Synthesis and photochromic properties of configurationally varied azobenzene glycosides

Article abstract of DOI:10.1002/open.201402010

Spatial orientation of carbohydrates is a meaningful parameter in carbohydrate recognition processes. To vary orientation of sugars with temporal and spatial resolution, photosensitive glycoconjugates with favorable photochromic properties appear to be op

Full text of DOI:10.1002/open.201402010

DOI: 10.1002/open.201402010
Synthesis and Photochromic Properties of
Configurationally Varied Azobenzene Glycosides
Vijayanand Chandrasekaran, Eugen Johannes, Hauke Kobarg, Frank D. Sçnnichsen, and
Thisbe K. Lindhorst*[a]
Spatial orientation of carbohydrates is a meaningful parameter
in carbohydrate recognition processes. To vary orientation of
sugars with temporal and spatial resolution, photosensitive
glycoconjugates with favorable photochromic properties
appear to be opportune. Here, a series of azobenzene glyco-
sides were synthesized, employing glycoside synthesis and
Mills reaction, to allow “switching” of carbohydrate orientation
by reversible E/Z isomerization of the azobenzene N=N double
bond. Their photochromic properties were tested and effects
of azobenzene substitution as well as the effect of anomeric
configuration and the orientation of the sugar’s 2-hydroxy
group were evaluated.
Introduction
Photoswitchable glycoconjugates have recently received in-
creasing attention for their potential of spatial and temporal
control of carbohydrate recognition.[1] This is because photo-
isomerization of such “sweet switches” allows for a reversible
shifting between two structurally different states in which car-
bohydrate orientation is significantly altered. Thus, photo-
switchable glycoconjugates might be utilized on surfaces to
control cell adhesion or to influence other processes of cell
biology.[2] Moreover, they may eventually lead to the develop-
ment of designer surfaces for further applications.[3]
Figure 1. Irradiation of azobenzene glycosides effects E/Z isomerization ac-
companied by a significant change in orientation of the ligated carbohy-
drate moiety.
We have shown earlier that, among photosensitive glyco-
conjugates, the azobenzene glycosides are suitable tools in the
context of molecular switching.[4] In azobenzene glycosides,
the well-known azobenzene substructure serves as a reliable
photoresponsive unit that is glycosidically attached to a specific
carbohydrate glycone moiety. Irradiation of the planar and
more stable E-form of an azobenzene glycoside with UV light
(lꢀ365 nm) effects transition to the bent Z isomer.[5] By expo-
sure to visible light (l>440 nm) or by thermal equilibration,
the azobenzene Z isomer relaxes back to the E-form with
a half-life t1/2 which is an individual parameter of a specific
azobenzene derivative.[6] Hence, E/Z isomerization of the N=N
double bond in azobenzene glycosides can be employed to
effect a considerable change in the spatial orientation of the
conjugated sugar moiety (Figure 1).
For the application of photosensitive azobenzene glycosides,
the kinetics of photoswitching are critical. The photoinduced
E!Z isomerization of azobenzene derivatives is known to be
fast and can be performed in a few femtoseconds using an ap-
propriate light source.[6] The rate of the Z!E relaxation pro-
cess, on the other hand, greatly depends on the structure of
the molecule. Here, both slow and fast Z!E back isomeriza-
tion can be desired depending on the planned application.
Slow Z!E isomerization, for example, is required to investigate
the two photoisomeric states of an azobenzene glycoside in
a biological assay independently of each other. Fast relaxation
in turn is crucial for the application of azobenzene derivatives
in real-time information-transmitting systems.
[a] Dr. V. Chandrasekaran, E. Johannes, H. Kobarg, Prof. Dr. F. D. Sçnnichsen,
Prof. T. K. Lindhorst
Otto Diels Institute of Organic Chemistry
Christiana Albertina University of Kiel
Otto-Hahn-Platz 3/4, 24118 Kiel (Germany)
E-mail: tklind@oc.uni-kiel.de
For Z!E back isomerization of azobenzene glycosides, it is
especially interesting to test the influence of configurational
characteristics; in particular, the relevance of the configuration
at the 2-position of the sugar ring, adjacent to the anomeric
center, which often influences the properties of glycosides spe-
cifically. Secondly, the impact of the anomeric configuration on
Z!E relaxation has to be tested. Consequently, we have com-
menced a corresponding study on the photochromic proper-
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/open.201402010.
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This is an open access article under the terms of the Creative Commons
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acetylation[11] gave the next two
target glycosides 3 and 6, and
treatment with LiOH in a subse-
quent step delivered the unpro-
tected
o’-carboxyl-substituted
azobenzene glycosides 2 and 5.
Notably, the water solubility of
the methyl esters 3 and 6 was
better than that of the carboxyl-
ic acids 2 and 5. Overall, the syn-
thesis of the first two sets of
azobenzene glycosides, 1–3 and
4–6 required only a handful of
high-yielding steps, furnishing
Figure 2. Target azobenzene glycosides: Configurational characteristics were systematically varied to study their
effect on the photochromic properties of the respective molecule.
ties of azobenzene glycosides, mainly employing a series of
nine representatives, the a-d-mannosides 1–3, the b-d-gluco-
sides 4–6, and the a-d-glucosides 7–9 (Figure 2). Substituents
at the azobenzene moiety were expected to alter the photo-
chromic properties of the respective glycosides but also were
installed to influence solubility as well as to provide a function-
al handle for later conjugation.
the final products as colored crystalline compounds.
The series of synthetic azobenzene glycosides was comple-
mented by a-d-glucosides 7–9. These glucosides are represen-
tatives of the 1,2-cis-glycoside type, and therefore more diffi-
cult to synthesize stereoselectively. A number of methods pro-
viding a stereospecific access to a-glucosides have been intro-
duced,[12] often requiring a higher number of synthetic steps.
We therefore refrained from a glycosylation approach for the
synthesis of 7–9. Instead Mills reaction[13] was utilized compris-
ing acid-promoted condensation of amino-substituted aryl de-
Results and Discussion
Synthesis of azobenzene glycosides
Synthesis of the desired azobenzene glycosides
(Figure 2) started with the preparation of the 1,2-
trans-configured a-d-mannosides 1–3 and the 1,2-
trans-configured b-d-glucosides 4–6. Azobenzene
glycosides of the 1,2-trans-type can be obtained in
a stereospecific glycosylation reaction, employing an
O-acylated glycosyl donor and the appropriate azo-
benzene alcohol. The neighbouring group participa-
tion of the 2-O-acyl group of the sugar ring ensures
the stereospecific course of the glycosylation reac-
tion.[7] Thus, the O-acetylated glycosyl trichloroacet-
imidates 10[8] and 11,[9] respectively, were employed
for glycosylation of commercially available 4-hydroxy-
azobenzene (12) according to Schmidt’s procedure[10]
in a Lewis acid-catalyzed reaction. We have described
this approach for the synthesis of the
a-configured mannoside 13 earlier,[4] and here it was
extended to the synthesis of 14. Deprotection under
Zemplꢁn conditions[11] led to the known a-manno-
side 1[4] and to its analogue, the b-glucoside 4, the
first two target glycosides of this study (Scheme 1).
Next we aimed at introducing a carboxyl group at
the azobenzene aglycone moiety in order to improve
water solubility of the azobenzene glycosides. The re-
quired carboxyl-substituted azobenzene derivative
15, o-(p-hydroxyphenylazo)benzoic acid (HABA), is
commercially available. For glycosylation, it was con-
verted into its methyl ester 16, and then again Lewis
Scheme 1. Synthesis of azobenzene glycosides 1–6. a) BF3·Et2O, CH2Cl2, 08C!RT, 13 (with
12: 81%), 14 (with 12: 73%), 17 (with 16: 84%), 18 (with 16: 79%); b) NaOMe, MeOH,
RT, 1 (92%), 3 (89%), 4 (90%), 6 (83%); c) MeOH/HCl, reflux, 5 h, 85%; d) LiOH, THF/H2O
acid-promoted reaction with glycosyl donors 10 and
11, respectively, led to the methoxycarbonyl-substi-
tuted azobenzene glycosides 17 and 18. Zemplꢁn de- (2:1), RT, 2 (93%), 5 (91%).
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molecule, which displays one signal set for both
mannosyl moieties in its NMR spectra.
Photochromic properties
With this collection of new azobenzene glycosides in
hand, E!Z photoisomerization was studied. Photo-
stationary states (PSS) were reached after irradiation
at 365 nm for approx. 30 min. Resulting E/Z ratios
1
were determined in H NMR spectra, as E and Z iso-
mers display well-separated and easily distinguisha-
ble resonances for the aromatic and the anomeric
protons (Table 1). Thus, E/Z ratios of the isomeric mix-
tures in the ground state (GS) as well as in the PSS
were quantified by integration of the respective NMR
peaks. It is noteworthy that the solutions used for
NMR spectroscopy had millimolar concentrations
(ꢀ40 mmol). On the other hand, rate constants k and
half-lives t1/2 of thermal Z!E back isomerization
were determined by UV/Vis spectroscopy employing
50 mm solutions in DMSO (cf. Supporting Informa-
tion). The photochromic data obtained for the syn-
thetic azobenzene glycosides are collected in Table 2.
As expected, all azobenzene glycosides are completely
Scheme 2. Synthesis of azobenzene glycosides 7, 8, and 9. a)Acetic acid, RT, 7 (96%);
b) oxone, CH2Cl2/H2O (16:20), RT; c) pyridine, acetic anhydride, RT, 22 (89% over two
steps); d) NaOMe, MeOH, RT, overnight, 96%; e) LiOH, THF/H2O (2:1), RT, 18 h, 95%.
rivatives and nitrosoarenes. Thus, synthesis of the target a-azo-
benzene glucosides started with p-aminophenyl a-d-glucoside
19, which can be obtained by catalytic reduction of commer-
cially available p-nitrophenyl a-d-glucoside in a quantitative re-
action (Scheme 2).[14] Acid-catalyzed condensation of 19 with
nitrosobenzene delivered the unprotected target glucoside 7
in high yield. Likewise, target glucoside 8 was derived from
condensation of 19 with the nitrosobenzene derivative 21,
which was obtained from its carboxylic acid ester 20[15] and
employed in situ. In order to facilitate purification of the con-
densation product, it was submitted to O-acetylation, using
acetic anhydride in pyridine to yield the fully protected gluco-
side 22, which could be easily purified. Then, de-O-acetylation
furnished the methoxycarbonyl-substituted glucoside 9 in pure
form, and subsequent saponification of 9 with LiOH gave the
carboxylic acid derivative 8.
E-configured in their GS within the experimental error (Table 2).
Their UV/Vis spectra display very similar absorption maxima.
The carbohydrate moiety does not alter these electronic prop-
erties owing to lack of conjugation. The different o’-substitu-
ents influence the maxima somewhat, their effect on the ther-
mal Z!E back isomerization rate, however, is much more pro-
In addition to the nine target azobenzene glycosides 1–9,
we were interested in the properties of p’-hydroxy-substituted
azobenzene glycosides, which were derived from the azoben-
zene acceptor diol 23 by monoglycosylation. Diol 23 was pre-
pared according to the literature (Scheme 3).[16] Thus, O-acety-
lated glycosides 24 and 25 were received employing 10 and
11, respectively, as the glycosyl donors. Yields were limited in
this case, due to only partial glycosylation of diol 23. Usual de-
protection of 24 and 25 gave the OH-free azobenzene glyco-
sides 26 and 27, respectively. We also aimed at the divalent
azobenzene mannnoside 29, as it is a promising antagonists of
the mannose-specific bacterial lectin FimH.[17] When an appro-
priate amount of mannosyl donor 10 was employed in the gly-
cosylation reaction with 23, a mixture of the mono- and bis-a-
mannosylated azobenzene derivatives 24 and 28 was obtained
in 37% and 31% respective yields after separation by column
chromatography. Subsequent de-O-acetylation proceeded in
high yields. The bis-glycosylated glycoside 29 is a symmetric
Scheme 3. Synthesis of azobenzene glycosides 26, 27, and 29. a) BF3·Et2O,
CH2Cl2, 08C!RT, 24 (37%), 25 (31%), 28 (31%); b) NaOMe, MeOH, RT, 26
(88%), 27 (89%), 29 (93%).
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monomeric glycosides are present, giving rise to sharp NMR
resonances (Figure 3a). Partial and dynamic association is ap-
parent for 8 at intermediate concentrations where strong ex-
change-broadened resonances in particular for the o’-substitut-
ed phenyl ring protons can be observed. At high concentra-
tions, all resonances are again observed with reasonable line
widths owing to the presence of a stable aggregate (Fig-
ure 3c). Most strongly, this aggregation behavior is observed in
the NMR-determined PSS ratios
Table 1. Chemical shifts d [ppm] of anomeric protons (H-1) of E- and Z-
configured azobenzene glycosides.[a]
H-1
1
1
3
4
5
6
7
8
9
29
E isomer 5.54 5.53 5.53 5.04 4.99 5.00 5.55 5.57 5.57 5.51
Z isomer 5.34 5.30 5.31 4.80 4.78 4.80 5.35 5.34 5.35 5.34
[a] 1H NMR ([D6]DMSO, 500 MHz).
of the o’-carboxylates 2, 5, and
Table 2. Comparison of photochromic properties of synthesized azobenzene glycosides with different types of
azobenzene substitutions, in particular carboxyl (CO2H) and methoxycarbonyl (CO2Me).
8. The differences in these show
a further dependency on the
anomeric configuration and the
configuration at C-2 of the sugar
ring, presumably reflecting close
steric contact of the carbohy-
drate moieties in the associated
form of the respective azoben-
zene glycosides.
Compd
Substituent
GS E/Z ratios
by NMR[a] (e)[b]
lmax(E), lmax(Z)
[nm][c]
t1/2
[h][d]
PSS E/Z ratios
by NMR[a] (e)[b]
PSS E/Z ratios
by UV/Vis[c]
1 (a-man)
4 (b-glc)
7 (a-glc)
2 (a-man)
5 (b-glc)
8 (a-glc)
3 (a-man)
6 (b-glc)
9 (a-glc)
26 (a-man)
29
H
H
H
99:1 (25907)
98:2 (23274)
99:1 (15804)
99:1 (29362)
99:1 (28335)
98:2 (13715)
98:2 (21694)
98:2 (18722)
99:1 (16943)
98:2 (19804)
98:2 (18810)
347, 440
347, 439
356, 439
341, 423
337, 425
341, 424
345, 426
346, 425
345, 426
363, 480
358, 446
89
94
36
2
4
2.5
5
5
2
–
24
3:97 (2635)
4:96 (1704)
2:98 (1712)
85:15 (3106)
41:59 (2521)
76:24 (1407)
10:90 (3452)
39:61 (2071)
45:55 (1734)
–
5:95
5:95
5:95
25:75
25:75
30:70
20:80
20:80
20:80
–
ortho’-CO2H
ortho’-CO2H
ortho’-CO2H
ortho’-CO2Me
ortho’-CO2Me
ortho’-CO2Me
para’-OH
para’-a-man
A detailed characterization of
this unexpected observation and
delineation of the type of aggre-
gates is beyond the scope of
this synthetic paper and is the
focus of ongoing research. Nev-
ertheless, similar effects of o-sub-
stitution have been reported in
the literature.[18] Here, the forma-
tion of inter- as well as intramo-
lecular hydrogen bonds between
5:95 (1395)
5:95
1
[a] E/Z ratios are based on the integrals of the respective anomeric protons H-1 in the H NMR spectrum (at mil-
limolar concentration, namely 10 mg sample in 600 mL [D6]DMSO, 500 MHz). [b] e: Extinction coefficient
[Lmolꢁ1 cmꢁ1]. [c] UV/Vis absorption maxima lmax(E) and lmax(Z) [nm]. [d] Half-life t1/2 as determined by UV/Vis
spectroscopy (50 mm samples in DMSO). PSS=Photostationary states. [e] Rounded values based on estimated
accuracy of ꢂ5% (cf. Supporting Information).
nounced. Inclusion of a carboxyl- or methoxycarbonyl group
shortens the half-life t1/2 from ~90 h to ~2 h and 5 h, respec-
tively. These shorter life times of a less-stable Z isomer suggest
that the barrier for thermal relaxation is lowered. This can be
clearly seen in case of the p’-OH-substituted azobenzene man-
noside 26. Here, thermal Z!E back isomerization was too fast
to allow monitoring by NMR spectroscopy. This finding is in
line with reports from the literature, showing that p-hydroxy-
substituted azobenzene derivatives are characterized by fast ki-
netics of thermal relaxation of the Z isomer, leading to relaxa-
tion times in the millisecond range.[6,18] This feature is also em-
phasized by our observation that the p’-OH-substituted azo-
benzene glucoside 27 behaves exactly the same as the analo-
gous mannoside 26 (Scheme 3).
azobenzene substituents (e.g., hydroxy or carboxyl) and the
azobenzene N2 moiety similarly affect the thermal Z!E isomer-
Most strikingly, significant substituent effects are observed
in the PSS E/Z ratios determined by NMR spectroscopy. These
further deviate significantly from the PSS ratio estimated from
the UV data. An o’-substitution reduces conversion to the
Z isomer from near completeness to about 80% under UV con-
ditions. Under NMR conditions, in particular conversion of the
o’-carboxyl-substituted compounds is moderately to severely
hindered (15% Z isomer for 2, 24% for 8, and 59% for 5) de-
pending on the sugar moiety.
Figure 3. Aromatic region of 1H NMR spectra of 8 in [D6]DMSO at concentra-
tions of a) 5 mm, b) 500 mm and c) 50 mm. Spectra were acquired with
a Bruker Avance II 600 MHz spectrometer, using a standard 1D experiment
with excitation sculpting for solvent line suppression acquiring 64 scans. In
c) and a) sharp resonances are obtained for the monomeric and aggregated
compound, respectively. At intermediate concentration (b), broadening is
observed most pronouncedly for the o-carboxyl-substituted phenyl ring of
the azobenzene moiety, owing to the presence of intermediate timescale ex-
change between monomeric and aggregated species.
The source of these surprising results lies in differing solu-
tion properties of the azobenzene glycosides as highlighted by
the exemplary 1H NMR spectra of the a-d-glucoside
8
(Figure 3). At low concentration (UV conditions), unassociated
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ization. The energy barrier of Z!E relaxation can be signifi-
cantly lowered when azobenzene substituents favor a hydra-
zone-type distribution of electron density and thus promote
a tautomeric form of the molecule by which thermal Z!E re-
covery is facilitated. It was also suggested that substituents at
the azobenzene substructure can alter the isomerization mech-
anism (rotation versus inversion mechanism).[6,19,20] Moreover,
azobenzene substitution can influence pH sensitivity of photo-
isomerization and solvent dependency of isomerization.[21] Our
results strongly suggest, that substitution may also dramatical-
ly affect the tendency of the compounds to interact via p–p
stacking or hydrogen-bond mechanisms, and thus may lead to
strongly varying photochromic properties.
Figure 4. Numbering of hydrogen and carbon atoms for assignment of NMR
data exemplified for mannoside 3.
pass filters were obtained from laser components. IR spectra
were measured with a PerkinElmer FT-IR Paragon 1000 (ATR)
spectrometer. ESI mass spectra were recorded on a Mariner in-
strument 5280. MALDI-TOF mass spectra were recorded on
a Bruker Biflex III instrument with 19 kV acceleration voltage,
and 2,5-dihydroxybenzoic acid (DHB) was used as a matrix.
High-resolution mass spectra (HRMS) were measured using
a Thermo Scientific LTQ Velos Orbitrap mass spectrometer
equipped with nano-electrospray source in positive ion mode.
Elemental analyses were performed using a Euro Vector CHNS-
O-element analyzer (Euro EA 3000) at the Institute of Inorganic
Chemistry, Christiana Albertina University of Kiel.
Conclusions
While substitution effects in azobenzene glycosides are difficult
to predict, it can be concluded that indeed the anomeric link-
age of a glycoside (cf. 5 versus 8) as well as the configuration
of the 2-OH group (cf. 3 versus 6) can be crucial for the photo-
isomerization behavior, possibly via steric differences in associ-
ated glycosides. These two important characteristics of a glyco-
side thus provide additional parameters to regulate the photo-
chromic properties of this class of “sweet switches”, which can
be employed to facilitate future applications in the field of car-
bohydrate recognition.
Irradiation of E-configured azobenzene glycosides: The re-
spective E-configured azobenzene glycoside (ꢀ10 mg) was
dissolved in [D6]DMSO (600 mL) in a NMR tube and irradiated
for 30 min at 365 nm. Photostationary states (PSS) were
reached after approx. 30 min. Then, the sample was kept in
Experimental Section
1
the dark, and H NMR spectroscopy was performed immediate-
General methods: p-Hydroxyazobenzene and o-(p-hydroxy-
phenylazo)benzoic acid were purchased from Sigma–Aldrich
and used without further purification. Air/moisture-sensitive re-
actions were carried out under nitrogen in dry glassware. Thin-
layer chromatography was performed on silica gel plates (GF
254, Merck), using UV detection and subsequent charring with
10% sulfuric acid in EtOH followed by heat treatment at
~1808C. Flash chromatography was performed on silica gel 60
(Merck, 230–400 mesh, particle size 0.040–0.063 mm) using dis-
tilled solvents. Melting points (mp) were determined on
a Bꢂchi 510 apparatus (Flawil, Switzerland). Optical rotations
were measured with a PerkinElmer 241 polarimeter (sodium D-
ly afterwards. NMR data of Z isomers are given in the Support-
ing Information. In analogy, for UV/Vis spectroscopy, the E-con-
figured azobenzene glycoside was dissolved in DMSO in a UV
cuvette, irradiated for 30 min at 365 nm, and UV/Vis spectra
were recorded immediately afterwards. Extinction coefficients
e were deduced from UV/Vis spectra measured at five different
concentrations (10 mm, 20 mm, 30 mm, 40 mm and 50 mm; for de-
tails see the Supporting Information).
Half-life determination: Half-life t1/2 determination of thermal
Z!E back isomerization was determined using UV/Vis spec-
troscopy (for details see the Supporting Information).
1
line: 589 nm, length of cell: 1 dm) in the solvents indicated. H
and 13C NMR spectra were recorded on Bruker DRX-500 and
AV-600 spectrometers at 300 K. Chemical shifts d are reported
relative to internal tetramethylsilane (d=0.00 ppm) or D2O
(d=4.76 ppm) in ppm. Full assignment of the peaks was ach-
E-p-(Phenylazo)phenyl a-d-mannopyranoside (1): NaOMe
(15 mg) was added under N2 atmosphere to a solution of the
protected glycoside 13 (600 mg, 1.14 mmol) in dry MeOH
(6 mL), and the reaction mixture was stirred at RT overnight.
The reaction mixture was neutralized with Amberlite IR 120 ion
exchange resin and was filtered. The filtrate was evaporated
under reduced pressure, and the crude product purified by
flash column chromatography (10% MeOH in CH2Cl2) to yield
deprotected 1. Recrystallization from MeOH gave a pale yellow
solid (376 mg, 1.04 mmol, 92%): mp: 183–1858C; Rf =0.33
(CH2Cl2/MeOH, 4:1); [a]2D0 = +1.40 (c=1.0, DMSO); 1H NMR
(500 MHz, [D6]DMSO): d=7.86 (d, J=8.7 Hz, 2H, H-9, H-11),
7.82 (d, J=7.7 Hz, 2H, H-14, H-18), 7.56 (t, J=7.6 Hz, 2H, H-15,
H-17), 7.52 (d, J=7.3 Hz, 1H, H-16), 7.26 (d, J=8.7 Hz, 2H, H-8,
1
ieved with the aid of 2D NMR techniques (1H–1H COSY and H–
13C HSQC). For photostationary state (PSS) determination, all
1H NMR spectra were recorded in [D6]DMSO (cf. Table 2). NMR
assignments are in accordance with the compound numbering
indicated in Figure 4. The glycoside glycone moiety is num-
bered from 1–6, aglycone numbering is ascending from 7,
starting with the atom adjacent to the glycosidic bond. UV/Vis
absorption spectra were performed on Perkin-Elmer Lambda-
14 and Varian Cary-5000 at 18ꢂ18C. Irradiation (E!Z isomeri-
zation) was carried out with a high-pressure mercury lamp UV-
P 250C from Panacol-Elosol (Steinbach, Germany). The band-
H-12), 5.53 (bs, 1H, H-1), 3.89 (dd~bs, 1H, H-2), 3.73 (dd, J3,4
=
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9.2 Hz, J3,2 =3.0 Hz, 1H, H-3), 3.58–3.47 (m, 3H, H-6a, H-4, H-
6b), 3.38 (mc, 1H, H-5); 13C NMR (125 MHz, [D6]DMSO): d=
158.9 (C-7), 155.5 (C-13), 151.9 (C-10), 130.9 (C-16), 129.4 (C-15,
C-17), 124.3 (C-9, C-11), 122.3 (C-14, C-18), 117.1 (C-8, C-12),
98.7 (C-1), 75.2 (C-5), 70.6 (C-3), 69.9 (C-2), 66.6 (C-4), 60.9 (C-6);
IR (ATR): v˜ =3337, 2920, 1599, 1584, 1496, 1227 cmꢁ1; e=
25907ꢂ529 Lmolꢁ1 cmꢁ1; MS (MALDI-TOF): m/z [M+H]+ calcd
for C18H20N2O6: 361.36, found: 361.21; HRMS: m/z [M+H]+
calcd for C18H20N2O6: 361.1394, found: 361.1388; Anal. calcd for
C18H20N2O6 ꢃ0.1H2O (360.13): C 59.99, H 5.59, N 7.77, found: C
59.69, H 5.62, N 7.74.
696 Lmolꢁ1 cmꢁ1; MS (MALDI-TOF): m/z [M+Na]+ calcd for
C20H22N2O8: 441.14, found: 441.08; HRMS: m/z [M+H]+ calcd
for C20H22N2O8: 419.1376, found: 419.1372; Anal. calcd for
C20H22N2O8 (418.13): C 57.41, H 5.30, N 6.70, found: C 57.27, H
5.48, N 6.68.
E-p-(Phenylazo)phenyl b-d-glucopyranoside (4): The protect-
ed glycoside 14 (300 mg, 0.568 mmol) was dissolved in dry
MeOH (3 mL) and treated with NaOMe (6 mg), under N2 atmos-
phere. The reaction mixture was stirred at RT overnight, then it
was neutralized with Amberlite IR 120 ion exchange resin, fil-
tered and the filtrate evaporated under reduced pressure. The
crude product was purified by flash column chromatography
(10% MeOH in CH2Cl2) to yield unprotected glycoside 4 as
yellow solid (185 mg, 0.514 mmol, 90%): mp: 180–1818C; Rf =
0.29 (cyclohexane/MeOH, 4:1); [a]2D0 =ꢁ0.37 (c=0.85, DMSO);
1H NMR (500 MHz, [D6]DMSO): d=7.90 (d, J=8.8 Hz, 2H, H-9,
H-11), 7.87 (d, J=7.4 Hz, 2H, H-14, H-18), 7.61–7.58 (m, 2H, H-
15, H-17), 7.54 (mc, 1H, H-16), 7.23 (d, J=8.9 Hz, 2H, H-8, H-
E-p-(o-Carboxyphenylazo)phenyl a-d-mannopyranoside (2):
LiOH (14.8 mg, 0.622 mmol) was added to a solution of methyl
ester 3 (200 mg, 0.478 mmol) in THF/H2O (2:1, 3 mL), and the
reaction mixture was stirred overnight at RT. It was neutralized
with Amberlite IR 120 ion exchange resin, diluted with MeOH
(25 mL), and filtered. The filtrate was evaporated under re-
duced pressure to get pure glycoside 2 as a pale yellow solid
(180 mg, 0.45 mmol, 93%): mp: 116–1178C; Rf =0.21 (EtOAc/
12), 5.04 (d, J=7.3 Hz, 1H, H-1), 3.73 (dd, J6a,6b =11.6, J5,6a
=
1
MeOH, 8:2); [a]2D0 = +1.21 (c=0.9, DMSO); H NMR (500 MHz,
5.2 Hz, 1H, H-6a), 3.51 (dd~t, J5,6a =5.9 Hz, J6a,6b =11.8, 1H, H-
6b), 3.42 (ddd, J5,6a =5.7, J5,6b =2.8 Hz, J4,5 =9.2 Hz 1H, H-5),
3.32–3.28 (m, 2H, H-3, H-2), 3.23–3.19 (m, 1H, H-4); 13C NMR
(125 MHz, [D6]DMSO): d=159.9 (C-7), 151.9 (C-13), 146.9 (C-10),
130.9 (C-16), 129.4 (C-15, C-17), 124.3 (C-9, C-11), 122.3 (C-14,
18), 116.7 (C-8, C-12), 100.0 (C-1), 77.1 (C-5), 76.5 (C-3), 73.2 (C-
2), 69.6 (C-4), 60.6 (C-6); IR (ATR): v˜ =3242, 1600, 1589, 1495,
CD3OD): d=7.94 (d, J=9.0 Hz, 2H, H-9, H-11), 7.92 (dd, J=7.7,
1.3 Hz, 1H, H-15), 7.73 (dd, J=8.1, 1.1 Hz, H-18), 7.68 (dt, J=
7.7, 1.5, 7.3 Hz, 1H, H-17), 7.59 (dt, J=7.5, 7.4, 1.3 Hz, 1H, H-
16), 7.34 (d, J=9.0 Hz, 2H, H-8, H-12), 5.65 (d, J=1.8 Hz, 1H, H-
1), 4.08 (dd, J2,3 =3.4, J2,1 =1.9 Hz, 1H, H-2), 3.96 (dd, J3,4 =9.5,
J
3,2 =3.4 Hz, 1H, H-3), 3.83–3.74 (m, 3H, H-4, H-6a, H-6b), 3.61
(ddd, 5,4 =9.8, 5,6a =5.4 Hz,
J
J
J
5,6b =2.5, 1H, H-5); 13C NMR
1232 cmꢁ1; e=23274ꢂ1121 Lmolꢁ1 cmꢁ1
; MS (MALDI-TOF):
(125 MHz, CD3OD): d=170.9 (C-19), 161.0 (C-7), 152.5 (C-13),
149.1 (C-10), 133.1 (C-17), 131.2 (C-16), 130.9 (C-15), 126.8 (C-
14), 126.2 (C-9, C-11), 118.6 (C-18), 118.1 (C-8, C-12), 100.1 (C-1),
75.8 (C-5), 72.4 (C-3), 71.8 (C-2), 68.3 (C-4), 62.7 (C-6); IR (ATR):
v˜ =3394, 2936, 1719, 1595, 1498, 1243 cmꢁ1; e=29362ꢂ
1037 Lmolꢁ1 cmꢁ1; MS (MALDI-TOF): m/z [M+Na]+ calcd for
C19H20N2O8: 427.37, found: 427.10; HRMS: m/z [M+H]+ calcd
for C19H20N2O8: 405.1292, found: 405.1282.
m/z [M+H]+ calcd for C18H20N2O6: 361.36, found: 361.17;
HRMS: m/z [M+H]+ calcd for C18H20N2O6: 361.1394, found:
361.1385; Anal. calcd for C18H20N2O6 (360.13): C 59.99, H 5.59, N
7.77, found: C 59.55, H 5.59, N 7.13.
E-4-(2’-Carboxyphenylazo)phenyl
b-d-glucopyranoside (5):
Methyl ester 6 (100 mg, 0.24 mmol) was dissolved in THF/H2O
(2:1, 3 mL), LiOH (7.5 mg, 0.31 mmol) was added, and the reac-
tion mixture stirred at RT overnight. The reaction mixture was
neutralized with Amberlite IR 120 ion exchange resin, diluted
with MeOH (20 mL) and filtered. The filtrate was evaporated
under reduced pressure to yield glycoside 5 as a pale yellow
solid (88 mg, 0.22 mmol, 91%): mp: 194–1958C; Rf =0.22
(EtOAc/MeOH, 8:2); [a]2D0 =ꢁ0.39 (c=0.78, DMSO); 1H NMR
(500 MHz, CD3OD): d=7.94 (d, J=9.0 Hz, 2H, H-9, H-11), 7.82
(dd, J=7.6, 1.3 Hz, 1H, H-15), 7.71 (dd, J=7.8 H, 0.9 Hz, 1H, H-
18), 7.60 (dt, J=8.0, 7.7, 1.5 Hz, 1H, H-17), 7.54 (dt, J=7.4, 7.4,
1.3, 1H, H-16), 7.28 (d, J=9.0 Hz, 2H, H-8, H-12), 5.07 (d, J=
7.6 Hz, 1H, H-1), 3.95 (dd, J6a,6b =12.1, J5,6a =2.2 Hz, 1H, H-6a),
3.75 (dd, J6a,6b =12.1, J5,6b =5.7 Hz, 1H, H-6b), 3.56–3.52 (m, 3H,
H-2, H-3, H-5), 3.45 (mc, 1H, H-4); 13C NMR (125 MHz, CD3OD,
125 MHz): d=173.3 (C-19), 161.9 (C-7), 151.8 (C-13), 149.3 (C-
10), 134.2 (C-14), 132.0 (C-17), 131.2 (C-16), 130.2 (C-15), 126.0
(C-9, C-11), 118.4 (C-18), 117.9 (C-8, C-12), 101.9 (C-1), 78.3 (C-5),
77.9 (C-3), 74.7 (C-2), 71.3 (C-4), 62.5 (C-6); IR (ATR): v˜ =3329,
E-p-(o-Methoxycarbonylphenylazo)phenyl a-d-mannopyra-
noside (3): A catalytic amount of NaOMe was added under N2
atmosphere to a solution of the acetylated mannoside 17
(2.00 g, 3.41 mmol) in dry MeOH (20 mL). The reaction mixture
was stirred at RT overnight, neutralized with Amberlite IR 120
ion exchange resin and filtered. The filtrate was concentrated
under reduced pressure. Purification by flash column chroma-
tography (EtOAc/MeOH, 9:1) gave 3 as an orange solid (1.20 g,
2.87 mmol, 89%): mp: 108–1108C; Rf =0.29 (EtOAc/MeOH, 9:1);
1
[a]2D0 = +1.34 (c=1.0, MeOH); H NMR (500 MHz, D2O): d=7.85
(d, J=8.4 Hz, H-15), 7.84(d, J=9.0 Hz, 2H, H-9, H-11), 7.65 (t, J=
7.6 Hz, 1H, H-17), 7.53 (t, J=7.9 Hz, H-16), 7.47 (d, J=7.7 Hz,
1H, H-18), 7.24 (d, J=8.8 Hz, 2H, H-8, H-12), 5.67 (d, 1H, J1,2
1.2 Hz H-1), 4.14 (dd, J1,2 =1.6, J1,3 =3.2 Hz,1H, H-2), 4.02 (dd,
3,4 =9.6, J2,3 =3.3 Hz, 1H, H-3), 3.83 (s, 3H, CO2CH3), 3.75–3.66
=
J
(m, 3H, H-4, H-6a,H-6b), 3.64–3.30 (m, 1H, H-5); 13C NMR
(125 MHz, D2O): d=170.1 (C-19), 169.8 (C-7), 158.7 (C-13), 147.2
(C-10), 133.1 (C-17), 130.1 (C-15), 129.9 (C-16), 126.0 (C-14),
124.8 (C-9/C-11), 119.8 (C-18), 117.3 (C-8/C-12), 97.8 (C-1), 73.5
(C-5), 70.3 (C-3), 69.7 (C-2), 66.5 (C-4), 60.6 (C-6), 53.0 (C-20); IR
(ATR): v˜ =3344, 2930, 1715, 1596, 1497, 1231 cmꢁ1; e=21694ꢂ
2498,
1699,
1592,
1499,
1246 cmꢁ1
;
e=28335ꢂ
345 Lmolꢁ1 cmꢁ1; MS (MALDI-TOF): m/z [M+Na]+ calcd for
C19H20N2O8: 427.37, found: 427.14; HRMS: m/z [M+H]+ calcd
for C19H20N2O8: 405.1292, found: 405.1283.
ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1
E-p-(o-Methoxycarbonylphenylazo)phenyl b-d-glucopyrano-
side (6): Protected glucoside 18 (152 mg, 0.259 mmol) was dis-
solved in dry MeOH (2 mL), and a catalytic amount of NaOMe
was added under N2 atmosphere. The reaction mixture was
stirred at RT overnight, neutralized with Amberlite IR 120 ion
exhange resin and filtered. The filtrate was evaporated under
reduced pressure, and the crude product was purified by flash
chromatography (EtOAc/MeOH, 9:1) to yield 6 as a pale yellow
solid (90 mg, 215 mmol, 83%): mp: 142–1438C; Rf =0.29
(EtOAc/MeOH, 4:1); [a]2D0 =ꢁ0.66 (c=1.0, MeOH); 1H NMR
(500 MHz, CD3OD): d=7.88 (d, J=9.0 Hz, 2H, H-9, H-11), 7.76
(d, J=7.4 Hz, 1H, H-15), 7.67-7.64 (m, 2H, H-17, H-18), 7.53 (mc,
1H, H-16), 7.26 (d, J=9.0 Hz, 2H, H-8, H-12), 5.05 (d, J=7.6 Hz,
1H, H-1), 3.93 (dd, J6a,6b =12.1, J5,6a =2.3 Hz, 1H, H-6a), 3.87 (s,
3H, CO2CH3), 3.72 (dd, J6a,6b =12.1, J5,6b =5.7 Hz, 1H, H-6b),
3.54–3.48 (m, 3H, H-2, H-3, H-5), 3.42 (mc, 1H, H-4); 13C NMR
(125 MHz, CD3OD): d=169.9 (C-19), 161.9 (C-7), 152.9 (C-13),
149.2 (C-10), 133.0 (C-17), 130.8 (C-16), 130.5 (C-15), 130.0 (C-
14), 125.9 (C-9, C-11), 120.3 (C-18), 118.0 (C-8, C-12), 101.9 (C-1),
78.3 (C-5), 77.9 (C-3), 74.8 (C-2), 71.3 (C-4), 62.5 (C-6), 52.9 (C-
20); IR (ATR): v˜ =3323, 2942, 1723, 1598, 1498, 1235 cmꢁ1; e=
MeOH, 1:1); [a]2D0 = +1.93 (c=0.18, DMSO); H NMR (500 MHz,
[D6]DMSO): d=7.84 (d, J=9.0 Hz, 2H, H-9, H-11), 7.77 (mc, 1H,
H-15), 7.66 (mc, 1H, H-17), 7.56 (mc, 2H, H-16, H-18), 7.29 (d,
J=9.0 Hz, 2H, H-8, H-12), 5.57 (d, J1,2 =3.6 Hz, 1H, H-1), 3.66
(dd~t, J3,4 =9.2 Hz, 1H, H-3), 3.57 (mc, 1H, H-6a), 3.48 (mc, 1H,
H-6b), 3.45 (mc, 1H, H-5), 3.43 (dd, J2,3 =9.7, J1,2 =3.6 Hz, 1H, H-
2), 3.21 (dd~t, J4,3 =9.2 Hz, 1H, H-4); 13C NMR (125 MHz,
[D6]DMSO): d=168.3 (C-19), 159.9 (C-7), 150.7 (C-13), 146.9 (C-
10), 131.6 (C-17), 130.0 (C-14), 129.9 (C-16), 129.1 (C-15), 124.6
(C-9, C-11), 118.1 (C-18), 117.2 (C-8, C-12), 97.6 (C-1), 74.0 (C-5),
72.8 (C-3), 71.3 (C-2), 69.7 (C-4), 60.6 (C-6); IR (ATR): v˜ =3366,
2921,
1728,
1597,
1479,
1240 cmꢁ1
;
e=13715ꢂ
2132 Lmolꢁ1 cmꢁ1; MS (MALDI-TOF): m/z [M+Na]+ calcd for
C19H20N2O8: 427.11, found: 427.10; HRMS: m/z [M+H]+ calcd
for C19H20N2O8: 405.1292, found: 405.1276.
E-p-(o-Methoxycarbonylphenylazo)phenyl a-d-glucopyrano-
side (9): NaOMe (18 mg) was added under N2 atmosphere to
a solution of glycoside 22 (630 mg, 1.07 mmol) in dry MeOH
(12 mL), and the reaction mixture was stirred at RT for 18 h. It
was neutralized with Amberlite IR 120 ion exchange resin and
filtered, and the filtrate concentrated under reduced pressure.
The residual was purified by GPC on Sephadex LH-20 (MeOH)
to yield 9 as an orange solid (431 mg, 1.03 mmol, 96%): mp:
144–1458C; Rf =0.72 (EtOAc/MeOH, 1:1); [a]2D0 = +1.81 (c=0.2,
DMSO); 1H NMR (500 MHz, [D6]DMSO): d=7.84 (d, J=8.9 Hz,
2H, H-9, H-11), 7.76 (dd, J=7.6, 1.4 Hz, 1H, H-15), 7.70 (mc, 1H,
H-17), 7.63 (dd, J=8.0, 1.2 Hz, 1H, H-18), 7.58 (dt, J=7.4,
1.3 Hz, 1H, H-16) 7.29 (d, J=9.0 Hz, 2H, H-8, H-12), 5.55 (d,
18722ꢂ400 Lmolꢁ1 cmꢁ1
;
MS (MALDI-TOF): m/z [M+Na]+
calcd for C20H22N2O8: 441.14, found: 441.12; HRMS: m/z [M+
H]+ calcd for C20H22N2O8: 419.1376, found: 419.1362; Anal.
calcd for C20H22N2O8 ꢃ1.4 H2O (418.14): C 55.96, H 5.45, N 6.53,
found: C 56.06, H 5.52, N 6.34.
E-p-(Phenylazo)phenyl a-d-glucopyranoside (7): Glucoside 19
(238 mg, 0.89 mmol) and nitrosobenzene (103 mg, 0.97 mmol,
1.1 equiv) were dissolved in glacial acid (20 mL), and the reac-
tion mixture was stirred at RT for 18 h. After it was concentrat-
ed under reduced pressure, the residual was purified by flash
column chromatography (EtOAc/MeOH, 9:1!MeOH) to obtain
glucoside 7 as an orange solid (305 mg, 0.85 mmol, 96%): mp:
206–2078C; Rf =0.62 (EtOAc/MeOH, 1:1); [a]2D0 = +2.21 (c=0.2,
DMSO); 1H NMR (500 MHz, [D6]DMSO): d=7.88 (d, J=8.9 Hz,
2H, H-9, H-11), 7.84 (d, J=7.2 Hz, 2H, H-14, H-18), 7.58 (t, J=
7.4 Hz, 2H, H-15, H-17), 7.52 (d, J=7.2 Hz, 1H, H-16), 7.28 (d,
J=8.9 Hz, 2H, H-8, H-12), 5.55 (d, J1,2 =3.6 Hz, 1H, H-1), 3.66
(dd~t, J=9.2 Hz, 1H, H-3), 3.56 (mc, 1H, H-6a), 3.47 (mc, 1H, H-
6b), 3.44 (mc, 1H, H-5), 3.42 (dd, J2,3 =9.7, J2,1 =3.6 Hz, 1H, H-2),
3.21 (dd~t, J=9.1 Hz, 1H, H-4); 13C NMR (125 MHz, [D6]DMSO):
d=158.9 (C-7), 155.5 (C-13), 151.9 (C-10), 130.9 (C-16), 129.4
(C-15, C-17), 124.3 (C-9, C-11), 122.3 (C-14, C-18), 117.2 (C-8, C-
12), 97.6 (C-1), 73.9 (C-5), 72.8 (C-3), 71.3 (C-2), 69.6 (C-4), 60.5
J
1,2 =3.6 Hz, 1H, H-1), 3.81 (s, 3H, CO2CH3), 3.66 (dd~t, J3,4
9.2 Hz, 1H, H-3), 3.57 (dd, J5,6a =11.4, J6a,6b =1.6 Hz, 1H, H-6a),
3.48 (mc, 1H, H-6b), 3.46 (mc, 1H, H-5), 3.43 (dd, J2,3 =9.7, J2,1
=
=
3.5 Hz, 1H, H-2), 3.21 (dd~t, J4,3 =9.2 Hz, 1H, H-4); 13C NMR
(150 MHz, [D6]DMSO): d=167.6 (C-19), 160.22 (C-7), 150.8 (C-
13), 146.9 (C-10), 132.2 (C-17), 130.1 (C-16), 129.3 (C-15), 128.4
(C-14), 124.7 (C-9, C-11), 119.5 (C-18), 117.4 (C-8, C-12), 97.7 (C-
1), 74.1 (C-5), 72.9 (C-3), 71.4 (C-2), 69.8 (C-4), 60.6 (C-6), 52.4
(C-20); IR (ATR): v˜ =3327, 2921, 2853, 1715, 1596, 1497,
1230 cmꢁ1; e=16943ꢂ383 Lmolꢁ1 cmꢁ1; MS (ESI): m/z [M+K]+
calcd for C20H22N2O8: 457.14, found: 457.11; HRMS: m/z [M+
H]+ calcd for C20H22N2O8: 419.1449, found: 419.1439.
E-p-(Phenylazo)phenyl 2,3,4,6-tetra-O-acetyl-a-d-mannopyra-
noside (13): BF3·Et2O (347 mL, 2.74 mmol, 1.2 equiv) was added
at 08C under N2 atmosphere to a solution of mannosyl donor
10 (900 mg, 1.83 mmol) and p-hydroxyazobenzene (12,
398 mg, 2.01 mmol) in dry CH2Cl2 (18 mL). The reaction mixture
was stirred at RT overnight, and quenched by addition of satu-
rated aq NaHCO3 (18 mL). The phases were separated, and the
aqueous phase was extracted with CH2Cl2 (3ꢃ30 mL). The
combined organic phases were washed with H2O (2ꢃ20 mL),
dried over Na2SO4, filtered and concentrated under reduced
pressure. Purification of the crude product by column chroma-
tography (cyclohexane/EtOAc, 3:7) gave glycoside 13 as an
orange crystalline solid (780 mg, 1.47 mmol, 81%): mp: 53–
558C; Rf =0.25 (cyclohexane/EtOAc, 7:3); [a]2D0 = +0.86 (c=0.9,
(C-6); IR (ATR): v˜ =3382, 3288, 2918, 1597, 1496, 1234; cmꢁ1
;
e=15804ꢂ256 Lmolꢁ1 cmꢁ1; MS (ESI): m/z [M+Na]+ calcd for
C18H20N2O6: 383.121, found: 383.138; HRMS: m/z [M+H]+
calcd for C18H20N2O6: 361.1394, found: 361.1379.
E-p-(o-Carboxyphenylazo)phenyl
a-d-glucopyranoside (8):
Methyl ester 9 (430 mg, 1.03 mmol) was dissolved in THF/H2O
(1:1, 10 mL), LiOH (49 mg, 2.06 mmol, 2 equiv) was added, and
the reaction mixture was stirred overnight at RT. After neutrali-
zation with Amberlite IR 120 ion exchange resin, the reaction
mixture was filtered, and the filtrate concentrated under re-
duced pressure to obtain pure glycoside 8 as a yellow solid
(395 mg, 0.78 mmol, 95%): mp: 173–1748C; Rf =0.36 (EtOAc/
1
DMSO); H NMR (500 MHz, CDCl3): d=7.92 (d, J=9.1 Hz, 2H, H-
9, H-11), 7.90–7.87 (m, 2H, H-14, H-18), 7.52–7.49 (m, 2H, H-15,
ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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H-17), 7.46 (dt, J=4.9, 1.9 Hz, 1H, H-16), 7.23 (d, J=9.1 Hz, 2H,
H-8, H-12), 5.62 (d, J1,2 =1.8 Hz, 1H, H-1), 5.39 (dd, J3,4 =10.0,
H-17, H-18), 7.49–7.46 (m, 1H, H-16), 7.23 (d, J=8.9 Hz, 2H, H-
8, H-12), 5.63 (d, J1,2 =1.7 Hz, 1H, H-1), 5.58 (dd, J3,4 =10.0, J3,2
3.5 Hz, 1H, H-3), 5.48 (dd, J2,3 =3.5 Hz, J1,2 =1.8 Hz, 1H, H-2),
5.39 (t, J4,3 =J4,5 =9.9 Hz, 1H, H-4), 4.30 (dd, J6a,6b =12.7, J5,6a
=
J2,3 =3.6 Hz, 1H, H-3), 5.49 (dd, J2,3 =3.5 Hz, J1,2 =1.8 Hz, 1H, H-
2), 5.39 (dd~t, J4,3 =J4,5 =10.1 Hz, 1H, H-4), 4.28 (mc, 1H, H-6a),
4.12–4.07 (m, 2H, H-5, H-6b), 2.21, 2.06, 2.05, 2.03 (each s, each
3H, 4OAc); 13C NMR (125 MHz, CDCl3): d=170.5, 169.9, 169.9,
169.7 (4 C=O), 157.6 (C-7), 152.6 (C-13), 148.4 (C-10), 130.8 (C-
16), 128.9 (C-15, C-17), 124.6 (C-9, C-11), 123.1 (C-14, 18), 116.8
(C-8, C-12), 95.7 (C-1), 69.4 (C-5), 69.3 (C-2), 68.8 (C-3), 65.9 (C-
4), 62.1 (C-6), 20.9, 20.7, 20.7, 20.6 (4CO2CH3); IR (ATR): v˜ =
2929, 1743, 1598, 1496, 1366, 1209, 1029 cmꢁ1; MS (ESI): m/z
[M+Na]+ calcd for C26H28N2O10: 551.57, found: 551.17.
=
5.9 Hz, 1H, H-6a), 4.08–4.11 (m, 2H, H-5, H-6b), 3.91 (s, 3H,
CO2CH3), 2.22, 2.06, 2.05, 2.03 (each s, each 3H, 4OAc);
13C NMR (125 MHz, CDCl3): d=170.4, 169.9, 169.9, 169.7 (4C=
O), 167.9 (C-19), 157.9 (C-7), 151.9 (C-13), 148.4 (C-10), 131.9 (C-
17), 129.7 (C-15), 129.6 (C-16), 128.5 (C-14), 125.0 (C-9, C-11),
118.8 (C-18), 116.8 (C-8, C-12), 95.6 (C-1), 69.5 (C-5), 69.2 (C-3),
68.7 (C-2), 65.8 (C-4), 62.0 (C-6), 52.3 (C-20), 20.9, 20.7, 20.7,
20.6 (4CO2CH3); IR (ATR): v˜ =2954, 1744, 1715, 1597, 1498,
1366, 1210 cmꢁ1; MS (ESI): m/z [M+Na]+ calcd for C28H30N2O12:
609.58, found: 609.16.
E-p-(Phenylazo)phenyl 2,3,4,6-tetra-O-acetyl-b-d-glucopyra-
noside (14): Glucosyl donor 11 (500 mg, 1.02 mmol) and p-hy-
droxyazobenzene (12, 221 mg, 1.12 mmol) were dissolved in
dry CH2Cl2 (10 mL), and BF3·Et2O (128 mL, 1.02 mmol) was
added at 08C. The reaction mixture was stirred at RT overnight,
and the reaction was quenched by addition of saturated aq
NaHCO3 (1 mL). The phases were separated, and the aqueous
phase was extracted with CH2Cl2 (25 mL). The combined organ-
ic phases were washed with H2O (2ꢃ10 mL), dried over
Na2SO4, filtered and concentrated under reduced pressure. The
residual was purified by flash chromatography (cyclohexane/
EtOAc, 3:7) to yield glucoside 14 as an orange solid (390 mg,
0.74 mmol, 73%): mp: 166–1678C; Rf =0.27 (cyclohexane/
EtOAc, 7:3); 1H NMR (500 MHz, CDCl3): d=7.91 (d, J=9.0 Hz,
2H, H-9, H-11), 7.89 (d, J=7.2 Hz, 2H, H-14, H-18), 7.53–7.49
(m, 2H, H-15, H-17), 7.46 (mc, 1H, H-16), 7.11 (d, J=8.9 Hz, 2H,
H-8, H-12), 5.33–5.31 (m, 2H, H-2, H-3), 5.21–5.27 (m, 2H, H-1,
H-4), 4.31 (dd, J6a,6b =12.3, J5,6a =5.5 Hz, 1H, H-6a), 4.20 (dd,
E-p-(o-Methoxycarbonylphenylazo)phenyl
2,3,4,6-tetra-O-
acetyl-b-d-glucopyranoside (18): Glucosyl donor 11 (170 mg,
0.345 mmol) and o-(p-hydroxyphenylazo)methyl benzoate (16,
97.3 mg, 0.38 mmol) were dissolved in dry CH2Cl2 (5 mL), and
BF3·Et2O (53 mL, 0.42 mmol, 1.2 equiv) was added at 08C. The
reaction mixture was stirred at RT overnight, and the reaction
was quenched with saturated aq NaHCO3 (10 mL). The phases
were separated, and the aqueous phase was extracted with
CH2Cl2 (20 mL). The combined organic phases were washed
with H2O (10 mL), dried over Na2SO4, filtered and concentrated
under reduced pressure. Purification of the residual by column
chromatography (cyclohexane/EtOAc, 7:3) gave glucoside 18
as an orange solid (160 mg, 0.273 mmol, 79%): mp: 118–
1198C; Rf =0.24 (cyclohexane/EtOAc, 7:3); [a]2D0 =ꢁ0.20 (c=1.0,
1
MeOH); H NMR (500 MHz, CD3OD): d=7.89 (d, J=9.0 Hz, 2H,
H-9, H-11), 7.77 (td, J=7.6, 1.0 Hz, 1H, H-15), 7.65–7.64 (m, 2H,
H-17, H-18), 7.54 (mc, 1H, H-16), 7.19 (d, J=9.1 Hz, 2H, H-8, H-
12), 5.49 (d, J1,2 =7.9 Hz, 1H, H-1), 5.42 (dd~t, J3,4 =J2,3 =9.5 Hz,
1H, H-3), 5.22 (dd, J2,3 =9.6 Hz, J1,2 =7.9 Hz, 1H, H-2), 5.14 (dd~
t, J4,3 =J4,5 =9.7 Hz, 1H, H-4), 4.33 (dd, J6a,6b =12.3, J5,6a =5.1 Hz,
1H, H-6a), 4.19 (dd, J6a,6b =12.3 Hz, J5,6b5 =2.4 Hz, 1H, H-6b),
3.87 (s, 3H, CO2CH3), 2.06, 2.06, 2.04, 2.01 (each s, each 3H,
4OAc); 13C NMR (125 MHz, CD3OD): d=172.2, 171.5, 171.2,
171.1 (4C=O), 169.8 (C-19), 160.8 (C-7), 152.9 (C-13), 149.7 (C-
10), 133.1 (C-17), 130.9 (C-16), 130.5 (C-15), 130.1 (C-14), 125.9
(C-9, C-11), 120.2 (C-18), 118.1 (C-9, C-12), 99.1 (C-1), 74.3 (C-3),
73.2 (C-5), 72.6 (C-2), 69.7 (C-4), 63.1 (C-6), 52.9 (C-20), 20.6,
20.5, 20.5, 20.5 (4CO2CH3); IR (ATR): v˜ =1739, 1598, 1501, 1367,
1211 cmꢁ1; MS (ESI): m/z [M+Na]+ calcd for C28H30N2O12:
609.58, found: 609.17.
J6a,6b =12.3, J5,6b =2.4 Hz, 1H, H-6a), 3.92 (ddd, J5,6a =5.5, J5,6b =
2.4 Hz, J4,5 =9.9 Hz 1H, H-5), 2.09, 2.08, 2.06, 2.05 (each s, each
3H, 4OAc); 13C NMR (125 MHz, CDCl3): d=170.6, 170.2, 169.4,
169.3 (4C=O), 158.8 (C-7), 152.6 (C-13), 148.6 (C-10), 130.8 (C-
16), 129.1 (C-15, C-17), 124.5 (C-9, C-11), 122.7 (C-14, C-18),
117.1 (C-8, C-12), 98.7 (C-1), 72.6 (C-5), 72.3 (C-2), 71.2 (C-3),
68.3 (C-4), 61.9 (C-6), 20.7, 20.7, 20.6, 20.6 (4CO2CH3); IR (ATR):
v˜ =1740, 1598, 1497, 1366, 1220 cmꢁ1; MS (ESI): m/z [M+Na]+
calcd for C26H28N2O10: 551.51, found: 551.17.
E-p-(o-Methoxycarbonylphenylazo)phenyl
acetyl-a-d-mannopyranoside (17):
2,3,4,6-tetra-O-
(927 mL,
BF3·Et2O
7.32 mmol, 1.2 equiv) was added at 08C under N2 atmosphere
to a solution of mannosyl donor 10 (3.00 g, 6.09 mmol) and
p-(o-methoxycarbonylphenylazo)phenol (16, 1.72 g, 6.72 mmol)
in dry CH2Cl2 (45 mL). The reaction mixture was stirred at RT
overnight, and the reaction was quenched by addition of satu-
rated aq NaHCO3 (30 mL). The phases were separated and the
aqueous phase was extracted with CH2Cl2 (3ꢃ100 mL). The
combined organic layers were washed with H2O (2ꢃ50 mL),
dried over Na2SO4, filtered and concentrated under reduced
pressure. Purification of the residual by flash column chroma-
tography (cyclohexane/EtOAc, 1:4) gave glycoside 17 as
a yellow crystalline solid (3.00 g, 5.12 mmol, 84%): mp: 120–
1218C; Rf =0.21 (cyclohexane/EtOAc, 1:4), [a]2D0 = +0.806 (c=
1.0, MeOH); 1H NMR (500 MHz, CDCl3): d=7.91 (d, J=8.9 Hz,
2H, H-9, H-11), 7.82 (d, J=7.5 Hz, 1H, H-15), 7.61-7.56 (m, 2H,
E-p-(o-Methoxycarbonylphenylazo)phenyl
acetyl-a-d-glucopyranoside (22): Aniline
2,3,4,6-tetra-O-
20 (966 mg,
6.39 mmol) and CH2Cl2 (20 mL) were added to a solution of
oxone (7.86 g, 12.8 mmol) in H2O (20 mL), and the reaction
mixture was stirred at RT for 20 h under N2 atmosphere. The
phases were separated, and the aqueous phase was extracted
with CH2Cl2 (50 mL). The combined organic phases were suc-
cessively washed with aq HCl (1m, 50 mL), saturated aq
NaHCO3 (50 mL) and brine (50 mL), dried over MgSO4, filtered
and concentrated to yield the crude nitroso intermediate 21
(1.05 g, 6.36 mmol), which was processed without further pu-
rification. It was added to the amino-functionalized mannoside
ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemistryOpen 2014, 3, 99 – 108 106

www.chemistryopen.org
19[14] (648 mg, 2.39 mmol), dissolved in glacial acid (20 mL) and
stirred for 18 h at RT. The solution was concentrated, and the
crude product dissolved in pyridine (5 mL) and treated with
Ac2O (1.13 mL, 11.9 mmol, 5 equiv) at RT for 52 h under N2 at-
mosphere. The solution was concentrated and co-evaporated
with toluene. The residual was purified by flash column chro-
matography (EtOAc/cyclohexane, pure EtOAc!1:1) to yield
protected glycoside 22 as an orange solid (1.25 g, 2.13 mmol,
89%): mp: 558C; Rf =0.5 (MeOH/EtOAc, 1:2); [a]2D0 = +1.83 (c=
1211 cmꢁ1; MS (ESI): m/z [M+Na]+ calcd for C26H28N2O11:
567.51, found: 567.16.
28: mp: 167–1698C; Rf =0.15 (cyclohexane/EtOAc, 1:1); [a]2D0 =
1
+0.89 (c=1.0, CH2Cl2); H NMR (500 MHz, CDCl3): d=7.89 (dd,
J=9.0 Hz, 4H, H-9, H-11, H-14, H-18), 7.22 (d, J=9.0 Hz, 4H, H-
8, H-12, H-15, H-17), 5.61 (d, J1,2 =1.7 Hz, 2H, 2 H-1), 5.58 (dd,
J3,4 =10.0, J2,3 =3.5 Hz, 2H, 2 H-3), 5.48 (dd, J2,3 =3.5 Hz, J1,2 =
1.8 Hz, 2H, 2 H-2), 5.38 (dd~t, J3,4 =J4,5 =10.1 Hz, 2H, 2 H-4),
4.31–4.26 (m, 2H, 2 H-6a), 4.11-4.07 (m, 4H, 2 H-5, 2 H-6b),
2.21, 2.06, 2.05, 2.03 (each s, each 6H, 8OAc); 13C NMR
(150 MHz, CDCl3): d=170.5, 169.9, 169.9, 169.7 (8 C=O), 157.5
(C-7, C-16), 148.4 (C-13, C-10), 124.5 (C-9, C-11, C-14, C-18),
116.8 (C-8, C-12, C-15, C-17), 95.7 (C-1), 69.5 (C-5), 69.3 (C-2),
68.8 (C-3), 65.9 (C-4), 62.1 (C-6), 20.9, 20.7, 20.7, 20.7
(8CO2CH3C); IR (ATR): v˜ =2992, 1748, 1599, 1582, 1496, 1368,
1213 cmꢁ1; MS (ESI): m/z [M+Na]+ calcd for C40H46N2O20:
897.26, found: 897.23.
1
0.26, DMSO);); H NMR (500 MHz, CDCl3): d=7.91 (d, J=8.9 Hz,
2H, H-9, H-11), 7.81 (mc, 1H, H-15), 7.58 (mc, 2H, H-17, H-18),
7.47 (ddd, J=7.7, 6.4, 2.2 Hz, 1H, H-16), 7.22 (d, J=8.9 Hz, 2H,
H-8, H-12), 5.83 (d, J1,2 =3.6 Hz, 1H, H-1), 5.72 (dd, J2,3 =10.0,
J
3,4 =9.6 Hz, 1H, H-3), 5.18 (dd, J3,4 =9.5 Hz, J4,5 =10.1 Hz, 1H,
H-4), 5.08 (dd, J1,2 =3.6 Hz, J2,3 =10.2 1H, H-2), 4.26 (dd, J5,6a
12.3, J6a,6b =4.52 Hz, 1H, H-6a), 4.11 (mc, 1H, H-5), 4.07 (dd,
5,6b =12.2, J6a,6b =2.3 Hz, 1H, H-6b), 3.91 (s, 3H, CO2CH3), 2.08,
=
J
2.06, 2.05, 2.04 (each s, each 3H, 4OAc); 13C NMR (125 MHz,
CDCl3): d=170.5, 170.2, 169.5, 167.9 (4 C=O), 158.9 (C-7), 151.9
(C-13), 148.5 (C-10), 131.9 (C-17), 129.7 (C-15). 129.6 (C-16),
125.1 (C-9, C-11), 118.8 (C-18), 116.8 (C-8, C-12), 94.7 (C-1), 70.3
(C-2), 69.9 (C-3), 68.3 (C-5), 68.2 (C-4), 61.5 (C-6), 52.3 (C-20),
20.7, 20.66, 20.63, 20.59 (4CO2CH3); IR (ATR): v˜ =1741, 1596,
1498, 1367, 1214 cmꢁ1; MS (ESI): m/z [M+Na]+ calcd for
C28H30N2O12: 609.169, found: 609.167.
E-p-(p-Hydroxyphenylazo)phenyl 2,3,4,6-tetra-O-acetyl-b-d-
glucopyranoside (25): BF3·Et2O (280 mL, 2.16 mmol) was added
at 08C under N2 atmosphere to a solution of the glucosyl
donor 11 (907 mg, 1.84 mmol) and p,p’-dihydroxyazoben-
zene[16] (23, 304 mg, 1.42 mmol) in dry THF (5 mL). The reaction
mixture was stirred at RT overnight, and saturated aq NaHCO3
(5 mL) was added to quench the reaction. The solution was ex-
tracted with CH2Cl2 (3ꢃ5 mL). The combined organic phases
were washed with H2O (2ꢃ5 mL), dried over MgSO4, filtered
and concentrated under reduced pressure. Purification by flash
column chromatography (cyclohexane/EtOAc, 1:1) gave the
monoglycosylated product 25 as a yellow solid (239 mg,
0.440 mmol, 31%): mp: 89–918C; Rf =0.46 (cyclohexane/EtOAc,
E-p-(o-Hydroxyphenylazo)phenyl 2,3,4,6-tetra-O-acetyl-a-d-
mannopyranoside (24) and E-p-[p-(2,3,4,6-tetra-O-acetyl-a-d-
mannopyranosyloxy)]phenylazophenyl
acetyl-a-d-mannopyranoside (28):
2,3,4,6-tetra-O-
BF3·Et2O (260 mL,
2.01 mmol) was added at 08C under N2 atmosphere to a solu-
tion of mannosyl donor 10 (1.00 g, 2.03 mmol) and p,p’-dihy-
droxyazobenzene[16] (23, 200 mg, 0.93 mmol) in dry CH3CN
(15 mL). The reaction mixture was stirred at RT overnight, and
saturated aq NaHCO3 (5 mL) was added to quench the reac-
tion. After dilution with EtOAc (100 mL), the phases were sepa-
rated. The organic phase was washed with H2O (2ꢃ15 mL),
dried over Na2SO4, filtered and concentrated under reduced
pressure. Purification by flash column chromatography (cyclo-
hexane/EtOAc, 6:4) gave the monoglycosylated product 24
(190 mg, 0.349 mmol, 37%) as the first fraction, followed by
the divalent glycoside 28 (268 mg, 0.307 mmol, 31%) as pale
yellow solids.
1
1:3) [a]2D0 =ꢁ1.27 (c=0.92, MeOH); H NMR (500 MHz, CDCl3):
d=7.77 (d, J=9.0 Hz, 2H, H-9, H-11), 7.75 (d, J=8.9 Hz, 2H, H-
14, H-18), 7.00 (d, J=9.0 Hz, 2H, H-8, H-12), 6.86 (d, J=8.9 Hz,
2H, H-15, H-17), 6.19 (s, br, 1H, OH), 5.25 (mz, 2H, H-2, H-3),
5.12 (t, J=9.8 Hz, 1H, H-4), 5.09 (d, J1,2 =7.2 Hz, 1H, H-1), 4.30
(dd, J=12.3, 5.3 Hz, 1H, 1H-6a), 4.13 (dd, J=2.5, 12.3, 1H, H-
6b), 3.84 (ddd, J=10, 5.4, 2.5 Hz, 1H, H-5), 2.02 (s, 3H, OAc-6),
2.01, (s, 3H, OAc-2), 1.99, (s, 3H, OAc-4), 1.98 (s, 3H, OAc-3);
13C NMR (150 MHz, CDCl3): d=170.8 (CO2CH3-6) 170.4 (CO2CH3-
4), 169.5 (CO2CH3-2), 169.5 (CO2CH3-4), 158.6 (C-16), 158.3 (C-7),
148.7 (C-10), 146.9 (C-13), 124.8 (C-14, C-18), 124.2 (C-9, C-11),
117.1 (C-8, C-12), 115.8 (C-15, C-17), 98.8 (C-1), 72.7 (C-2), 72.2
(C-5), 71.2 (C-3), 68.3 (C-4), 62.0 (C-6), 20.7, 20.6, 20.6, 20.5
(4CO2CH3); IR (ATR): v˜ =3367, 2940, 2874, 1743, 1586, 1366,
1211 cmꢁ1; MS (ESI): m/z [M+H]+ calcd for C26H28N2O11: 545.2,
found: 545.3.
24: mp: 109–1108C; Rf =0.26 (cyclohexane/EtOAc, 1:1); [a]2D0 =
1
+0.75 (c=1.0, CH2Cl2); H NMR (600 MHz, CDCl3): d=7.85 (d,
J=9.0 Hz, 2H, H-14, H-18), 7.83 (d, J=8.9 Hz, 2H, H-9, H-11),
7.19 (d, J=9.0 Hz, 2H, H-15, H-17), 6.94 (d, J=8.8 Hz, 2H, H-8,
H-12), 5.61 (d, J1,2 =1.6 Hz, 1H, H-1), 5.59 (dd, J3,4 =10.0, J3,2
=
3.4 Hz, 1H, H-3), 5.48 (dd, J2,3 =3.5 Hz, J1,2 =1.8 Hz, 1H, H-2),
5.39 (dd~t, J3,4 =J4,5 =10.1 Hz, 1H, H-4), 4.30 (dd, J5,6a =12.1,
E-p-(p-Hydroxyphenylazo)phenyl a-d-mannopyranoside (26):
Protected mannoside 24 (100 mg, 0.184 mmol) was dissolved
in dry MeOH (2 mL), and a catalytic amount of NaOMe was
added. The reaction mixture stirred at RT overnight and then
neutralized with Amberlite IR 120 ion exchange resin. After fil-
tration, the filtrate evaporated under reduced pressure to yield
pure 26 as a light orange solid (61 mg, 0.162 mmol, 88%): mp:
206–2078C; Rf =0.18 (CH2Cl2/MeOH, 9:1); [a]2D0 = +1.02 (c=1.0,
J6a,6b =5.3 Hz, 1H, H-6a), 4.12–4.08 (m, 2H, H-5, H-6b), 2.22,
2.07, 2.06, 2.04 (each s, each 3H, 4OAc); 13C NMR (150 MHz,
CD3OD): d=170.7, 170.3, 170.1, 169.8 (4C=O), 158.3 (C-7),
157.2 (C-16), 148.5 (C-13), 147.1 (C-10), 124.8 (C-14, C-18), 124.3
(C-9, C-11), 116.8 (C-15, C-17), 115.8 (C-8, C-12), 95.7 (C-1), 69.4
(C-5), 69.3 (C-2), 68.9 (C-3), 65.9 (C-4), 62.1 (C-6), 20.9, 20.7,
20.7, 20.7 (CO2CH3); IR (ATR): v˜ =3407, 1744, 1587, 1498, 1368;
1
MeOH); H NMR (500 MHz, CD3OD): d=7.82 (d, J=9.0 Hz, 2H,
ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemistryOpen 2014, 3, 99 – 108 107

www.chemistryopen.org
H-9, H-11), 7.78 (d, J=8.9 Hz, 2H, H-14, H-18), 7.25 (d, J=
9.0 Hz, 2H, H-8, H-12), 6.90 (d, J=8.9 Hz, 2H, H-15, H-17), 5.58
(d, J1,2 =1.8 Hz, 1H, H-1), 4.04 (dd, J2,3 =3.4 Hz, J1,2 =1.9 Hz, 1H,
H-2), 3.92 (dd, J2,3 =3.4 Hz, J3,4 =9.5, 1H, H-3), 3.79–3.71 (m, 3H,
[D6]DMSO): d=160.7 (C-15, C-17), 159.5 (C-7), 147.4 (C-10),
145.7 (C-13), 124.7 (C-15, C-17), 124.0 (C-9, C-11) 117.1 (C-8, C-
12), 116.2 (C-14, C-18), 100.4 (C-1), 77.5 (C-5). 76.7 (C-3), 73.5
(C-2), 69.9 (C-4), 61.0 (C-6); IR (ATR): v˜ =3276, 2882, 1587, 1495,
1231; e=17871ꢂ788 Lmolꢁ1 cmꢁ1; MS (EI): m/z [M+H]+ calcd
for C18H20N2O7: 377.1, found: 377.1.
H-4, H-6a, H-6b), 3.60 (ddd, J4,5 =9.8 Hz, J5,6a =5.3 Hz, J5,6b
=
2.5 Hz, 1H, H-5); 13C NMR (125 MHz, CD3OD): d=161.7 (C-16),
159.7 (C-7), 149.4 (C-10), 147.5 (C-13), 125.6 (C-15, C-17), 124.9
(C-8, C-12), 117.9 (C-9, C-11), 116.7 (C-14, C-18), 100.2 (C-1), 75.6
(C-5), 72.4 (C-3), 71.9 (C-2), 68.3 (C-4), 62.7 (C-6); IR (ATR): v˜ =
3210, 1586, 1493, 1225 cmꢁ1; e=19804ꢂ750 Lmolꢁ1 cmꢁ1; MS
(MALDI-TOF): m/z [M+H]+ calcd for C18H20N2O7: 377.36, found:
377.17; HRMS: m/z [M+H]+ calcd for C18H20N2O7: 377.1343,
found: 377.1339.
Acknowledgements
We thank the Deutsche Forschungsgemeinschaft (Germany) for
financial support (collaborative network SFB 677) and Prof. A.
Tholey (Kiel) for high-resolution mass spectrometry. Art work of
Dipl.-Chem. Femke Beiroth is also gratefully acknowledged.
E-p-[p-(a-d-Mannopyranosyloxy)]phenylazophenyl a-d-man-
nopyranoside (29): Protected bis-glycoside 28 (100 mg,
0.114 mmol) was dissolved in dry MeOH (2 mL), and a catalytic
amount of NaOMe was added. The reaction mixture was stirred
at RT overnight, then neutralized with Amberlite IR 120 ion ex-
change resin and filtered. The filtrate was evaporated under re-
duced pressure to yield bivalent glycoside 29 as a yellow solid
(57 mg, 0.105 mmol, 93%): mp: 204–2068C; Rf =O.21 (CH2Cl2/
Keywords: azobenzene glycosides · carbohydrate orientation ·
glycosylation · Mills reaction · photoswitching
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1
MeOH, 6:4); [a]2D0 = +1.92 (c=0.9, DMSO); H NMR (600 MHz,
[D6]DMSO): d=7.84 (d, J=8.9 Hz, 4H, H-9, H-11, H-14, H-18),
7.26 (d, J=8.9 Hz, 4H, H-8, H-12, H-15, H-17), 5.51 (bs, 2H, 2 H-
1), 5.09 (d, J=4.3 Hz, 2H, 2 OH), 4.86 (d, J=5.8 Hz, 2H, 2 OH),
4.79 (d, J=5.9 Hz, 2H, 2OH), 4.47 (t, J=5.9 Hz, 2H, 2 OH), 3.87
(bs, 2H, 2 H-2), 3.70 (mc, 2H, 2 H-3), 3.60 (dd, J5,6a =10.1, J6a,6b
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5.8 Hz, 2 H-6a), 3.54–3.46 (m, 4H, 2 H-4, 2 H-6b), 3.40–3.36 (m,
2H, 2 H-5); 13C NMR (150 MHz, [D6]DMSO): d=158.6 (C-7, C-16),
146.9 (C-13, C-10), 124.51 (C-9, C-11, C-14, C-18), 117.1 (C-8, C-
12, C-15, C-17), 98.7 (2 C-1), 75.2 (2 C-5), 70.7 (2 C-3), 69.9 (2 C-
2), 66.7 (2 C-4), 61.0 (2 C-6); IR (ATR): v˜ =3301, 2914, 1599,
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1583, 1498, 1227 cmꢁ1
;
e=18810ꢂ252 Lmolꢁ1 cmꢁ1
;
MS
(MALDI-TOF): m/z [M+Na]+ calcd for C24H30N2O12: 561.50,
found: 561.26; HRMS: m/z [M+H]+ calcd for C24H30N2O12:
539.1871, found: 539.1860.
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E-p-(p-Hydroxyphenylazo)phenyl b-d-glucopyranoside (27):
Protected glycoside 25 (87 mg, 0.16 mmol) was dissolved in
dry MeOH (2 mL) and a catalytic amount of NaOMe was
added. The reaction mixture was stirred at RT overnight, then
neutralized with Amberlite IR 120 ion exchange resin and fil-
tered. The filtrate was evaporated under reduced pressure to
yield glycoside 27 as a yellow solid (53 mg, 0.14 mmol, 89%):
mp: 186–1888C; Rf =0.75 (EtOAc/MeOH 3:2), [a]2D0 =ꢁ3.42 (c=
0.92, DMSO); 1H NMR (500 MHz, [D6]DMSO): d=7.79 (d, J=
8.8 Hz, 2H, H-9, H-11), 7.75 (d, J=8.8 Hz, 2H, H-15, H-17), 7.18
(d, J=8.9 Hz, 2H, H-8, H-12), 6.93 (d, J=8.8 Hz, 2H, H-14, H-
18), 4.99 (d, J=7.3 Hz, 1H, H-1), 3.70 (dd, J=12.1, 1.9 Hz, 1H,
H-6a), 3.48 (dd. J=5.83, 12.1 Hz, 1H, H-6b), 3.39 (dt, J=2.0,
5.76 Hz, 1H, H-5), 3.30 (t, J=9.0 Hz, 1H H-3), 3.27 (t, J=8.3 Hz,
1H, H-2), 3.18 (d, J=7.9 Hz, 1H, H-4); 13C NMR (150 MHz,
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Phys. Chem. A 2009, 113, 13144–13151.
Received: April 15, 2014
ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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