Azidation of anomeric nitro sugars: application in the synthesis of spiroaminals as glycosidase inhibitors

Article abstract of DOI:10.1016/j.tetlet.2010.03.003

6,5-Fused sugar-derived spiroaminals have been synthesized from the azido esters obtained via the nucleophilic substitution reactions of unstable Michael adducts derived from 1-nitro sugars. Most of the spiroaminals synthesized showed moderate but selecti

Full text of DOI:10.1016/j.tetlet.2010.03.003

Tetrahedron Letters 51 (2010) 2519–2524
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Azidation of anomeric nitro sugars: application in the synthesis
of spiroaminals as glycosidase inhibitors
*
A. P. John Pal, 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:
6,5-Fused sugar-derived spiroaminals have been synthesized from the azido esters obtained via the
nucleophilic substitution reactions of unstable Michael adducts derived from 1-nitro sugars. Most of
the spiroaminals synthesized showed moderate but selective inhibitory activities toward some
glycosidases.
Received 24 December 2009
Revised 24 February 2010
Accepted 1 March 2010
Available online 3 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Nitro sugars
Hydrolysis
Azidation
Spiroaminals
Glycosidase inhibitors
Nitro compounds are versatile intermediates in organic synthe-
sis due to their easy availability and transformation into a wide
variety of functionalities.1 Carbohydrate chemists have long recog-
nized nitro sugars as both novel compounds and synthetically use-
ful intermediates.2 Both saturated and unsaturated nitro groups
have been used in the synthesis of a number of useful compounds.3
In 1-nitro sugars, having a nitro group at the anomeric carbon,
the strong electron-withdrawing property of the nitro group can
facilitate an easy removal of the anomeric proton under mild basic
conditions. The stabilized glycosyl anions can easily react with dif-
ferent electrophiles like Michael acceptors and carbonyl com-
pounds leading to the generation of useful C-glycosyl adducts. By
utilizing these properties of 1-nitro sugars, Vasella and co-workers
synthesized several molecules such as N-acetylneuraminic acid
and their analogues,4 sialidase inhibitors, 6-amino-6-deoxysialic
acids,5 and various biologically important carbohydrates such as
methyl shikimate and diethyl phosphashikimate.6
ylated-1-nitro furanoses (a-nitro ether link) with hydroxy group
under solvolytic condition and also with 2,4-bis(trimethylsilyl-
oxy)-pyrimidine in the presence of FeCl3 in CH3CN at higher tem-
peratures for the synthesis10 of ketose-derived nucleosides.
Because of diverse applications and also due to our continued
interest11 in exploring the chemistry of nitro sugars we hereby re-
port on the functionalization of 1-nitro sugars and its application
in the synthesis of some spiro-compounds which are moderate gly-
cosidase inhibitors. Toward this purpose, we have utilized the
chemistry of 1-nitro sugars 1 and 4 (Table 1)12 derived from
cose and -mannose, respectively.
D-glu-
D
Reaction of nitro sugar 1 with methyl acrylate in the presence of
a catalytic amount of n-tetrabutylammonium fluoride (TBAF), at
0 °C presumably gave the adduct 2a (Table 1), as was observed
by its IR spectrum immediately after work-up (with an intense
peak at 1554 cmꢀ1 indicating the presence of a nitro group), whose
purification by column chromatography led only to the formation
of the hydroxyl derivative 3a in 83% yield. Further, it was observed
that the adduct 2a was not only unstable on silica gel but it slowly
got converted into 3a by merely keeping it at room temperature
(Table 1). The 1H NMR spectrum of 3a showed a characteristic peak
of -OMe as a singlet at d 3.66 and the methylene protons as multi-
plets at d 2.63–1.74. The Michael addition with acrylonitrile also
gave the hydroxyl compound viz. hydroxy nitrile 3b whose struc-
ture was easily established from its spectral analysis and NOE data.
The treatment of 1 with ethyl propiolate in CH2Cl2 with Et3N at
ꢀ30 °C gave the unsaturated trans ester 3c in 51% yield along with
a complex mixture of products. The 1H NMR spectrum of 3c
showed the presence of two olefinic protons at d 6.83 and d 6.19
It is well known in the literature7 that in an aliphatic compound
a nitro group can be easily replaced by various nucleophiles via
SRN1 or ionic processes. In some cases, it has also been observed
that the nitro group of C-glycosylated-1-nitro sugars can be easily
replaced by a hydroxy group during solvolysis. Thus, Vasella8 re-
placed nitro group present in C-glycosylated-1-nitropyranoses
and furanoses with sodium salt of nitromethane (Kornblum reac-
tion) for the synthesis of branched sugars. Further, Vasella and
co-workers9 have also reported SN1-type substitution of C-glycos-
* Corresponding author. Tel.: +91 512 2597169; fax: +91 512 259 0007.
E-mail address: vankar@iitk.ac.in (Y.D. Vankar).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.03.003

2520
A. P. John Pal, Y. D. Vankar / Tetrahedron Letters 51 (2010) 2519–2524
Table 1
Michael additions using nitro sugars 1 and 4
BnO
BnO
R2
O
R2
O
BnO
BnO
R2
BnO
Electrophile
Column
O
BnO
R
R
BnO
BnO
BnO
Chromatography
R1
R1
TBAF, 0 °C
30 min
R1
NO2
NO2
OH
R1 = OBn, R2 = H
R1 = H, R2 = OBn
2a,2b, 2f
4a
1
4
R1 = OBn, R2 = H
R1 = H, R2 = OBn
R1 = OBn, R2 = H
R1 = H, R2 = OBn
3a-3c
4e
Entry
1
Nitro sugar
Electrophiles
Michael adducts
Hydrolyzed products
BnO
BnO
BnO
O
O
OMe
O
O
BnO
BnO
1
BnO
OMe
OMe
83%
O
BnO
BnO
NO2
NO2
NO2
NO2
OH
3a,
2a
BnO
BnO
BnO
BnO
O
O
CN
CN
3b,
2
1
CN
BnO
BnO
BnO
BnO
OH
2b
58%
BnO
BnO
BnO
BnO
O
O
O
O
O
3
4
1
4
BnO
BnO
OEt
2f
OEt
BnO
BnO
OEt
OH
3c, 51%
BnO
BnO
BnO
OBn
OBn
O
O
O
OMe
O
BnO
BnO
BnO
OMe
OMe
O
OH
4e
4a
, 78%
with J = 15.6 Hz confirming that the geometry of the double bond is
trans. Reaction of mannosyl nitro sugar 4 with methyl acrylate also
gave the ketose 4e (Table 1) in 78% yield. Although its structure
was confirmed by spectral means,13a the stereochemistry at the
anomeric center could not be established. In contrast with these
Michael adducts, the aldol products13b 1a, 1b, 2d, and 4d (Scheme
1) were found to be more stable at room temperature and also on
silica gel during column chromatography. These results clearly
suggest that a nitro group at the anomeric carbon having certain
substituents, as discussed above, is a rather labile leaving group.
We, therefore, explored the efficiency of the anomeric nitro group
as a leaving group in reactions with azide as a nucleophile in C-gly-
cosylated-1-nitro sugars.
Our initial attempts for the azidation of the crude Michael ad-
ducts 2a–d with sodium azide in DMF at higher temperatures led
to the formation of a mixture of two products, the hydrolyzed
products and the desired glycosyl azides in almost 1:1 ratio.
Next, we investigated the azidation of the Michael adducts by
Lewis acid activation. Gratifyingly, the formation of the undesired
hydrolysis products was completely suppressed under Lewis acid
conditions and glycosyl azides were formed as single isomers.
Thus, the treatment of the Michael adduct 2a in CH2Cl2 with
TMSN3 in the presence of TMSOTf and 4 Å powdered molecular
sieves at 0 °C produced the desired glycosyl azide 5a (Table 2) in
91% yield. Use of BF3.OEt2 at ꢀ40 °C and ꢀ78 °C also produced
the desired product, but the yields were poor. Best results were ob-
tained by using 50 mol % of TMSOTf in CH2Cl2 at 0 °C to room tem-
perature. Reduction in catalyst loading was ineffective as it led to
longer reaction time and reduction in chemical yield due to the for-
mation of undesired products.
Using these optimized reaction conditions we prepared the gly-
cosyl azides 5b, 5c, and 5e from the corresponding Michael adducts
in good to moderate yields. But in the case of nitro acetate 2d, one
mole equivalent of the catalyst was needed to get the azido acetate
5d. The stereochemistry of the newly generated anomeric center
was determined by 1H NMR spectroscopic analysis, COSY, and
NOE experiments.
Utilization of the optimized conditions, vide supra, for the con-
version of nitro sugars 4a–c, derived from D-mannose, led to the
desired azides 6a–c as single isomers in 72%, 80%, and 78% yields,
BnO
BnO
O
BnO
BnO
HCHO, MeOH
Ac2O, Et3N
O
BnO
1a
BnO
BnO
1
4
OAc
NO2
OH
NO2
BnO
K2CO3, 0-10 °C
56%
CH2Cl2, 0 °C - RT
80%
2d
, major isomer
BnO
BnO
OBn
O
OAc
NO2
4d, major isomer
OBn
Ac2O, Et3N
HCHO, DMF
BnO
O
BnO
BnO
BnO
CH2Cl2, 0 °C - RT
62%
OH
NO2
K2CO3, 0-10 °C
1b
Scheme 1. Henry reactions of nitro sugars 1 and 4 with formaldehyde.

A. P. John Pal, Y. D. Vankar / Tetrahedron Letters 51 (2010) 2519–2524
2521
Table 2
Azidation of Michael adducts in the presence of TMSN3 and TMSOTf at lower temperatures (0 °C to rt)
OBn
OBn
TMSN3 (1.5 eq)
O
BnO
BnO
O
BnO
BnO
R
R
BnO
TMSOTf (0.5 eq), CH2Cl2
4-Å MS, 0 °C-RT, 30 min.
BnO
NO2
N3
5a-5e, 6a-6d
2a-2e, 4a-4d
Entry
1
Michael adducts
Tertiary anomeric azides
Yield (%)
OBn
O
O
BnO
BnO
2a
90
85
79
OMe
5a
BnO
N3
OBn
O
BnO
BnO
CN
2
3
2b
BnO
N3
5b
OBn
OBn
O
O
O
O
BnO
BnO
BnO
BnO
OEt
OEt
BnO
BnO
NO2
N3
5c
2c
OBn
O
BnO
BnO
4
5
6
7
2d
86
83
72
80
OAc
BnO
N3
5d
OBn
OBn
O
O
O
O
BnO
BnO
BnO
BnO
BnO
NO2
BnO
5e
N3
2e
OBn
O
OBn
O
BnO
BnO
4a
OMe
6a
N3
OBn
OBn
OBn
OBn
O
O
BnO
BnO
BnO
CN
O
CN
BnO
6b
NO2
N3
4b
OBn
OBn
O
OBn
O
OBn
O
BnO
BnO
BnO
BnO
8
9
78
80
OEt
OEt
6c
4c
N3
NO2
OBn
OBn
O
BnO
BnO
4d
OAc
N3
6d
respectively. Further, similar to nitro acetate 2d, the mannose-de-
rived nitro acetate 4d was also found to be less reactive. The reac-
tion of this acetate with TMSN3 also required 1.0 equiv of TMSOTf
to afford the desired azido acetate 6d in 80% yield. Compound 6d
was a single isomer as it showed the presence of only one -OCOCH3
group in its 1H NMR spectrum at d 2.02 as a singlet suggesting that
only one anomer was present. Unfortunately, the stereochemistry
at the anomeric center could not be confirmed by NOE experi-
ments. However, based on literature analogy,14 we presume that
the azide group in this molecule is axially oriented.
experiments for ketose 3a (Fig. 1) irradiation of H-3 proton at d
3.34 enhanced the signal for H-30 methylene proton at d 1.75
(3.4% NOE), whereas irradiation of H-4 at d 4.02 and H-6 at d
3.97 protons did not show any enhancement in H-30 methylene
protons signal. These results indicated that the hydroxy group
has occupied axial position. In a similar manner, the stereochemis-
try of ketoses 3b and 3c was also established. Irradiation of H-3
proton at d 3.45 in compound 5a showed enhancement of H-30
methylene protons signal at d 2.26 and d 2.1 (2.0% and 3.0% NOE,
respectively, Fig. 1). In contrast, irradiation of H-4 proton signal
at d 3.99 did not show any enhancement of H-30 methylene protons
signal, clearly indicating that azide occupies the axial position.
The stereochemistry at the anomeric center of ketoses and ano-
meric azides was confirmed by NOE experiments. Thus, in NOE

2522
A. P. John Pal, Y. D. Vankar / Tetrahedron Letters 51 (2010) 2519–2524
(0.7% only). These results clearly establish the axial orientation of
the azide group in compound 6a. In a similar manner, the stereo-
chemistry of azides 6b and 6c was also established.
4.0%
3.4%
OBn
6H
OBn
H
H
BnO 5
BnO
6H
O1
BnO 5
O1
Y
X
For the past few years, we have been interested in developing
BnO4
3
3'
B3nO
2
OH
2
OH
4
BnO
synthesis of novel carbohydrate entities such as hybrids of
ose with 1-deoxynojirimycin analogues,11c sugar-carbamino sugar
hybrids,16a hybrids of nojirimycin d-lactam -galactose11d, and pyr-
rolidine-based imino sugars,16b natural products
-(+)-swainso-
D-galact-
H
H
3c Y = CO2Et
3a
D
2.0%
OBn
OBn
L
OBn
X
6 H3.0%
O
nine16c, and (+)-lentiginosine.16d In connection with our program
of developing novel carbohydrate molecules as glycosidase inhibi-
tors, we became interested in making sugar-derived spiroaminals
as glycosidase inhibitors. Spiroaminals, also called as oxa-aza spiro-
bicyclic frameworks, are the substructures present in a number of
biologically active compounds viz. pandamarilactone,17a hydantoci-
din, azaspiracid-1,17b immunosuppressant sanglifehrin,17c and a
spironucleoside as a potent glycosidase inhibitor.17d Because of the
unique structural features and potent herbicidal properties of the
natural product hydantocidin 7, several reports18 have appeared
5
1
6
5
BnO
BnO
O1
H
H
H
BnO
3
H
H3'
3'
3 H
0.7%
X
4
H
BnO
4
H
2
BnO
N3
N3
6a
X = CO2Me 5a
Figure 1. NOE correlations of compounds 3a, 3c, 5a, and 6a.
for its synthesis and also a wide range of analogues. The D-glucopyr-
OH
HO
OH
anose analogue of hydantocidin19a,b viz. compound 8 (Fig. 2) is a
powerful inhibitor of glycogen phosphorylase (GP). Keeping these
activities in mind we planned to synthesize sugar-derived
spiroaminals.19c
HO
H
N
OH
OH
H
O
N
O
O
O
HN
OH
HN
O
O
To convert 1-C-alkyl-1-azido sugars into spirolactams, we stud-
ied their reductions under different conditions. There are only few
reports in the literature regarding the reduction of C-glycosylated-
1-azido sugars.20a–d Our initial attempts for the reduction of azide
5a with PPh3 along with H2O21 and Zn-AcOH20a conditions were
unsuccessful. Treatment of ester 5a with Zn-AcOH at room temper-
ature gave a complex mixture, which is not surprising as earlier re-
ports20a for the reduction of anomeric azides with Zn-AcOH have
led to N,O-acetals in less yields. Dondoni et al.20d have reported
the reduction of C-glycosylated-1-azido sugars with Pd/C-H2 in
tBuOHꢁH2O. But, the use of these conditions in the reduction of
7
8
Figure 2. Hydantocidin and D-glucopyranose analogue of hydantocidin.
Likewise, based on NOE experiments the anomeric configurations
of azides 5b, 5c, 5d, and 5e were confirmed. Further, irradiation
of H-4 proton at d 4.05 in 6a did not show any enhancement of
H-30 methylene protons signal at d 2.18, but enhancement was ob-
served for H-30 signals when irradiation of equatorial proton H-3 at
d 3.57 was done and, as expected,15 the enhancement was small
OBn
OBn
O
O
Pd/CaCO3
BnO
BnO
BnO
H
N
5a
6a
BnO
+
+
EtOH, rt, H2 (1 atm)
2h, 78%
BnO
BnO
O
O
HN
9a
9b
O
1 : 1
OBn
OBn
OBn
O
OBn
O
Pd/CaCO3
BnO
BnO
BnO
H
N
BnO
EtOH, rt, H2 (1 atm)
2h, 83%
HN
10b
OAc
10a
2 : 1
O
OH
R2
R2
Ac2O/Py
O
O
Pd/C/H2 (1 atm)
AcO
AcO
HO
HO
9a
10a
R1
HN
DMAP, 24 h
R1
EtOH, 3-4 days
quantitative
HN
O
O
13a R1 = OAc, R2 = H, 72%
14a R1 = H, R2 = OAc, 80%
11a R1 = OH, R2 = H
12a R1 = H, R2 = OH
OH
R2
OAc
R2
R3
O
O
Ac2O/Py
Pd/C/H2 (1 atm)
HO
HO
H
N
AcO
9b
N
AcO
10b
R1
R1
DMAP, 24 h
O
EtOH, 3-4 days
quantitative
O
11b R1 = OH, R2 = H
12b R1 = H, R2 = OH
13b R1 = OAc, R2 = H, R3 = Ac, 67%
14b R1 = H, R2 = OAc, R3 = H, 74%
Scheme 2. Synthesis of 6,5-fused bicyclic spirolactams.

A. P. John Pal, Y. D. Vankar / Tetrahedron Letters 51 (2010) 2519–2524
2523
5a led to a mixture of products. To overcome these problems we
chose to utilize Pd/CaCO3 as a catalyst22 for the reduction of such
azides. Thus, the treatment of azide 5a with Pd/CaCO3 in EtOH in
the presence of H2 (1 atm) at room temperature afforded the spi-
roaminals 9a and 9b (Scheme 2) in 1:1 ratio and in 78% yield. It
is likely that under these conditions the azide group will first be re-
duced19a to a free amine which will undergo tautomerization
accompanied by pyranose ring opening to form a species having
a free alcohol and an imine. Reclosure to form pyranose ring will
lead to two anomeric amines each of which will cyclize leading
to two spiroaminals viz. 9a and 9b. Likewise, reduction of the man-
nose-derived azido ester 6a in the presence of Pd/CaCO3 gave 2:1
ratio of products 10a and 10b in 83% yield. These benzylated spiro-
lactams 9a, 9b, 10a, and 10b were deprotected using Pd/C in EtOH
in the presence of H2 (1 atm) at room temperature to afford fully
deprotected spirolactams 11a, 11b, 12a, and 12b, respectively, in
quantitative yields, whose structures were confirmed by the spec-
tral analysis of the corresponding acetates obtained from acetyla-
tion with Ac2O/Py. Interestingly, while compound 11b produced
a pentaacetate 13b, other compounds 11a, 12a, and 12b gave the
amides 13a, 14a, and 14b, respectively. All these compounds were
characterized by 1H, 13C NMR and COSY, and spectral data.13a
The stereochemistry at the anomeric center of spiroaminals was
confirmed by NOE experiments. Thus in glucose-derived spiroami-
nal 13a, irradiation of H-9 proton at d 5.40 and H-7 proton at d 3.84
enhanced -NH proton signal at d 8.24 (4.6% and 5.1% NOE, respec-
tively, Fig. 3). Similarly, we confirmed the stereochemistry of spi-
roaminals 14a as an isomer having -NH group in axial position.
In case of compound 14b, irradiation of H-7 proton at d 3.80 and
H-9 proton at d 5.11 enhanced H-4 proton signal at d 2.40 (6.0%
and 3.0% NOE, respectively, Fig. 3), clearly indicating the equatorial
orientation of –NH position in compound 14b. The stereochemistry
of spiroaminal 13b, as isomer with -NAc group in equatorial posi-
tion was also confirmed in an analogous manner.
showed activity against b-galactosidase at 0.4 mM concentration.
These results suggest that these spiroaminals are inhibitors of gly-
cosidases and structural variations of these molecules may im-
prove the activity and selectivity of inhibition.
In conclusion, we have developed a method for the direct con-
version of unstable nitro precursors viz. 1-C-alkyl-1-nitro sugars
into stable amino precursors viz. 1-C-alkyl-1-azido sugars. We
have studied hydrolysis behavior of Michael adducts of 1-nitro
sugars and also SN2-type of azidation reactions. This methodology
gave an easy access to 6,5-fused spiroaminals. Because of the
occurrence of spiroaminal frameworks in natural products of phar-
macological importance, we studied the enzyme inhibition activi-
ties of hydroxy spiroaminals, in which lactam 11a was found to
be selective b-galactosidase inhibitors. Further work to extend
the scope of the present study is in progress.
Acknowledgments
We thank the Department of Science and Technology (DST),
New Delhi for financial support to Y.D.V. in the form of Ramanna
Fellowship (Grant No. SR/S1/RFOC-04/2006). We also thank the
U.G.C., New Delhi for fellowship to A.P.J.P.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2010.03.003.
References and notes
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The inhibitory activities of compounds 11a, 11b, 12a, 12b were
tested against five commercially available enzymes and the results
are summarized in Table 3. The spiroaminals 11a and 11b showed
good inhibition against galactosidases. Compound 11b showed
inhibition against
a-galactosidase (coffee beans) at a concentration
of 77 M as a non-selective glycosidase inhibitor, whereas com-
l
pound 11a was found to be a highly selective b-galactosidase
inhibitor and showed a considerable inhibition at a concentration
of 207 lM. But, mannose-derived spirolactam 12a did not show
any activity against all tested enzymes, only compound 12b
OAc
H
OAc
7H
8
1O0 6
7
1O0 6
H
8
AcO
H
AcO
AcO
5
H 1
N
4. (a) Baumberger, F.; Vasella, A. Helv. Chim. Acta 1986, 69, 1205–1215; (b)
Baumberger, F.; Vasella, A. Helv. Chim. Acta 1986, 69, 1535–1541.
5. Baumberger, F.; Vasella, A.; Schauer, R. Helv. Chim. Acta 1988, 71, 429–445.
4
AcO
5
9
H
AcO
H
3
2
9H
H
2
H
OAc 4
O
HN1
6. Mirza, S.; Vasella, A. Helv. Chim. Acta 1984, 67, 1562–1567.
5.1%
O
3
6.0%
3.0%
H
7. (a) Tamura, R.; Hegedus, L. S. J. Am. Chem. Soc. 1982, 104, 3727–3729; (b) Ono, N.;
Hamamoto, I.; Kaji, A. J. Chem. Soc., Chem. Commun. 1982, 821–822; (c) Ono, N.;
Yanai, T.; Kamimura, A.; Kaji, A. J. Chem. Soc., Chem. Commun. 1986, 1285–1287;
(d) Ono, N.; Hamamoto, I.; Kaji, A. Synthesis 1985, 950–952; (e) Chung, J. Y. L.;
Grabowski, E. J. J.; Reider, P. J. Org. Lett. 1999, 1, 1783–1785; (f) Tamura, R.;
Watabe, K.; Ono, N.; Yamamoto, Y. J. Org. Chem. 1993, 58, 4471–4472; (g) Ono, N.;
Jun, T. X.; Hashimoto, T.; Kaji, A. J. Chem. Soc., Chem. Commun. 1987, 947–948.
8. Vasella, A. Pure Appl. Chem. 1991, 63, 507–518.
4.6%
13a
14b
Figure 3. NOE correlations of compounds 13a and 6a.
Table 3
IC50 M) values for compounds 11a, 11b, 12a, and 12b
9. Aebischer, B.; Bieri, J. H.; Prewo, R.; Vasella, A. Helv. Chim. Acta 1982, 65, 2251–
2271.
(l
10. Mahmood, K.; Vasella, A.; Bernet, B. Helv. Chim. Acta 1991, 74, 1555–1584.
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2002, 1479–1483; (b) Gopal Reddy, B.; Vankar, Y. D. Tetrahedron Lett. 2003, 44,
4765–4767; (c) Gopal Reddy, B.; Vankar, Y. D. Angew. Chem., Int. Ed. 2005, 44,
2001–2004; (d) Jayakanthan, K.; Vankar, Y. D. Tetrahedron Lett. 2006, 47, 8667–
8671; (e) Schmidt, R. R.; Vankar, Y. D. Acc. Chem. Res. 2008, 41, 1059–1073; (f)
Kumar, A.; Rawal, G. K.; Vankar, Y. D. Tetrahedron 2008, 64, 2379–2390.
12. Aebischer, B.; Vasella, A. Helv. Chim. Acta 1983, 66, 789–794.
Entry
Enzyme
-Glucosidase (yeast)
b-Glucosidase (almonds)
-Galactosidase (coffee beans)
b-Galactosidase (bovine)
-Mannosidase (Jack beans)
11a
11b
12a
12b
1
2
3
4
5
a
NIa
NI
NI
207
NI
NI
200
77
160
NI
NI
NI
NI
NI
NI
NI
NI
NI
400
NI
a
a
a
NI: no inhibition at 3 mM concentrations, inhibition studies were carried out at
0.1–0.5 mM concentrations.
13. (a) See the Supplementary data for experimental and spectral details.; (b)
Baumberger, F.; Vasella, A. Helv. Chim. Acta 1983, 66, 2210–2222.

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