethyltetra-
hydrofuro[2,3-d][1,3]dioxole 17
Diol 16 (1.2 g, 2.0 mmol) was benzylated with NaH (0.192 g,
4.8 mmol) and benzyl bromide (0.57 mL, 4.8 mmol) using general
procedure (B) to give 17 (1.50 g, 96%) as a colorless thick liquid.
4.4. (R)-1-((3aR,5R,6R,6aR)-6-Allyl-6-(benzyloxy)-2,2-dimethyl-
tetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-2-(trityloxy)ethanol 15
Rf = 0.7 (hexane/EtOAc, 4:1). ½a D25
¼ þ3:8 (c 1.5, CH2Cl2). IR (neat)
ꢄ
m
max: 2985, 1077, 1027 cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.47–
.
Diol 14 (1 g, 2.85 mmol) was tritylated using general procedure
(A) to give 15 (1.522 g, 90%) as a colorless thick liquid. Rf = 0.5 (hex-
7.45 (m, 6H, ArH), 7.30–7.19 (m, 24H, ArH), 5.61 (d, 1H,
J = 3.1 Hz), 4.78–4.69 (m, 3H), 4.65 (d, 1H, J = 3.1 Hz), 4.51 (d, 1H,
J = 7.0 Hz), 4.46 (d, 1H, J = 11.4 Hz, –OCH2Ph), 4.34 (s, 2H, –OCH2Ph),
3.80 (br s, 1H), 3.65–3.58 (m, 2H), 3.42 (br s, 2H), 2.13–2.09
(m, 1H), 1.90–1.87 (m, 1H), 1.55 (s, 3H, –C(CH3)2), 1.30 (s, 3H,
–C(CH3)2) ppm. 13C NMR (125 MHz, CDCl3): d 144.0, 139.1, 138.5,
138.1, 128.7, 128.4, 128.3, 128.0, 127.9, 127.6, 127.5, 127.2,
127.1, 126.8, 112.2, 103.1, 86.5, 83.7, 83.3, 78.0, 72.9, 72.2, 67.0,
65.9, 63.6, 31.7, 26.7, 26.4 ppm. HRMS (ESI): calcd for C51H52O7
[M+H]+ 799.3611; found [M+H]+ 799.3618.
ane/EtOAc, 9:1). ½a D25
ꢄ
¼ þ5:9 (c 1.0, CH2Cl2). IR (neat)
mmax: 3524,
2983, 1089 cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.48–7.46 (m,
.
6H, ArH), 7.40–7.18 (m, 14H, ArH), 6.00–5.93 (m, 1H, –CH@CH2),
5.59 (d, 1H, J = 3.68 Hz), 5.18–5.12 (m, 2H, –CH@CH2), 4.74 (s,
2H, –OCH2Ph), 4.48 (d, 1H, J = 3.8 Hz), 4.31 (d, 1H, J = 9.2 Hz),
3.92 (br s, 1H), 3.34 (dd, 1H, J = 9.7, 2.4 Hz), 3.29 (dd, 1H, J = 9.7,
5.1 Hz), 2.70 (d, 1H, J = 3.6 Hz), 2.65 (dd, 1H, J = 14.6, 7.8 Hz), 2.55
(dd, 1H, J = 14.6, 6.6 Hz), 1.57 (s, 3H, –C(CH3)2), 1.33 (s, 3H, –C(CH3)2)
ppm. 13C NMR (100 MHz, CDCl3): d 144.0, 138.5, 132.5, 128.7,
128.2, 127.7, 127.3, 126.8, 118.7, 112.6, 103.8, 86.4, 84.5, 82.1,
78.5, 69.0, 67.4, 65.4, 35.8, 26.7, 26.6 ppm. HRMS (ESI): calcd for
4.7. (R)-2-(Benzyloxy)-2-((3aR,5R,6R,6aR)-6-(benzyloxy)-6-(2-
(benzyloxy)ethyl)-2,2 dimethyltetrahydrofuro-[2,3-d][1,3]dioxol-
5-yl)ethanol 18
C
38H40O6 [M+Na]+ 615.2723; found [M+Na]+ 615.2723.
4.5. (R)-1-((3aR,5R,6R,6aR)-6-(Benzyloxy)-6-(2-hydroxy-ethyl)-
2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-5-yl)-
2-(trityloxy)ethanol 16
To a stirred solution of compound 17 (1.50 g, 1.93 mmol) in
anhydrous methanol (10 mL) was added HClO4ꢀSiO2 (1.5 g) and
the reaction mixture was stirred at room temperature for 3 h.
The reaction mixture was then filtered, washed with methanol,
and then the combined organic extracts were concentrated under
vacuum. Purification through silica gel chromatography afforded
the pure alcohol 18 (0.950 g, 92%) as a colorless liquid. Rf = 0.5
At first, NMO (0.388 g, 3.29 mmol) and OsO4 (25 mg/mL solu-
tion in tBuOH, 0.05 mL, 0.005 mmol) were added to a stirred solu-
tion of compound 15 (1.5 g, 2.53 mmol) in acetone/water/tBuOH
(10 mL, 1:1:0.5) at room temperature. The reaction mixture was
stirred for 12 h and then treated with Na2S2O5 (0.623 g,
(hexane/EtOAc, 7:3). ½a D25
ꢄ
¼ þ40:2 (c 1.0 CH2Cl2). IR (neat) mmax
:
3440, 2933, 1590, 1166, 1026 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d
3.29 mmol). The reaction mixture was stirred for
a further
7.34–7.16 (m, 15H, ArH), 5.69 (d, 1H, J = 3.6 Hz), 4.78–4.70 (m,
3H), 4.64–4.56 (ABq, 2H, J = 11.4 Hz, –OCH2Ph), 4.46 (s, 3H,
–OCH2Ph), 3.84–3.76 (m, 3H), 3.74–3.65 (m, 2H), 2.46 (br s, 1H),
2.26–2.19 (m, 1H), 2.12–2.07 (m, 1H), 1.55 (s, 3H, –C(CH3)2), 1.33
(s, 3H, –C(CH3)2) ppm. 13C NMR (125 MHz, CDCl3): d 138.2, 137.9,
128.3, 128.2, 128.1, 127.6, 127.6, 127.5, 127.4, 127.3, 112.4,
103.4, 83.9, 82.6, 80.2, 73.0, 72.2, 67.2, 65.9, 61.8, 32.1, 26.7,
26.4 ppm. HRMS (ESI): calcd for C32H38O7 [M+Na]+ 557.2516;
[M+NH4]+ 557.2961 found [M+Na]+ 557.2518; [M+NH4]+ 557.2968.
30 min and then extracted with ethyl acetate (2 ꢃ 50 mL). The
combined organic extracts were washed with water and brine.
Evaporation of the organic layer followed by filtration through a
short column gave the diol which was taken in MeOH/H2O (9:1,
15 mL) and cooled to 0 °C. NaIO4 (1.082 g, 5.06 mmol) was added
to it and stirred the reaction mixture for 30 min at room tempera-
ture. The reaction was quenched by the addition of water and the
reaction mixture was concentrated under reduced pressure. The
residue obtained was extracted with ethyl acetate (2 ꢃ 50 mL)
and the combined organic layers were washed with brine and con-
centrated. The crude aldehyde was subjected to further reaction.
The aldehyde was dissolved in methanol and cooled to 0 °C. Next,
NaBH4 (1.082 g, 5.06 mmol) was added and the reaction mixture
was stirred for 2 h. The reaction was quenched by the addition of
a saturated NH4Cl solution and the reaction mixture was concen-
trated under high vacuum to remove the methanol. The aqueous
4.8. (R)-2-(Benzyloxy)-2-((3aR,5R,6R,6aR)-6-(benzyloxy)-6-
(2-(benzyloxy)ethyl)-2,2-dimethyltetrahydro-furo[2,3-d][1,3]
dioxol-5-yl)ethyl methanesulfonate 19
Alcohol 18 (0.900 g, 1.68 mmol) was converted into the mesy-
late following general procedure (C) to give compound 19

2970
P. Gupta et al. / Tetrahedron: Asymmetry 21 (2010) 2966–2972
(0.980 g, 95%) as a colorless liquid. Rf = 0.6 (hexane/EtOAc, 7:3).
¼ þ30:2 (c 1.0, CH2Cl2). IR (neat) max: 2934, 1496, 1357,
1175, 1027 cmꢁ1 1H NMR (400 MHz, CDCl3): d 7.34–7.17 (m,
73.3, 72.8, 66.0, 64.2, 50.6, 31.1 ppm. HRMS (ESI): calcd for
C
29H31N3O6[M+Na]+ 540.2111; found [M+Na]+ 540.2115.
½
a 2D5
ꢄ
m
.
15H, ArH), 5.66 (d, 1H, J = 3.4 Hz), 4.76–4.68 (m, 4H), 4.58 (dd,
1H, J = 11.2, 2.4 Hz), 4.53 (d, 1H, J = 11.2 Hz), 4.41 (s, 2H, –OCH2Ph),
4.38–4.32 (m, 2H), 3.93–3.90 (m, 1H), 3.72–3.68 (m, 1H), 3.67–3.61
(m, 1H), 2.91 (s, 3H, –SO2CH3), 2.16–2.11 (m, 1H), 1.98–1.93 (m,
1H), 1.57 (s, 3H, –C(CH3)2), 1.32 (s, 3H, –C(CH3)2) ppm. 13C NMR
(125 MHz, CDCl3): d 138.8, 138.0, 137.4, 128.5, 128.3, 128.2,
127.8, 127.5, 127.3, 112.7, 103.4, 83.8, 83.0, 77.9, 75.4, 73.2, 72.5,
69.7, 67.4, 65.7, 37.8, 32.0, 26.9, 26.5 ppm. HRMS (ESI): calcd for
4.11. (2R,3R,4R)-5-Azido-2,4-bis(benzyloxy)-2-(2-(benzyloxy)ethyl)
pentane-1,3-diol 22
At first, sodium borohydride (0.015 g, 0.39 mmol) was added to
a stirred solution of aldehyde 21 (0.400 g, 0.77 mmol) in methanol
(5 mL) and cooled to 0 °C. The reaction mixture was stirred over-
night and then quenched by the addition of saturated NH4Cl solu-
tion (2 mL). The reaction mixture was concentrated under high
vacuum to remove methanol. The aqueous phase was extracted
with ethyl acetate (20 ꢃ 2 mL) and the combined organic extracts
were washed with water and brine and dried with anhydrous
Na2SO4. Purification through column chromatography furnished
the diol 22 (0.316 g, 83%) as a colorless liquid. Rf = 0.6 (hexane/
C
33H40O9S [M+Na]+ 635.2291; found [M+Na]+ 635.2293.
4.9. (3aR,5R,6R,6aR)-5-((R)-2-Azido-1-(benzyloxy)ethyl)-6-
(benzyloxy)-6-(2-(benzyloxy)ethyl)-2,2-dimethyltetrahydrofuro
[2,3-d][1,3]dioxole 20
EtOAc, 7:3). ½a 2D5
ꢄ
¼ þ20:0 (c 0.1, CH2Cl2). IR (neat)
mmax: 3433,
2918, 2100, 1591, 1065, 1027 cmꢁ1
.
1H NMR (500 MHz, CDCl3): d
To a stirred solution of mesylate 19 (0.900 g, 1.46 mmol) in dry
DMF (10 mL) was added NaN3 (6 mmol). This heterogeneous mix-
ture was stirred at 120 °C for 3 h, cooled to room temperature,
water (10 mL) was added, and extracted with diethyl ether
(3 ꢃ 10 mL). The combined organic layer was washed with brine
solution and dried over Na2SO4. Solvent removal under reduced
pressure gave a residue, which upon purification through column
chromatography gave azide 20 (0.700 g, 85%) as a viscous liquid.
7.38–7.25 (m, 15H, ArH), 4.68 (d, 1H, J = 11.0 Hz, –OCH2Ph), 4.61–
4.56 (ABq, 2H, J = 11.0 Hz, –OCH2Ph), 4.53 (d, 1H, J = 11.0 Hz,
–OCH2Ph), 4.51 (s, 2H, –OCH2Ph), 3.94 (s, 2H), 3.76–3.59 (m, 5H),
3.55 (dd, 1H, J = 13.3, 2.7 Hz), 3.18 (br s, 1H), 3.13 (s, 1H), 2.38–
2.29 (m, 1H), 2.19–2.05 (m, 1H) ppm. 13C NMR (125 MHz, CDCl3):
d 138.5, 137.3, 137.2, 128.4, 128.1, 127.9, 127.8, 127.5, 127.3, 80.4,
78.1, 73.4, 72.5, 71.9, 65.6, 64.8, 64.6, 50.9, 30.7 ppm. HRMS (ESI):
calcd for C28H33N3O5[M+H]+ 492.2498; found [M+H]+ 492.2495.
Rf = 0.7 (hexane/EtOAc, 4:1). ½a D25
ꢄ
¼ þ34:4 (c 1.8, CH2Cl2). IR (neat)
m
max: 2933, 2101, 1166, 1026 cmꢁ1 1H NMR (400 MHz, CDCl3): d
.
7.34–7.16 (m, 15H, ArH), 5.65 (d, 1H, J = 3.6 Hz), 4.77–4.66 (m,
4H), 4.55 (d, 1H, J = 11.0 Hz), 4.39 (s, 3H), 3.80 (td, 1H, J = 6.6,
2.9 Hz), 3.71–3.56 (m, 3H), 3.49 (dd, 1H, J = 13.4, 6.0 Hz), 2.18–
2.11 (m, 1H), 1.98–1.92 (m, 1H), 1.58 (s, 3H, –C(CH3)2), 1.32 (s,
3H, –C(CH3)2) ppm. 13C NMR (125 MHz, CDCl3): d 137.1, 136.2,
135.7, 126.6, 126.4, 126.3, 126.1, 125.9, 125.8, 125.6, 125.3,
110.8, 101.4, 81.9, 81.3, 77.0, 74.8, 71.3, 70.7, 65.4, 63.9, 50.1,
30.2, 25.0, 24.7 ppm. HRMS (ESI): calcd for C32H37N3O6 [M+Na]+
582.2580; found [M+H]+ 582.2581.
4.12. (2R,3R,4R)-1-Azido-2,4,6-tris(benzyloxy)-4-(trityloxymethyl)
hexan-3-diol 23
Following the general procedure (A) for the tritylation gave the
compound 23 (0.345 g, 77%) as a colorless liquid. Rf = 0.5 (hexane/
EtOAc, 9:1). ½a 2D5
ꢄ
¼ þ9:0 (c 0.7, CH2Cl2). IR (neat)
mmax: 3428, 2923,
2100, 1595, 1450, 1056, 1028 cmꢁ1.1H NMR (500 MHz, CDCl3): d
7.44–7.38 (m, 10H, ArH), 7.34–7.25 (m, 16H, ArH), 7.20–7.19 (m,
2H, ArH), 7.05–7.03 (m, 2H, ArH), 4.82–4.77 (ABq, 2H, J = 11.4 Hz,
–OCH2Ph), 4.44 (d, 1H, J = 10.5 Hz, –OCH2Ph), 4.35–4.29 (ABq, 2H,
J = 11.9 Hz, –OCH2Ph), 4.10 (d, 1H, J = 10.5 Hz, –OCH2Ph), 3.79–
3.77 (m, 1H,), 3.72–3.69 (m, 1H), 3.60 (dd, 1H, J = 13.3, 2.7 Hz),
3.57–3.49 (m, 3H), 3.47 (d, 1H, J = 10.5 Hz), 3.39–3.36 (m, 1H),
3.27 (d, 1H, J = 10.5 Hz), 2.46–2.41 (m, 1H), 2.39–2.34 (m, 1H)
ppm. 13C NMR (125 MHz, CDCl3): d 143.6, 139.4, 137.9, 137.6,
128.9, 128.6, 128.5, 128.4, 128.1, 127.9, 127.8, 127.7, 127.4,
127.3, 127.2, 87.1, 81.0, 78.8, 73.8, 73.3, 72.0, 66.5, 66.2, 65.1,
4.10. (2R,3R,4R)-1-Azido-2,4,6-tris(benzyloxy)-4-formylhexan-
3-yl formate 21
A solution of azide 20 (0.500 g, 0.89 mmol) in TFA–water (2 mL,
1:1) was stirred for 1 h at room temperature. The reaction mixture
was then cooled to 0 °C, diluted with CH2Cl2 (5 mL), and quenched
by the careful addition of saturated K2CO3 solution. This mixture
was partitioned and the aqueous phase was extracted with CH2Cl2
(20 ꢃ 2 mL). The combined organic extracts were washed with
water and brine, dried with anhydrous Na2SO4, and the solvents
were removed. The crude product was dissolved in MeOH/H2O
(9:1, 5 mL) and cooled to 0 °C. Next, NaIO4 (0.285 g, 1.34 mmol)
was added and stirred for 8 h at room temperature. Water was
added to the reaction mixture and the solvent was evaporated in
vacuo. The residue was extracted with ethyl acetate (20 ꢃ 2 mL)
and the combined organic layers were washed with brine and con-
centrated. Purification through column chromatography furnished
the pure compound 21 (0.406 g, 88%) as a colorless liquid. Rf = 0.7
51.6, 30.8 ppm. HRMS (ESI): calcd for
C
47H47N3O5 [M+Na]+
756.3414; found [M+Na]+ 756.3414.
4.13. (2R,3R,4R)-1-Azido-2,3,4,6-tetra(benzyloxy)-4-
(trityloxymethyl)hexane 24
Following general procedure for benzylation (B) gave the com-
pound 24 (0.325 g, 96.7%) as a colorless liquid. Rf = 0.6 (hexane/
EtOAc, 9:1). ½a 2D5
ꢄ
¼ þ16:3 (c 1.0, CH2Cl2). IR (neat)
mmax: 2920,
2099, 1592, 1451, 1088, 1028 cmꢁ1
.
1H NMR (500 MHz, CDCl3): d
(hexane/EtOAc, 7:3). ½a D25
ꢄ
¼ þ13:0 (c 0.4, CH2Cl2). IR (neat) mmax
:
7.44–7.42 (m, 6H, ArH), 7.35–7.23 (m, 29H, ArH), 4.88 (d, 1H,
J = 11.4 Hz, –OCH2Ph), 4.66–4.57 (m, 3H, –OCH2Ph), 4.50–4.45
(ABq, 2H, J = 11.5 Hz, –OCH2Ph), 4.36 (s, 2H, –OCH2Ph), 4.10 (d,
1H, J = 2.7 Hz), 3.94–3.93 (m, 1H,), 3.56–3.52 (m, 2H), 3.49–3.40
(m, 3H), 3.19 (d, 1H, J = 10.1 Hz), 2.50–2.44 (m, 1H), 2.36–2.30
(m, 1H) ppm. 13C NMR (125 MHz, CDCl3): d 143.5, 139.2, 138.5,
138.4, 138.1, 129.0, 128.6, 128.5, 128.4, 128.1, 128.0, 127.9,
127.8, 127.7, 127.5, 127.3, 127.2, 87.0, 82.5, 80.5, 80.1, 75.0, 73.1,
72.4, 66.1, 65.6, 64.8, 52.3, 31.1 ppm. HRMS (ESI): calcd for
2923, 2105, 1736, 1595, 1364, 1129, 1025 cmꢁ1
.
1H NMR
(400 MHz, CDCl3): d 9.38 (s, 1H, –CHO), 8.17 (s, 1H, –OCHO),
7.41–7.18 (m, 15H, ArH), 5.59 (d, 1H, J = 8.7 Hz), 4.77–4.71 (ABq,
2H, J = 11.7 Hz, –OCH2Ph), 4.59–4.51 (ABq, 2H, J = 11.0 Hz,
–OCH2Ph), 4.44–4.36 (ABq, 2H, J = 11.9 Hz, –OCH2Ph), 3.81–3.76
(m, 1H), 3.56–3.50 (m, 2H), 3.41 (dd, 1H, J = 13.4, 3.1 Hz), 3.14
(dd, 1H, J = 13.4, 4.6 Hz), 2.27–2.11 (m, 2H) ppm. 13C NMR
(125 MHz, CDCl3): d 199.5, 159.2, 137.6, 137.5, 136.6, 128.6,
128.5, 128.4, 128.1, 128.0, 127.8, 127.7, 127.1, 83.8, 76.4, 76.2,
C
54H53N3O5 [M+Na]+ 846.3883; found [M+Na]+ 846.3888.

P. Gupta et al. / Tetrahedron: Asymmetry 21 (2010) 2966–2972
2971
4.14. (2R,3R,4R)-5-Azido-2,3,4-tris(benzyloxy)-2-(2-(benzyloxy)
ethyl)pentan-1-diol 25
127.8, 127.6, 127.4, 81.7, 79.2, 79.1, 78.3, 75.2, 73.3, 71.9, 70.1,
65.2, 41.2, 36.9, 31.1, 28.4 ppm. HRMS (ESI): calcd for C41H51NO9S
[M+H]+ 734.3363; found [M+H]+ 734.3366.
Trifluoroacetic acid (0.05 mL, 0.72 mmol) was added dropwise
to a solution of compound 24 (0.300 g, 0.36 mmol) cooled to 0 °C,
then stirred at the same temperature for 30 min, diluted with
CH2Cl2 (5 mL), and quenched by the careful addition of saturated
K2CO3 solution. This mixture was partitioned and the aqueous
phase was extracted with CH2Cl2 (20 ꢃ 2 mL). The combined or-
ganic extracts were washed with water and brine, dried with anhy-
drous Na2SO4, and concentrated under reduced pressure.
Purification through column chromatography gave alcohol 25
(0.170 g, 80.5%) as a colorless liquid. Rf = 0.6 (hexane/EtOAc, 4:1).
4.17. (3S,4R,5R)-tert-Butyl 3,4,5-tris(benzyloxy)-3-(2-(benzyloxy)
ethyl)piperidine-1-carboxylate 28
At first, NaH (60% suspension in mineral oil, 0.014 g, 0.34 mmol)
was added portionwise to a stirred solution of the mesylate 27
(0.125 g, 0.17 mmol) in THF (5 mL) at 0 °C. The reaction mixture
was refluxed for 4 h. Excess NaH was quenched by pouring the
reaction mixture into ice and then extracted with ethyl acetate
(2 ꢃ 15 mL) followed by washing with water and brine solution.
The organic layer was dried with anhydrous Na2SO4, and concen-
trated in vacuo. Purification through column chromatography gave
piperidine 28 (0.081 g, 75%) as a colorless liquid. Rf = 0.6 (hexane/
½
a 2D5
ꢄ
¼ þ12:2 (c 0.5, CH2Cl2). IR (neat)
mmax: 3442, 2923, 2868,
2099, 1453, 1092, 1066, 1027 cmꢁ1 1H NMR (400 MHz, CDCl3): d
.
7.37–7.21 (m, 20H, ArH), 4.84 (d, 1H, J = 11.2 Hz, –OCH2Ph), 4.65–
4.53 (m, 5H, –OCH2Ph), 4.47–4.40 (ABq, 2H, J = 11.7 Hz, –OCH2Ph),
4.02–3.99 (m, 1H), 3.94 (d, 1H, J = 2.7 Hz), 3.69–3.68 (br s, 2H),
3.60–3.53 (m, 3H), 3.52–3.47 (m, 1H), 3.19 (br s, 1H), 2.19–2.17
(m, 1H), 2.11–2.08 (m, 1H) ppm. 13C NMR (100 MHz, CDCl3): d
138.9, 138.2, 137.9, 137.6, 128.7, 128.6, 128.5, 128.1, 128.0,
127.9, 127.5, 127.3, 82.2, 80.6, 79.9, 75.2, 73.5, 72.4, 65.8, 65.3,
64.8, 52.3, 30.9 ppm. HRMS (ESI): calcd for C35H39N3O5 [M+H]+
582.2968; found [M+H]+ 582.2966.
EtOAc, 4:1). ½a 2D5
ꢄ
¼ ꢁ5:0 (c 0.4, CH2Cl2). IR (neat)
mmax: 2926,
1693, 1495, 1454, 1391, 1050, 1027 cmꢁ1
.
1H NMR (500 MHz,
CDCl3, rotamer ratio approximately 1:1): d 7.42–7.32 (m, 40H,
ArH), 5.03 (br s, 1H, –OCH2Ph), 4.90 (br s, 1H, –OCH2Ph), 4.85 (br
s, 1H, –OCH2Ph), 4.76 (br s, 1H, –OCH2Ph), 4.65 (br s, 1H, –OCH2Ph),
4.55–4.49 (m, 10H, –OCH2Ph), 4.46 (br s, 1H, –OCH2Ph), 4.13 (br s,
1H), 4.07 (br s, 1H), 3.99 (br s, 1H), 3.88 (br s, 1H), 3.77 (br s, 4H),
3.72 (br s, 4H), 3.39 (br s, 2H), 3.28 (br s, 2H), 2.08–2.04 (m, 4H),
1.50 (s, 18H, –C(CH3)3) ppm. 13C NMR (125 MHz, CDCl3, rotamer
ratio approximately 1:1): d 155.1, 154.9, 139.6, 139.4, 139.0,
138.7, 138.5, 138.2, 128.6, 128.5, 128.4, 128.2, 128.1, 128.0,
127.8, 127.6, 127.4, 127.3, 80.1, 78.8, 78.5, 78.1, 75.0, 74.9, 74.6,
74.4, 73.5, 71.3, 70.9, 65.6, 63.9, 46.5, 45.8, 43.1, 41.8, 31.2,
28.5 ppm. HRMS (ESI): calcd for C40H47NO6 [M+H]+ 638.3481;
found [M+H]+ 638.3482.
4.15. (2R,3R,4R)-5-Azido-2,3,4-tris(benzyloxy)-2-(2-(benzyloxy)
ethyl)pentyl methanesulfonate 26
Alcohol 25 (0.150 g, 0.25 mmol) was mesylated following gen-
eral procedure (C) to give compound 26 (0.165 g, 97%) as a color-
less liquid. Rf = 0.5 (hexane/EtOAc, 4:1).
½
a 2D5
ꢄ
¼ þ11:2 (c 0.9,
CH2Cl2). IR (neat)
m
max: 2918, 2100, 1360, 1177, 1097, 1027 cmꢁ1
.
1H NMR (500 MHz, CDCl3): d 7.35–7.26 (m, 20H, ArH), 4.81 (d,
1H, J = 11.4 Hz, –OCH2Ph), 4.67–4.60 (m, 4H, –OCH2Ph), 4.56 (d,
1H, J = 11.0 Hz, –OCH2Ph), 4.44 (br s, 2H, –OCH2Ph), 4.42–4.36
(ABq, 2H, J = 11.0 Hz, –OCH2Ph), 4.01 (m, 1H), 3.96 (d, 1H,
J = 4.1 Hz), 3.67–3.59 (m, 2H), 3.55 (dd, 1H, J = 13.7, 2.7 Hz), 3.51
(dd, 1H, J = 13.3, 6.4 Hz), 2.71 (s, 3H, –SO2CH3), 2.33–2.27 (m,
1H), 2.21–2.15 (m, 1H) ppm. 13C NMR (125 MHz, CDCl3): d 138.2,
138.0, 137.9, 137.5, 128.6, 128.5, 128.3, 128.1, 128.0, 127.9,
127.7, 127.4, 81.1, 79.4, 79.3, 75.3, 73.3, 72.6, 70.1, 65.7, 65.3,
51.9, 36.9, 30.6 ppm. HRMS (ESI): calcd for C36H41N3O7S [M+H]+
660.2743; found [M+H]+ 660.2742.
4.18. (3S,4R,5R)-3-(2-Hydroxyethyl)piperidine-3,4,5-triol 10
A solution of 28 (0.075 g, 0.12 mmol) in methanol (10 mL) was
stirred under H2 (20 psi) in the presence of 20% Pd(OH)2/C (25 mg)
for 12 h. After completion of the reaction, the reaction mixture was
filtered through a pad of Celite and the filtrate was concentrated.
The residue was dissolved in methanol (1.5 mL), after which was
added 6 M aqueous HCl (1.5 mL) and stirred at room temperature
for 12 h. The reaction mixture was passed through a Dowex
(50X) basic resin column and concentrated under reduced pressure
to give piperidine 10 (0.020 g, quantitative yield). Rf = 0.3 (EtOAc/
MeOH, 7:3). ½a 2D5
ꢄ
¼ ꢁ12:5 (c 0.5, MeOH). 1H NMR (500 MHz,
CDCl3): d 3.87 (br s, 1H, H-5), 3.61 (t, 2H, J = 6.9 Hz, H-8, H-80),
3.53 (d, 1H, J = 2.3 Hz, H-4), 2.95 (d, 1H, J = 13.7 Hz, H-6), 2.87 (d,
1H, J = 13.7 Hz, H-2), 2.77 (d, 1H, J = 13.7 Hz, H-60), 2.66 (d, 1H,
J = 13.7 Hz, H-20), 1.81–1.76 (m, 1H, H-7), 1.71–1.65 (m, 1H, H-70)
ppm. 13C NMR (125 MHz, CDCl3): d 72.9, 70.4, 67.9, 56.5, 51.0,
47.6, 37.5 ppm. HRMS (ESI): calcd for C7H15NO4 [M+H]+
178.1079; found [M+H]+ 178.1079.
4.16. (2R,3R,4R)-2,3,4-Tris(benzyloxy)-2-(2-(benzyloxy)ethyl)-5-
(tert-butoxycarbonyl-amino)pentyl methanesulfonate 27
To a stirred solution of azide 26 (0.150 g, 0.22 mmol) in THF/
H2O (9:1, 2 mL) was added Ph3P (0.078 g, 0.3 mmol). The reaction
mixture was stirred for 8 h at room temperature. Concentration
under reduced pressure afforded the crude amine, which was ta-
ken in ethyl acetate (3 mL) and cooled to 0 °C. Next, saturated NaH-
CO3 solution (2 mL) was added followed by Boc2O (0.1 mL,
0.44 mmol). The reaction mixture was stirred overnight, after
which it was extracted with ethyl acetate, washed with water
and brine, and dried over Na2SO4. Solvent evaporation followed
by purification through column chromatography gave the Boc pro-
tected amine 27 (0.134 g, 80.7%) as a colorless liquid. Rf = 0.4 (hex-
Acknowledgments
We thank the Council of Scientific and Industrial Research, New
Delhi for the financial support [Grant No. 01(2298)/09/EMR-II]. We
also thank the U.G.C., New Delhi for fellowship to P.G. and CSIR,
New Delhi for fellowship to S.D.
ane/EtOAc, 4:1). ½a D25
ꢄ
¼ þ16:8 (c 0.4, CH2Cl2). IR (neat)
mmax: 3434,
2931, 1710, 1363, 1176, 1027 cmꢁ1
.
1H NMR (400 MHz, CDCl3): d
References
7.33–7.24 (m, 20H, ArH), 4.84–4.81 (m, 2H, –OCH2Ph, –NHBoc),
4.66–4.58 (m, 3H), 4.55 (d, 1H, J = 11.4 Hz, –OCH2Ph), 4.48–4.41
(m, 5H), 3.97 (d, 1H, J = 2.7 Hz), 3.89 (m, 1H), 3.67 (m, 2H), 3.54
(m, 1H), 3.37 (m, 1H), 2.72 (s, 3H, –SO2CH3), 2.30–2.23 (m, 2H),
1.39 (s, 9H, –C(CH3)3) ppm. 13C NMR (100 MHz, CDCl3): d 156.0,
138.3, 138.1, 138.0, 128.5, 128.4, 128.3, 128.3, 128.1, 128.0,
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a-galactosidase (coffee beans), b-galactosidase (Aspergillus
a