N-arylmethylaminoquercitols, a new series of effective antidiabetic agents having α-glucosidase inhibition and antioxidant activity

Article abstract of DOI:10.1016/j.bmcl.2015.04.033

Abstract A new series of N-arylalkylaminoquercitols were synthesized by reductive amination of aminoquercitol bisacetonide 5 and a variety of aryl aldehydes. The targeted N-substituted aminoquercitols having phenolic moiety (7a-7c) displayed significantly enhanced α-glucosidase inhibition, which is 26-32 times more potent than that of the unmodified aminoquercitol 6. In addition, compounds 7a-7c also retained antioxidant activity with relatively more pronounced potency than their original phenolics. This recent finding suggests an approach to develop effective antidiabetic agents by incorporating antioxidative moiety into aminocyclitol core structure.

Full text of DOI:10.1016/j.bmcl.2015.04.033

Bioorganic & Medicinal Chemistry Letters 25 (2015) 2570–2573
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
N-Arylmethylaminoquercitols, a new series of effective antidiabetic
agents having
a-glucosidase inhibition and antioxidant activity
⇑
Wisuttaya Worawalai, Sumrit Wacharasindhu, Preecha Phuwapraisirisan
Natural Products Research Unit, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 January 2015
Revised 7 April 2015
Accepted 11 April 2015
Available online 22 April 2015
A new series of N-arylalkylaminoquercitols were synthesized by reductive amination of aminoquercitol
bisacetonide 5 and a variety of aryl aldehydes. The targeted N-substituted aminoquercitols having phe-
nolic moiety (7a–7c) displayed significantly enhanced
a-glucosidase inhibition, which is 26–32 times
more potent than that of the unmodified aminoquercitol 6. In addition, compounds 7a–7c also retained
antioxidant activity with relatively more pronounced potency than their original phenolics. This recent
finding suggests an approach to develop effective antidiabetic agents by incorporating antioxidative moi-
ety into aminocyclitol core structure.
Keywords:
Aminocyclitol
Diabetes
Ó 2015 Elsevier Ltd. All rights reserved.
Glucosidase
Quercitol
Reductive amination
Patients with diabetes usually suffer from several complications
such as neuropathy, blindness, nephropathy and cardiovascular
diseases. Once prolonged hyperglycemia develops, the over excess
of reactive radicals produced from autooxidation of glucose trig-
gers the dysfunction of microvascular system.1 Therefore, effective
therapy for diabetes and its complications requires simultaneous
suppression of both hyperglycemia and reactive radicals. This
approach prompted us to synthesize a series of quercitylcinna-
mates (Scheme 1) as new antidiabetic agents having dual func-
tight binding with active site of the enzyme.3 This postulation
was also supported by previous reports of N-arylalkylaminocycli-
tols (Scheme 1) as potent glycosidase inhibitors.4 Although a vari-
ety of aminocyclitols have been synthesized,5 other related
bioactivities have rarely been reported. Using the proposed strat-
egy, we herein synthesize a new series of N-arylalkylaminoquerci-
tols and evaluate their
activity.
a-glucosidase inhibition and antioxidation
(+)-proto-Quercitol (1) used as the starting material was
obtained from the stems of Arfeuillea arborescens. The desired
aminoquercitol bisacetonide 5 was synthesized from 1 by applying
the methodology6 previously described (Scheme 3). Initially, the
hydroxyl groups in 1 were protected by Me2C(COMe)2 in the pres-
ence of p-TsOH, therefore exclusively yielding bisacetonide 2
(87%). The remaining hydroxyl group in 2 was thus converted to
the more reactive mesyl group in 3 prior to azidation with NaN3
to afford the azide 4 with inversion of configuration at C-1. This
observation indicated that the replacement of mesyl group by
azide ion (NÀ3 ) possibly proceeds by SN2 fashion. Finally, the
desired product 5 was obtained by azide reduction using LiAlH4.
The deprotected aminoquercitol 6 was also prepared from 5, under
acid condition, for bioactivity evaluation.
Having the desired aminoquercitol bisacetonide 5 in hand, a
series of targeted bioconjugates were synthesized by reductive
amination between 5 and aryl aldehydes (a–c and e–h, Fig. 1).7
Reaction of 5 and 3,5-di-tert-butyl-4-hydroxybenzaldehyde (a),
an antioxidant BHT-like motif, generated N-arylmethylamino-
quercitol 7a, after deprotection of bisacetonide (Table 1). Two
tions; lowering hyperglycemia by inhibiting
a-glucosidase and
scavenging reactive radicals.2 The structure of quercitylcinnamate
comprises (+)-proto-quercitol as a sugar mimic, which is connected
by ester bond to a series of cinnamic acids as radical scavengers.
We found that the installation of these cinnamic moieties can
greatly attenuate glucose level by inhibiting a-glucosidase, in addi-
tion to their inherent antioxidation property. However, the vulner-
ability of ester bond between quercityl and cinnamate moieties
under human condition possibly makes impractical for further
applications.
To circumvent this problem, we turned our attempt to link
quercitol and antioxidative phenolic moieties through C–N amine
bond (Scheme 2), which is expected to be more resistant than ester
linkage. In addition, the replacement of hydroxyl group in
(+)-proto-quercitol by amino residue is expected to enhance a-glu-
cosidase inhibition of the synthesized bioconjugates, possibly by
⇑
Corresponding author. Tel.: +66 2 2187624; fax: +66 2 2187598.
E-mail address: preecha.p@chula.ac.th (P. Phuwapraisirisan).
http://dx.doi.org/10.1016/j.bmcl.2015.04.033
0960-894X/Ó 2015 Elsevier Ltd. All rights reserved.

W. Worawalai et al. / Bioorg. Med. Chem. Lett. 25 (2015) 2570–2573
2571
Our previous work:
OH
quercityl cinnamates
R1
R
R = R1 = tert-Bu
R = OCH3, R1 = H
R = R1 = H
e
f
R2 = H
2 = C=O
a
b
c
O
O
R
(OR)n
CHO
OH
OH
R2
CHO
*
N
S
HO
OH
CHO
CHO
g
Other related works:
N-arylalkylaminocyclitols
h
OH
H
OH
Figure 1. Aldehydes used in reductive amination with aminoquercitol bisacetonide
(5).
HO
HO
N
HO
HO
OH
OMe
OH
N
H
OH
OH
Table 1
Cl
Synthesis of arylalkylaminoquercitols (7a–7c and 7e–7h)
N
OH
N
H
N
N
Ar
HO
HO
n
NH
OH
OH
OH
OH
1) arylaldehyde, NaBH3CN, HOAc, MeOH
2) TFA, MeOH, Dowex 50W-X8 (H+)
N
N
OH
5
Me
N
HO
Scheme 1.
7a-7c, 7g-7h
(n = 1)
7e-7f
(n = 2)
Entry
Arylaldehyde
Product
% Yielda
antioxidant
OH
1
2
3
4
5
6
7
a
b
c
e
f
7a
7b
7c
7e
7f
52
50
65
34
50
85
10
OH
CHO
NH2
n-1
NH
n
OH
OH
OH
g
h
7g
7h
OH
OH
O
HO
a
Isolated yield calculated from two step reactions.
O
HO
O
OH
glucomimic
O
5
OH
1
Br
7
Scheme 2. Retrosynthesis of N-arylalkylaminoquercitols 7.
i, ii
5
NH
OH
OH
OMs
OH
OH
1
OH
OH
O
O
O
O
i
ii
5
3
HO
OH
HO
O
O
v
OH
O
O
7d
1
2
3
Scheme 4. Reagents and conditions: (i) 4-bromobenzyl bromide, TEA, DMF, 72%;
(ii) 1.25 M HCl/MeOH, Dowex 50W-X8 (H+), 29%.
NH2
NH2
N3
OH
OH
O
O
O
O
iii
iv
5. The N-arylethylaminoquercitols (7e–7f) and N-arylmethy-
laminoquercitols (7g–7h) were successfully implemented in a
good yield by reductive amination using NaCNBH3. In addition,
the N-(4-bromobenzyl)aminoquercitol (7d) was also synthesized
by nucleophilic substitution of 5 and 4-bromobenzyl bromide
(Scheme 4).
HO
O
O
O
OH
O
6
4
5
Scheme 3. Reagents and conditions: (i) Me2C(OMe)2, DMF, p-TsOH, 87%; (ii)
MeSO2Cl, Et3N, DMAP, 79%; (iii) NaN3, DMF, 15-crown-5-ether, 100 °C, 75%; (iv)
LiAlH4, 81%; (v) TFA/MeOH, Dowex 50W-X8 (H+), 69%.
All N-arylalkylaminoquercitols 7a–7h were evaluated for
a
-glucosidase inhibition8 and radical scavenging2 (Table 2). Of
arylalkylaminoquercitols examined, 7a (Fig. 2) displayed most
potent inhibition against -glucosidase with IC50 value of
89.1 M. The slightly weaker inhibitions were also observed in
7b (IC50 94.4 M) and 7c (IC50 110.6 M), whose structure com-
prises phenolic moieties. Noticeably, the introduction of antioxida-
tive phenolics to aminoquercitol core structure caused 26–32
related analogues (7b and 7c) having phenolic moiety were also
prepared using identical protocol.
To gain insight into the relationship between N-aryl moiety and
inhibitory effect, other aryl (e and f) and heterocyclic (g and h)
residues were also introduced into aminoquercitol bisacetonide
a
l
l
l

2572
W. Worawalai et al. / Bioorg. Med. Chem. Lett. 25 (2015) 2570–2573
Table 2
concomitantly suppress hyperglycemia and prevent the onset of
complications triggered by over excess of reactive radicals.
Glucosidase inhibition and radical scavenging of synthesized compounds
Compound
a
l
-Glucosidase inhibition (IC50
M)
,
Radical scavenging (SC50
mM)
,
Acknowledgments
6
7a
7b
7c
7d
7e
7f
7g
2890
89.1
94.4
110.6
3145
1350
3010
NAa
NA
NAa
0.4
2.1
16.2
NA
NA
NA
NA
NA
NA
1.4
4.9
NA
This project was financially supported by the Thailand Research
Fund (DBG5380037). W.W. acknowledges the Royal Golden Jubilee
Ph.D. Program (PHD/0025/2553) for fellowship.
Supplementary data
Supplementary data (1H and 13C NMR spectra of compounds
7a–7h) associated with this article can be found, in the online ver-
sion, at http://dx.doi.org/10.1016/j.bmcl.2015.04.033.
7h
AcarboseÒ
480
a
b
c
NTb
NT
NT
References and notes
a
Not active, inhibition against
a-glucosidase less than 30% at concentration of
10 mg/mL or radical scavenging less than 20% at concentration of 5 mg/mL.
b
1. Klein, R. Diab. Care 1995, 18, 258.
2. Rattanangkool, E.; Kittikhunnatham, P.; Damsud, T.; Wacharasindhu, S.;
Phuwapraisirisan, P. Eur. J. Med. Chem. 2013, 66, 296.
Not tested.
3. Bian, X.; Fan, X.; Ke, C.; Luan, Y.; Zhao, G.; Zeng, A. Bioorg. Med. Chem. 2013, 21,
5442.
4. (a) Serrano, P.; Casas, J.; Zucco, M.; Emeric, G.; Egido-Gabás, M.; Llebaria, A.;
Delgado, A. J. Comb. Chem. 2007, 9, 43; (b) Díaz, L.; Casas, J.; Bujons, J.; Llebaria,
A.; Delgado, A. J. Med. Chem. 2011, 54, 2069.
OH
OH
5. Aminocyclitols obtained from fermentation approach: (a) Griffen, J. A.; White, J.
C.; Kociok-Köhn, G.; Lloyd, M. D.; Wells, A.; Arnot, T. C.; Lewis, S. E. Tetrahedron
2013, 69, 5989; (b) Pilgrim, S.; Kociok-Köhn, G.; Lloyd, M. D.; Lewis, S. E. Chem.
Commun. 2011, 4799; (c) de la Sovera, V.; Bellomo, A.; Gonzalez, D. Tetrahedron
2011, 52, 430; (d) Duchek, J.; Adams, D. R.; Hudlicky, T. Chem. Rev. 2011, 111,
4223; routes starting from inositols: (e) Gurale, B. P.; Shashidhar, M. S.;
Gonnade, R. G. J. Org. Chem. 2012, 77, 5801; (f) Murali, C.; Gurale, B. P.;
Shashidhar, M. S. Eur. J. Org. Chem. 2010, 755; (g) Chida, N.; Nakazawa, K.;
Ohtsuka, M.; Suzuki, M.; Ogawa, S. Chem. Lett. 1990, 3, 423; routes starting from
quinic acid: (h) Schwardt, O.; Koliwer-Brandl, H.; Zimmerli, R.; Mesch, S.;
Rossato, G.; Spreafico, M.; Vedani, A.; Kelm, S.; Ernst, B. Bioorg. Med. Chem. 2010,
18, 7239; (i) Prazeres, V. F. V.; Castedo, L.; Gonzalez-Bello, C. Eur. J. Org. Chem.
2008, 3991; (j) Gonzalez-Bello, C.; Castedo, L.; Canada, F. J. Eur. J. Org. Chem.
2006, 1002; (k) Shing, T. K. M.; Wan, L. H. Angew. Chem., Int. Ed. Engl. 1995, 34,
1643.
NH
BHT
OH
OH
HO
HO
O
OH
α
-tocopherol (vitamin E)
7a
Figure 2.
times more improved inhibition than the unmodified starter (6).
Conversely, the incorporation of heterocyclic and other aryl resi-
dues into aminoquercitol, led to very weak or no inhibitions in
7d–7h.
On evaluation of radical scavenging activity, the phenolic-incor-
porated aminoquercitols 7a–7c showed SC50 values in range of
0.4–16 mM whereas compounds 7d–7h were not active.
Interestingly, the scavenging activities of 7a–7c were 2–3 times
higher than those of their original phenolics (a–c).
6. (a) Wacharasindhu, S.; Worawalai, W.; Rungprom, W.; Phuwapraisirisan, P.
Tetrahedron Lett. 2009, 50, 2189; (b) Worawalai, W.; Wacharasindhu, S.;
Phuwapraisirisan, P. Med. Chem. Commun. 2012, 3, 1466.
7. General procedure for reductive amination and deprotection of bisacetonide: To a
solution of aminoquercitol bisacetonide
0.1 mmol of 5) under an atmosphere of N2 was added sodium
cyanoborohydride (2 equiv), acetic acid (4 L/0.05 mmol of 5) and aldehyde a
5 (1 equiv) in methanol (1.0 mL/
l
(1.5 equiv). After stirring at ambient temperature for 24 h, the reaction mixture
was quenched with water, concentrated and extracted twice with EtOAc. The
combined organic layers were washed with brine, dried over anhydrous Na2SO4
and concentrated under reduced pressure to afford crude product, which was
subsequently purified by silica gel or Sephadex LH-20 column chromatography
to afford the bisacetonide.
Noticeably,
a-glucosidase inhibitory potency of N-arylmethy-
To
a solution of the bisacetonide in 5% TFA–MeOH was stirred at room
laminoquercitols 7a–7c is likely to be depend on antioxidative
moieties introduced. This observation was supported by the most
temperature for 2 h. The reaction mixture was evaporated to dryness, dissolved
in H2O, loaded onto Dowex 50W-X8 (H+) column, which was initially eluted
with H2O followed by 50% NH4OH. Fractions eluted with 50% NH4OH were
lyophilized to give 7a. Other N-arylalkylaminoquercitols (7b–7c and 7e–7h)
were also synthesized using the aforementioned protocol.
potent
most effective antioxidative motif a (SC50 1.4 mM). In fact, the
structure is nearly identical to BHT (butylhydroxytoluene,
a-glucosidase inhibitor 7a, whose structure comprises the
a
N-(3,5-Di-tert-butyl-4-hydroxybenzyl)-epi-aminoquercitol (7a): Yellow oil. 1H
NMR (CD3OD, 400 MHz) d 7.05 (br s, 2H), 4.00 (s, 1H), 3.66 (d, J = 12.0 Hz, 1H),
3.56 (d, J = 12.0 Hz, 1H), 3.43 (dd, J = 8.0, 8.0 Hz, 1H), 3.26 (m, 1H), 3.15 (dd,
J = 12.0, 4.0 Hz, 1H), 2.59 (br d, J = 12.0 Hz, 1H), 1.86 (m, 1H), 1.56 (m, 1H), 1.32
(br s, 18H); 13C NMR (CD3OD, 100 MHz) d 154.6, 139.4, 130.8, 126.3, 76.4, 75.1,
72.0, 70.8, 55.0, 51.5, 35.6, 34.1, 30.8, 30.8; HRMS m/z 382.2582 [M+H]+ (calcd
for C21H36NO5, 382.2593).
Fig. 2), a well recognized antioxidant used in a wide variety of
applications. Although various N-arylalkylaminocyclitols have
been synthesized,3,4,9 none of them has been examined for radical
scavenging activity. The finding of enhanced a-glucosidase inhibi-
tion of N-arylmethylaminoquercitols 7a–7c suggested a possible
approach capable of improving this inhibition in other aminocycli-
tols by incorporating potent antioxidative motifs such as
pherol (vitamin E, Fig. 2).
In summary, we have synthesized a new series of N-arylalky-
laminoquercitols (7a–7h) by reductive amination of aminoquerci-
tol bisacetonide 5 and arylaldehydes (a–h). The incorporation of
phenolic moieties (a–c) into aminoquercitol core structure not
N-(4-Hydroxy-3-methoxybenzyl)-epi-aminoquercitol (7b): Pale yellow oil. 1H
NMR (CD3OD, 400 MHz) d 7.03 (br s, 1H), 6.85 (d, J = 8.0 Hz, 1H), 6.79 (d,
J = 8.0 Hz, 1H), 4.14 (br s, 1H), 3.97 (m, 1H), 3.90 (m, 1H), 3.86 (s, 3H), 3.55 (t,
J = 10.0 Hz, 1H), 3.38 (m, 1H), 3.29 (m, 1H), 2.97 (br d, J = 12.0 Hz, 1H), 2.01 (m,
1H), 1.78 (m, 1H); 13C NMR (CD3OD, 100 MHz) d 149.3, 148.0, 127.6, 123.4,
116.5, 114.0, 76.0, 74.5, 71.5, 69.9, 56.6, 55.3, 50.4, 32.6; HRMS m/z 300.1440
[M+H]+ (calcd for C14H22NO6, 300.1447).
a-toco-
N-(4-Hydroxybenzyl)-epi-aminoquercitol (7c): White solid. 1H NMR (D2O,
400 MHz) d 7.01 (d, J = 8.0 Hz, 2H), 6.61 (d, J = 8.0 Hz, 2H), 3.93 (br s, 1H),
3.61–3.71 (m, 2H), 3.13–3.32 (m, 3H), 2.77 (br d, J = 12.0 Hz, 1H), 1.80 (br s, 1H),
1.43 (m, 1H); 13C NMR (D2O, 100 MHz) d 156.6, 130.9, 126.3, 116.0, 74.2, 72.5,
69.7, 68.7, 52.9, 48.5, 30.9; HRMS m/z 270.1339 [M+H]+ (calcd for C13H20NO5,
270.1341).
only markedly improved
enhanced radical scavenging activity. Their unique dual functions
would make them more intriguing for diabetes therapy as they
a-glucosidase inhibition but also

W. Worawalai et al. / Bioorg. Med. Chem. Lett. 25 (2015) 2570–2573
2573
N-(4-Bromobenzyl)-epi-aminoquercitol (7d): White solid. 1H NMR (D2O+2 drops
of CD3OD, 400 MHz) d 7.36 (d, J = 8.0 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 3.94 (br s,
1H), 3.63–3.74 (m, 2H), 3.21–3.34 (m, 2H), 3.15 (m, 1H), 2.70 (br d, J = 11.6 Hz,
1H), 1.81 (m, 1H), 1.42 (q, J = 12.0 Hz, 1H); 13C NMR (D2O+2 drops MeOD,
100 MHz) d 135.3, 131.8, 130.8, 121.5, 74.2, 72.5, 69.8, 68.9, 53.1, 48.5, 31.3;
HRMS m/z 332.0498, 334.0479 [M+H]+ (calcd for C13H1979BrNO4, 332.0497 and
N-(3-Methylpyridyl)-epi-aminoquercitol (7g): Pale yellow oil. 1H NMR (CD3OD,
400 MHz) d 8.64 (br s, 1H), 8.55 (d, J = 4.0 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.51
(dd, J = 8.0, 4.0 Hz, 1H), 4.11–4.23 (m, 3H), 3.57 (t, J = 8.0 Hz, 1H), 3.47 (m, 1H),
3.37 (m, 1H), 3.18 (br d, J = 12.0 Hz, 1H), 2.10 (m, 1H), 1.84 (m, 1H); 13C NMR
(CD3OD, 100 MHz) d 149.6, 148.8, 138.3, 130.8, 124.2, 74.3, 72.7, 69.7, 68.2,
54.6, 46.2, 30.7; HRMS m/z 255.1339 [M+H]+ (calcd for C12H19N2O4, 255.1345).
N-(2-Methylthiophenyl)-epi-aminoquercitol (7h): White solid. 1H NMR (CD3OD,
400 MHz) d 7.20 (br s, 1H), 6.86–6.91 (m, 2H), 3.88–3.97 (m, 3H), 3.42 (dd,
J = 9.2, 9.2 Hz, 1H), 3.25 (m, 1H), 3.12 (br d, J = 9.6 Hz, 1H), 2.58 (br d,
J = 12.0 Hz, 1H), 1.83 (br d, J = 9.6 Hz, 1H), 1.53 (q, J = 12.0 Hz, 1H); 13C NMR
(CD3OD, 100 MHz) d 143.8, 127.8, 126.9, 125.8, 76.3, 75.0, 72.0, 71.0, 54.6, 45.5,
34.2; HRMS m/z 260.0951 [M+H]+ (calcd for C11H18NO4S, 260.0957).
C
13H1981BrNO4, 334.0477).
N-Phenylethyl-epi-aminoquercitol (7e): Colorless oil. 1H NMR (CD3OD, 400 MHz)
d 7.12–7.23 (m, 5H), 3.97 (br s, 1H), 3.43 (dd, J = 9.2, 9.2 Hz, 1H), 3.31 (m, 1H),
3.19 (m, 1H), 2.78–2.99 (m, 5H), 1.89 (m, 1H), 1.61 (q, J = 12.0 Hz, 1H); 13C NMR
(CD3OD, 100 MHz) d 139.6, 129.8, 129.7, 127.8, 76.0, 74.5, 71.5, 70.1, 56.0, 48.3,
35.3, 32.7; HRMS m/z 268.1543 [M+H]+ (calcd for C14H22NO4, 268.1549).
N-(Phenylhydroxyethyl)-epi-aminoquercitol (7f): Yellow oil. 1H NMR (D2O,
8.
a-Glucosidase inhibition of synthesized compounds was examined using our
400 MHz)
d 7.25–7.32 (m, 5H), 4.89 (dd, J = 12.0, 4.0 Hz, 1H), 4.08 (br d,
recent protocol. (a) Worawalai, W.; Wacharasindhu, S.; Phuwapraisirisan, P.
Bioorg. Med. Chem. Lett. 2014, 24, 5530; (b) Damsud, T.; Grace, M. H.;
Adisakwattana, S.; Phuwapraisirisan, P. Nat. Prod. Commun. 2014, 9, 639.
J = 12.0 Hz, 1H), 3.11–3.44 (m, 6H), 2.03 (m, 1H), 1.71 (m, 1H); 13C NMR (D2O,
100 MHz) d 139.6, 129.1, 129.1, 126.1, 73.8, 71.9, 69.1, 67.6, 67.4, 54.8, 50.9,
29.4; HRMS m/z 284.1497 [M+H]+ (calcd for C14H22NO5, 284.1498). Note that the
ketone group in phenylglyoxal (f) was also reduced to chiral secondary alcohol
by NaCNBH3, upon reductive amination with aminoquercitol bisacetonide 5.
Thus, the actual structure of 7f was shown below. Note that only single isomer
of 7f was obtained after purification by cationic exchange resin. An attempt to
determine the configuration of newly generated chiral center was not carried
9. (a) Łysek, R.; Schütz, C.; Favre, S.; O’Sullivan, A. C.; Pillonel, C.; Krülle, T.; Jung, P.
M. J.; Clotet-Codina, I.; Esté, J. A.; Vogel, P. Bioorg. Med. Chem. 2006, 14, 6255; (b)
Łysek, R.; Schütz, C.; Vogel, P. Bioorg. Med. Chem. Lett. 2005, 15, 3071; (c)
Bøjstrup, M.; Lundt, I. Org. Biomol. Chem. 2005, 3, 1738; (d) Dickson, L. G.; Leroy,
E.; Reymond, J.-L. Org. Biomol. Chem. 2004, 2, 1217; (e) Kleban, M.; Jäger, V.
ChemBioChem 2001, 2, 365; (f) Uchida, C.; Kimura, H.; Ogawa, S. Bioorg. Med.
Chem. 1997, 5, 921; (g) Horii, S.; Fukase, H.; Matsuo, T.; Kameda, Y.; Asano, N.;
Matsui, K. J. Med. Chem. 1986, 29, 1038.
out because 7f showed very weak
a-glucosidase inhibition and no radical
scavenging activity.
OH
NH
*
7f
OH
OH
HO
OH