Glucosinolate chemistry: Synthesis of O-glycosylated derivatives of glucosinalbin

Article abstract of DOI:10.1002/ejoc.201000246

The synthesis of the major glucosinolate of Moringa oleifera and of other non-natural O-glycosylated derivatives of glucosinalbin is reported. The synthetic sequence applied, which involves the conversion of carbohydrate-based nitrostyrenes into the key thiohydroximates, appears to be sufficiently versatile to synthesize a range of glucosinolates bearing a glycosylated phenolic function. We synthesized analogues of the naturally occurring L-rhamnoside 1 with a view to estimating the importance of this phenol-protecting sugar moiety in modulating the biological activity of the parent glucosinolate and related breakdown products.

Full text of DOI:10.1002/ejoc.201000246

FULL PAPER
DOI: 10.1002/ejoc.201000246
Glucosinolate Chemistry: Synthesis of O-Glycosylated Derivatives of
Glucosinalbin
David Gueyrard,*[a][‡] Renato Iori,[b] Arnaud Tatibouët,[a] and Patrick Rollin[a]
Keywords: Natural products / Carbohydrates / Glycosides / Hydroximates
The synthesis of the major glucosinolate of Moringa oleifera
and of other non-natural O-glycosylated derivatives of glu-
cosinalbin is reported. The synthetic sequence applied,
which involves the conversion of carbohydrate-based nitro-
styrenes into the key thiohydroximates, appears to be suffi-
ciently versatile to synthesize a range of glucosinolates
bearing a glycosylated phenolic function. We synthesized
analogues of the naturally occurring -rhamnoside 1 with a
view to estimating the importance of this phenol-protecting
sugar moiety in modulating the biological activity of the par-
ent glucosinolate and related breakdown products.
L
Compound 1 is a representative member of a restricted
group of glucosinolates, the aglycon of which bears an O-
glycosylated hydroxy function (Figure 2). The presence of a
(4Ј-O-acetyl)--rhamnosyl analogue of 1 was postulated in
Moringa peregrina[11] and other examples arise in the Rese-
daceae family: glucosinolate 3, an O-rhamnosylated form
of isoglucosinalbin 4, was identified in the genus Reseda,[12]
whereas 5, an O-arabinosylated derivative of glucobarbarin
6, was shown to be present in the genus Sesamoides.[13]
Introduction
Most species within the order Brassicales have been
shown to have significant effects on human health.[1,2] This
is mainly due to secondary metabolites known as glucosin-
olates and their breakdown products, mainly isothiocyanates,
oxazolidine-2-thiones and nitriles. Glucosinolates are natu-
rally occurring thiosaccharidic compounds found in all
families of Brassicales and can be hydrolysed by an atypical
glucohydrolase called myrosinase (E.C. 3.2.1.147) to pro-
duce -glucose and various compounds depending on the
nature of the aglycon moiety.[3]
Moringa oleifera (horseradish tree) is a multipurpose tree
that is used in a number of tropical countries[4] for human
and animal feeding and medicinal purposes.[5,6] Owing to
its bactericidal properties the plant is also currently em-
ployed for water purification.[7] Moringa oleifera extracts
have also been tested as anticancer,[8] antiinflammatory and
hepato-protective[9,10] agents. The seeds of the plant contain
8–10% of a structurally unusual glucosinolate (1), an O-
rhamnosylated form of p-hydroxybenzyl glucosinolate, that
is, glucosinalbin (2; Figure 1).
Figure 2. Other naturally occurring O-glycosylated glucosinolates.
Glucosinolate 1 (sometimes called glucomoringin) can be
hydrolysed by myrosinase to furnish a number of clearly
identified bioactive compounds (Scheme 1).[14–16] Isothiocy-
anate 7 (“moringin”) was recently shown to inhibit NF-kB
and to reduce myeloma growth,[17] whereas related thiono-
carbamates 8a,b have strong activity as hypotensive
agents[15a] or antitumour promoters.[18]
Figure 1. Glucosinalbin (2) and its glycosylated analogue 1 isolated
from Moringa oleifera.
[a] Institut de Chimie Organique et Analytique, Université
d’Orléans,
BP 6759, 45067 Orléans Cedex 2, France
E-mail: david.gueyrard@univ-lyon1.fr
[b] Agricultural Research Council – Research Centre for Industrial
Crops (CRA-CIN),
Via di Corticella 133, 40129 Bologna, Italy
[‡] Current address: ICBMS – UMR 5246, Université Claude
Bernard Lyon 1,
Glucosinalbin is one of the few glucosinolates in which
the aglycon chain bears a phenolic group. Bearing in mind
the prominent position of phenol glycosides in the vegetable
43 bd du 11 novembre 1918, 69622 Villeurbanne Cedex, France kingdom,[19] we planned to synthesize analogues of the nat-
Eur. J. Org. Chem. 2010, 3657–3664
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3657

D. Gueyrard, R. Iori, A. Tatibouët, P. Rollin
FULL PAPER
urally occurring -rhamnoside 1 with a view to estimating
the importance of this phenol-protected sugar moiety in
modulating the biological activity of the parent glucosinol-
ate and the related breakdown products. In our earlier com-
munication[20] we reported a synthesis of 1 involving the
standard coupling of O-protected 1-thio-β--glucopyranose
with the appropriate -rhamnosylated hydroximoyl chlo-
ride. In this paper, we report the detailed synthesis of 1 and
four O-glycosylated derivatives of glucosinalbin bearing a
β--gluco, β--galacto, β-cellobio and α--manno unit.
Scheme 1. Bioactive compounds resulting from myrosinase hydrol-
ysis of 1.
Scheme 2. Preparation of the nitrovinyl precursors.
3658
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3657–3664

Synthesis of O-Glycosylated Derivatives of Glucosinalbin
11 was readily effected by using a variation of the Henry
reaction.[24] Alternative protocols were used to prepare the
other glycosides.
Results and Discussion
Our strategy requires the preparation of nitrostyrene pre-
cursors connected to sugar frameworks (Scheme 2). The
The glucose and galactose derivatives were obtained
previously described aryl α--rhamnoside 10[21] was first from α-bromo-glycosyl donors 12 and 15, respectively, un-
obtained in nearly 60% yield from the corresponding thio- der standard conditions[25] to produce in moderate-to-good
glycoside 9[22] through a slight modification of Leuck and yields the O-glycoside aldehydes 13 and 16, which were
Kunz’s method.[23] Conversion of 10 into the nitrostyrene readily converted into nitrovinyl precursors 14 and 17. The
Scheme 3. Preparation of the key thiohydroximates 22–26.
Scheme 4. Synthesis of 1 and glucosinolates 32–35.
Eur. J. Org. Chem. 2010, 3657–3664
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3659

D. Gueyrard, R. Iori, A. Tatibouët, P. Rollin
FULL PAPER
tri-O-acetyl-1-thio-α--rhamnopyranoside and p-hydroxybenzalde-
hyde using a slight modification of the pent-4-enyl thioglycoside
procedure previously described by Leuck and Kunz.[23]
cellobiose and mannose derivatives were prepared from per-
O-acetates 18 and 20 by a classic Lewis acid-catalysed gly-
cosylation[26] of p-hydroxy-2-nitrostyrene[24] to directly pro-
duce nitrovinyl precursors 19 and 21, respectively, in rather
low-to-moderate yields.
By submitting the nitrovinyl precursors to standard
Kulkarni-type conditions,[27] the corresponding hydroxim-
oyl chlorides were prepared and treated immediately
with 2,3,4,6-tetra-O-acetyl-1-thio-β--glucopyranose under
mildly basic conditions. The (Z)-thiohydroximates 22–26
were stereospecifically obtained in overall yields of 59–73%
(Scheme 3).
Final conversion of the thiohydroximates 22–26 into the
target glucosinolates 1 and 32–35 was performed according
to a previously described protocol.[28] O-Sulfation of the hy-
droximino moiety with the sulfur trioxide–pyridine complex
followed by quenching with aqueous potassium hydrogen
carbonate afforded the per-O-acetylated glucosinolates 27–
31, which were readily deprotected under basic conditions
to 1 and 32–35 (Scheme 4).
Typical Procedure for the Synthesis of the p-Nitrostyryl Glycosides
11, 14 and 17: A mixture of 10 (0.085 g, 0.215 mmol) and dry am-
monium acetate (0.018 g, 1.1 equiv.) in nitromethane (3 mL) was
stirred under reflux for 2 h and then the solvent was evaporated
under reduced pressure. Chromatographic purification (petroleum
ether/AcOEt, 7:3) of the residue provided the nitrostyryl derivative
11.
(E)-p-(2Ј,3Ј,4Ј-Tri-O-acetyl-α-L-rhamnopyranosyloxy)-2-nitro-
styrene (11): Yellow syrup (0.078 g, 83 %). [α]D = –111 (c 1.0,
1
CHCl3). H NMR (250 MHz, CDCl3): δ = 1.18 (d, J6a,5 = 6.2 Hz,
3 H, 6-H), 2.01, 2.04, 2.18 (3 s, 9 H, CH3CO), 3.91 (m, 1 H, 5-H),
5.15 (t, Jvic = 9.8 Hz, 1 H, 4-H), 5.40–5.51 (m, 3 H, 1-H, 2-H, 3-
H), 7.13 (d, Jvic = 8.9 Hz, 2 H, 2-Har, 6-Har), 7.51 (d, Jvic = 8.9 Hz,
2 H, 3-Har, 5-Har), 7.53 (d, Jvic = 13.6 Hz, 1 H, 2-Hvinyl), 7.95 (d,
Jvic = 13.6 Hz, 1 H, 1-Hvinyl) ppm. 13C NMR (62.89 MHz, CDCl3):
δ = 17.8 (C-6), 21.1, 21.2, 21.4 (CH3CO), 68.0 (C-5), 69.1, 69.8 (C-
2, C-3), 71.0 (C-4), 95.8 (C-1), 117.5 (aryl C-2, C-6), 124.9 (aryl C-
4), 131.5 (aryl C-3, C-5), 136.3, 138.8 (vinyl C-1, C-2), 159.1 (aryl
C-1), 170.3, 170.5 (CH3CO) ppm. MS (IS+): m/z = 438 [M + H]+,
455 [M + NH4]+, 460 [M + Na]+, 476 [M + K]+. HRMS (ESI):
calcd. for C20H23NNaO10 460.1214; found 460.1198.
Conclusions
We have reported herein the synthesis of the major gluco-
sinolate of Moringa oleifera, a promising tropical plant with
a wide range of applications. By copying this nitrovinyl pre-
cursor approach, the synthesis was extended to other O-
glycosylated derivatives of glucosinalbin with a view to esti-
mating the influence of the phenol-protecting sugar moiety
on the behaviour of the parent glucosinolate. Modulation
of the bioactivity of these O-glycosylated glucosinalbins
and the related breakdown products is under investigation.
(E)-p-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-β-D-glucopyranosyloxy)-2-nitro-
styrene (14): Yellow solid (0.481 g, 88%); m.p. 166–168 °C (EtOH).
[α]D = –24 (c = 1.0, CHCl3). 1H NMR (250 MHz, CDCl3): δ =
2.04, 2.06, 2.07 (3 s, 12 H, CH3CO), 3.91 (m, 1 H, 5-H), 4.18 (dd,
J6b,5 = 2.3, J6a,6b = 12.0 Hz, 1 H, 6b-H), 4.29 (dd, J6a,6b = 12.0,
J6a,5 = 5.3 Hz, 1 H, 6a-H), 5.11–5.36 (m, 4 H, 1-H, 2-H, 3-H, 4-
H), 7.20 (d, Jvic = 8.8 Hz, 2 H, 2-Har, 6-Har), 7.51 (d, Jvic = 8.8 Hz,
2 H, 3-Har, 5-Har), 7.53 (d, Jvic = 13.5 Hz, 1 H, 2-Hvinyl), 7.97 (d,
Jvic = 13.5 Hz, 1 H, 1-Hvinyl) ppm. 13C NMR (62.89 MHz, CDCl3):
δ = 20.5, 20.6, 20.7, 20.9 (CH3CO), 61.9 (C-6), 68.6 (C-4), 71.1 (C-
2), 72.3, 72.6 (C-3, C-5), 98.3 (C-1), 117.5 (aryl C-2, C-6), 125.0
(aryl C-4), 131.0 (aryl C-3, C-5), 136.2, 138.3 (vinyl C-1, C-2), 159.6
(aryl C-1), 169.3, 169.4, 170.2, 170.5 (CH3CO) ppm. MS (IS+): m/z
= 513.5 [M + NH4]+, 518.5 [M + Na]+, 534.5 [M + K]+. HRMS
(ESI): calcd. for C22H25NNaO12 518.1269; found 518.1251.
Experimental Section
General: Anhydrous reactions were performed in predried flasks
using anhydrous solvents (which were distilled when necessary ac-
cording to a literature procedure[29]) under argon. All chemicals
obtained from commercial suppliers were used without further pu-
rification. TLC was performed by using precoated aluminium-
backed plates (Merck Kieselgel 60F254), which were visualized by
UV light (254 nm) and by charring after exposure to a 5% H2SO4
solution in ethanol. Flash column chromatography was performed
using silica gel (36–63 mesh, E. Merck). Melting points were deter-
mined with a Kofler hot-stage apparatus. Optical rotations were
measured at 20 °C with a Perkin–Elmer 141 polarimeter. NMR
spectra were recorded with a Bruker DPX 250 (250 MHz for 1H
and 62.89 MHz for 13C) or AMX 500 (500 MHz for 1H and
125.7 MHz for 13C) spectrometer. Chemical shifts are expressed in
parts per million (ppm) downfield from TMS. Coupling patterns
(E)-p-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-β-D-galactopyranosyloxy)-2-nitro-
styrene (17): Yellow syrup (0.324g, 75 %). [α]D = +7 (c = 1.0,
CHCl3). 1H NMR (250 MHz, CDCl3): δ = 2.01, 2.03, 2.05, 2.18 (4
s, 12 H, CH3CO), 4.06–4.26 (m, 3 H, 5-H, 6-H), 5.10–5.16 (m, 2
H, 1-H, 3-H), 5.46–5.54 (m, 2 H, 2-H, 4-H), 7.05 (d, Jvic = 8.8 Hz,
2 H, 2-Har, 6-Har), 7.50 (d, Jvic = 8.8 Hz, 2 H, 3-Har, 5-Har), 7.53
(d, Jvic = 13.6 Hz, 1 H, 2-Hvinyl), 7.97 (d, Jvic = 13.6 Hz, 1 H, 1-
Hvinyl) ppm. 13C NMR (62.89 MHz, CDCl3): δ = 20.6, 20.7, 21.0
(CH3CO), 61.3 (C-6), 66.7 (C-4), 68.4 (C-2), 69.6 (C-3), 71.3 (C-5),
98.7 (C-1), 117.4 (aryl C-2, C-6), 125.0 (aryl C-4), 131.0 (aryl C-3,
C-5), 136.1, 138.3 (vinyl C-1, C-2), 159.6 (aryl C-1), 169.3, 170.1,
170.3 (CH3CO) ppm. MS (IS+): m/z = 518.5 [M + Na]+. HRMS
(ESI): calcd. for C22H25NNaO12 518.1269; found 518.1253.
1
in the H NMR spectra are designated as s = singlet, d = doublet,
t = triplet, q = quartet and m, multiplet and coupling constants are
given in Hz. NMR peak assignments were established by NOESY,
COSY, HSQC and HMBC methods for all reported compounds.
Mass spectra were recorded with an API-300 spectrometer [Ion-
spray® (IS) or heated nebulizer (HN) ionization mode]. HRMS
were recorded with a MicrOTOF-QII spectrometer (ESI mode).
Typical Procedure for the Synthesis of the p-Nitrostyryl Glycosides
19 and 21: BF3·Et2O (0.75 mL, 4 equiv.) was added to a solution
of 1,2,3,6,2Ј,3Ј,4Ј,6Ј-octa-O-acetyl-β-cellobiose (1.00 g, 1.47 mmol)
and commercial p-hydroxy-2-nitrostyrene (0.243 g, 1 equiv.) in
dichloromethane (10 mL) and the reaction mixture was stirred for
3 d at room temperature. After hydrolysis and extraction of the
aqueous phase with dichloromethane (ϫ3), the combined organic
layers were dried with magnesium sulfate and the solvent was evap-
4-(2Ј,3Ј,4Ј-Tri-O-acetyl-α-
L-rhamnopyranosyloxy)benzaldehyde
(10): Compound 10 was prepared in 59% yield from phenyl 2,3,4-
3660
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3657–3664

Synthesis of O-Glycosylated Derivatives of Glucosinalbin
orated under reduced pressure. Chromatographic purification
(CH2Cl2/MeOH, 19:1) of the residue provided compound 19.
CDCl3): δ = 17.5 (C-6Ј), 20.5, 20.6, 20.7, 20.9 (CH3CO), 38.0
(CH2Ar), 62.2 (C-6), 67.2 (C-5Ј), 68.0 (C-4), 68.9, 69.7 (C-2Ј, C-
3Ј), 70.0 (C-2), 70.9 (C-4Ј), 73.7 (C-3), 75.7 (C-5), 79.4 (C-1), 95.9
(C-1Ј), 116.9 (aryl C-2, C-6), 129.2 (aryl C-3, C-5), 129.9 (aryl C-
4), 155.2 (aryl C-1), 169.1, 169.3, 170.1, 170.5 (CH3CO, C-7) ppm.
MS (IS+): m/z = 786.5 [M + H]+, 808.5 [M + Na]+, 824.5 [M +
K]+. HRMS (ESI): calcd. for C34H43NNaO18S 808.2093; found
808.2058.
(E)-p-(2Ј,3Ј,6Ј,2ЈЈ,3ЈЈ,4ЈЈ,6ЈЈ-Hepta-O-acetyl-β-cellobiosyloxy)-2-
nitrostyrene (19): Yellow solid (0.387 g, 34 %); m.p. 218–220 °C
(EtOH). [α]D = –23 (c = 1.0, CHCl3). 1H NMR (250 MHz, CDCl3):
δ = 1.99, 2.02, 2.05, 2.06, 2.09, 2.10 (6 s, 21 H, CH3CO), 3.66 (m,
1 H, 5Ј-H), 3.82–3.92 (m, 2 H, 4Ј-H, 5ЈЈ-H), 4.03–4.17 (m, 2 H,
6bЈ-H, 6bЈЈ-H), 4.39 (dd, J6aЈЈ,5ЈЈ = 4.5, J6aЈЈ,6bЈЈ = 12.4 Hz, 1 H,
6aЈЈ-H), 4.54 (m, 2 H, 1ЈЈ-H, 6aЈ-H), 4.95 (t, Jvic = 7.9 Hz, 1 H,
2ЈЈ-H), 5.04–5.32 (m, 5 H, 1Ј-H, 2Ј-H, 3Ј-H, 3ЈЈ-H, 4ЈЈ-H), 7.02 (d,
Jvic = 8.7 Hz, 2 H, 2-Har, 6-Har), 7.50 (d, 2 H, 3-Har, 5-Har), 7.53
(d, Jvic = 13.6 Hz, 1 H, 2-Hvinyl), 7.97 (d, Jvic = 13.6 Hz, 1 H, 1-
S-[p-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-β-
acetohydroximoyl]-2,3,4,6-tetra-O-acetyl-1-thio-β-
D
-glucopyranosyloxy)phenyl-
-glucopyranose
D
(23): White solid (0.332 g, 59%); m.p. 124–126 °C (Et2O/petroleum
ether, 1:1). [α]D = –12 (c = 1.0, CHCl3). 1H NMR (250 MHz,
CDCl3): δ = 1.97, 2.00, 2.02, 2.03, 2.04, 2.06, 2.07 (7 s, 24 H,
CH3CO), 3.54 (m, 1 H, 5-H), 3.89 (m, 3 H, 5Ј-H, CH2Ar), 4.00–
4.33 (m, 4 H, 6-H, 6Ј-H), 4.84 (d, J1,2 = 9.7 Hz, 1 H, 1-H), 4.93–
5.35 (m, 7 H, 2-H, 3-H, 4-H, 1Ј-H, 2Ј-H, 3Ј-H, 4Ј-H), 6.97 (d, Jvic
= 8.5 Hz, 2 H, Har), 7.18 (d, Jvic = 8.5 Hz, 2 H, Har), 8.55 (s, 1 H,
NOH) ppm. 13C NMR (62.89 MHz, CDCl3): δ = 20.5, 20.6, 20.7
(CH3CO), 38.0 (CH2Ar), 61.9, 62.2 (C-6, C-6Ј), 70.0 (C-2), 68.0,
68.2, 71.1, 72.7 (C-4, C-2Ј, C-3Ј, C-4Ј), 72.0 (C-5Ј), 73.6 (C-3), 75.7
(C-5), 79.4 (C-1), 99.1 (C-1Ј) 117.5 (aryl C-2, C-6), 129.3 (aryl C-
3, C-5), 130.6 (aryl C-4), 156.0 (aryl C-1), 169.1, 169.3, 169.4,
170.2, 170.3, 170.5, 170.6 (CH3CO, C-7) ppm. MS (IS+): m/z =
844.5 [M + H]+, 866.5 [M + Na]+, 882.5 [M + K]+. HRMS (ESI):
calcd. for C36H45NNaO20S 866.2148; found 866.2129.
H
vinyl) ppm. 13C NMR (62.89 MHz, CDCl3): δ = 20.5, 20.7
(CH3CO), 61.5, 61.8 (C-6Ј, C-6ЈЈ), 67.7, 71.2, 71.6, 72.0, 72.3, 72.9,
73.1, 76.2 (C-2Ј, C-3Ј, C-4Ј, C-5Ј, C-2ЈЈ, C-3ЈЈ, C-4ЈЈ, C-5ЈЈ), 98.0,
100.8 (C-1Ј, C-1ЈЈ), 117.4 (aryl C-2, C-6), 125.0 (aryl C-4), 130.9
(aryl C-3, C-5), 136.1, 138.2 (vinyl C-1, C-2), 159.5 (aryl C-1),
169.0, 169.3, 169.5, 169.7, 170.1, 170.2, 170.5 (CH3CO) ppm. MS
(IS+): m/z = 801.5 [M + NH4]+, 806.5 [M + Na]+. HRMS (ESI):
calcd. for C34H41NNaO20 806.2114; found 806.2138.
(E)-p-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-α-D-mannopyranosyloxy)-2-nitro-
styrene (21): Yellow solid (2.005 g, 66%); m.p. 164–166 °C (EtOH).
[α]D = +118 (c = 1.0, CHCl3). 1H NMR (250 MHz, CDCl3): δ =
2.03, 2.05, 2.06, 2.21 (4 s, 12 H, CH3CO), 4.01–4.10 (m, 2 H, 5-H,
6b-H), 4.27 (dd, J6a,5 = 5.3, J6a,6b = 12.6 Hz, 1 H, 6a-H), 5.38 (t,
J3,4 = 10.2 Hz, 1 H, 4-H), 5.45 (dd, J1,2 = 1.9, J2,3 = 3.4 Hz, 1 H,
2-H), 5.55 (dd, 1 H, 3-H), 5.59 (d, J1,2 = 1.9 Hz, 1 H, 1-H), 7.16
(d, Jvic = 8.9 Hz, 2 H, 2-Har, 6-Har), 7.52 (d, 2 H, 3-Har, 5-Har),
7.54 (d, Jvic = 13.6 Hz, 1 H, 2-Hvinyl), 7.97 (d, Jvic = 13.6 Hz, 1
H, 1-Hvinyl) ppm. 13C NMR (62.89 MHz, CDCl3): δ = 20.6, 20.8
(CH3CO), 61.9 (C-6), 65.6 (C-4), 68.6 (C-3), 69.0 (C-2), 69.5 (C-5),
95.5 (C-1), 117.1 (aryl C-2, C-6), 124.8 (aryl C-4),130.9 (aryl C-3,
C-5), 136.1, 138.2 (vinyl C-1, C-2), 158.4 (aryl C-1), 169.6, 169.9,
170.4 (CH3CO) ppm. MS (IS+): m/z = 496.5 [M + H]+, 518.5 [M
+ Na]+. HRMS (ESI): calcd. for C22H25NNaO12 518.1269; found
518.1262.
S-[p-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-β-D-galactopyranosyloxy)phenylace-
tohydroximoyl]-2,3,4,6-tetra-O-acetyl-1-thio-β-
D
-glucopyranose
(24): Colourless syrup (0.205 g, 60%). [α]D = –2 (c = 1.0, CHCl3).
1H NMR (250 MHz, CDCl3): δ = 1.97, 2.00, 2.03, 2.05, 2.07, 2.17
(7 s, 24 H, CH3CO), 3.53 (m, 1 H, 5-H), 3.89 (s, 2 H, CH2Ar),
3.99–4.26 (m, 5 H, 5Ј-H, 6-H, 6Ј-H), 4.84 (d, J1,2 = 9.8 Hz, 1 H, 1-
H), 4.93–5.16 (m, 5 H, 2-H, 3-H, 4-H, 1Ј-H, 3Ј-H), 5.44–5.51 (m,
2 H, 2Ј-H, 4Ј-H), 6.98 (d, Jvic = 8.5 Hz, 2 H, Har), 7.18 (d, Jvic
=
8.5 Hz, 2 H, Har), 8.65 (s, 1 H, NOH) ppm. 13C NMR (62.89 MHz,
CDCl3): δ = 20.5, 20.6, 20.7, 20.8, 21.0 (CH3CO), 38.0 (CH2Ar),
61.2, 62.1 (C-6, C-6Ј), 68.0 (C-4), 66.9 (C-4Ј), 68.7 (C-2Ј), 70.0 (C-
2), 70.8 (C-3Ј), 71.0 (C-5Ј), 73.6 (C-3), 75.7 (C-5), 79.4 (C-1), 99.7
(C-1Ј), 117.5 (aryl C-2, C-6), 129.3 (aryl C-3, C-5), 130.5 (aryl C-
4), 156.1 (aryl C-1), 169.1, 169.3, 169.5, 170.1, 170.2, 170.3, 170.5,
171.3 (CH3CO, C-7) ppm. MS (IS+): m/z = 844.5 [M + H]+. HRMS
(ESI): calcd. for C36H45NNaO20S 866.2148; found 866.2142.
Typical Procedure for the Synthesis of the Thiohydroximate Precur-
sors 22–26: Triethylsilane (60 µL, 2.1 equiv.) and titanium tetra-
chloride (43 µL, 2.2 equiv.) were added. to a solution of p-nitrosty-
ryl glycoside 11 (0.078 g, 0.178 mmol) in dichloromethane (10 mL).
After 18 h stirring at room temperature, the reaction mixture was
hydrolysed and the aqueous phase extracted with dichloromethane
(ϫ2). The combined organic layers were dried with magnesium sul-
fate and the solvent was evaporated under reduced pressure. The
residue was dissolved again in dichloromethane (10 mL) and then
commercial 2,3,4,6-tetra-O-acetyl-1-thio-β--glucopyranose
(0.078 g, 1.2 equiv.) and triethylamine (0.075 mL, 3 equiv.) were
successively added. After stirring for 1 h at room temperature, the
solvent was evaporated in vacuo. Chromatographic purification
(petroleum ether/AcOEt, 1:1) of the residue provided compound
22.
S-[p-(2Ј,3Ј,6Ј,2ЈЈ,3ЈЈ,4ЈЈ,6ЈЈ-Hepta-O-acetyl-β-cellobiosyloxy)phenyl-
acetohydroximoyl]-2,3,4,6-tetra-O-acetyl-1-thio-β-D-glucopyranose
(25): White solid (0.527 g, 73%); m.p. 182–184 °C (Et2O/petroleum
ether, 1:1). [α]D = –19 (c = 1.0, CHCl3). 1H NMR (250 MHz,
CDCl3): δ = 1.95, 1.98, 1.99, 2.01, 2.04, 2.07, 2.08 (8 s, 33 H,
CH3CO), 3.49 (m, 1 H, 5-H), 3.66 (m, 1 H, 5ЈЈ-H), 3.73–3.89 (m,
2 H, 4Ј-H, 5Ј-H), 3.86 (s, 2 H, CH2Ar), 3.95–4.01 (m, 2 H, 6-H),
4.04–4.16 (m, 2 H, 6bЈ-H, 6bЈЈ-H), 4.36 (dd, J6aЈЈ,5ЈЈ = 4.5, J6aЈЈ,6bЈЈ
= 12.6 Hz, 1 H, 6aЈЈ-H), 4.49–4.53 (m, 2 H, 1ЈЈ-H, 6aЈ-H), 4.79–
5.29 (m, 10 H, 1-H, 2-H, 3-H, 4-H, 1Ј-H, 2Ј-H, 3Ј-H, 2ЈЈ-H, 3ЈЈ-H,
4ЈЈ-H), 6.93 (d, Jvic = 8.5 Hz, 2 H, Har), 7.16 (d, Jvic = 8.5 Hz, 2
H, Har), 8.75 (s, 1 H, NOH) ppm. 13C NMR (62.89 MHz, CDCl3):
δ = 20.4, 20.5, 20.7 (CH3CO), 37.9 (CH2Ar), 61.4, 61.8, 62.1 (C-6,
C-6Ј, C-6ЈЈ), 67.6, 67.8, 69.9, 71.2, 71.4, 71.8, 72.3, 72.8, 73.5, 75.5,
76.2 (C-2, C-3, C-4, C-5, C-2Ј, C-3Ј, C-4Ј, C-5Ј, C-2ЈЈ, C-3ЈЈ, C-
S-[p-(2Ј,3Ј,4Ј-Tri-O-acetyl-α-
L-rhamnopyranosyloxy)phenylacetohy-
droximoyl]-2,3,4,6-tetra-O-acetyl-1-thio-β-
D
-glucopyranose (22):
White solid (0.091 g, 65 %); m.p. 104–106 °C (Et2O/petroleum
ether, 1:1). [α]D = –45 (c = 1.0, CHCl3). 1H NMR (250 MHz,
CDCl3): δ = 1.22 (d, J6Ј,5Ј = 6.2 Hz, 3 H, 6Ј-H), 1.97, 1.98, 2.02,
2.03, 2.04, 2.09, 2.19 (7 s, 21 H, CH3CO), 3.54 (m, 1 H, 5-H), 3.91 4ЈЈ, C-5ЈЈ), 79.2 (C-1), 98.7, 100.7 (C-1Ј, C-1ЈЈ), 117.3 (aryl C-2, C-
(s, 2 H, CH2Ar), 3.99–4.21 (m, 3 H, 6-H, 5Ј-H), 4.81 (d, J1,2
9.6 Hz, 1 H, 1-H), 4.93–5.08 (m, 3 H, 2-H, 3-H, 4-H), 5.16 (t, Jvic
=
6), 129.1 (aryl C-3, C-5), 130.6 (aryl C-4), 155.8 (aryl C-1), 169.0,
169.2, 169.3, 169.5, 169.7, 170.0, 170.1, 170.2, 170.4, 170.5
= 9.8 Hz, 1 H, 4Ј-H), 5.43–5.55 (m, 3 H, 1Ј-H, 2Ј-H, 3Ј-H), 7.07 (CH3CO, C-7) ppm. MS (IS+): m/z = 1132.5 [M + H]+, 1149.5 [M
(d, Jvic = 8.7 Hz, 2 H, 2-Har, 6-Har), 7.20 (d, Jvic = 8.7 Hz, 2 H, 3- + NH4 ]+ , 1154. 5 [M + Na]+ . HRMS (ESI): calcd. for
Har, 5-Har), 8.41 (s, 1 H, NOH) ppm. 13C NMR (62.89 MHz,
C41H61NNaO28S 1154.2993; found 1154.2942.
Eur. J. Org. Chem. 2010, 3657–3664
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3661

D. Gueyrard, R. Iori, A. Tatibouët, P. Rollin
FULL PAPER
S-[p-(2Ј,3Ј,4Ј,6Ј-Tetra-O-acetyl-α-
acetohydroximoyl]-2,3,4,6-tetra-O-acetyl-1-thio-β-
D
-mannopyranosyloxy)phenyl-
-glucopyranose
8.3 Hz, 2 H, Har), 7.28 (d, Jvic = 8.3 Hz, 2 H, Har) ppm. 13C NMR
(62.89 MHz, [D6]DMSO): δ = 20.9, 21.0, 21.1, 21.2 (CH3CO), 36.9
(CH2Ar), 62.0, 62.2 (C-6, C-6Ј), 68.3 (C-4), 67.9, 69.0 (C-2Ј, C-4Ј),
70.2 (C-2), 70.9 (C-3Ј, C-5Ј), 73.5 (C-3), 75.0 (C-5), 79.0 (C-1), 98.5
(C-1Ј), 117.2 (aryl C-2, C-6), 130.3 (aryl C-3, C-5), 131.1 (aryl C-
4), 156.1 (aryl C-1), 153.3 (C-7), 169.8, 169.9, 170.0, 170.2, 170.3,
170.6, 170.7 (CH3CO) ppm. MS (IS–): m/z = 922.5 [M – K]+.
D
(26): White solid (0.859 g, 72%); m.p. 102–104 °C (Et2O/petroleum
ether, 1:1). [α]D = +31 (c = 1.0, CHCl3). 1H NMR (250 MHz,
CDCl3): δ = 1.93, 1.98, 2.00, 2.04, 2.17 (6s, 24 H, CH3CO), 3.52
(m, 1 H, 5-H), 3.86 (s, 2 H, CH2Ar), 3.95–4.29 (m, 5 H, 5Ј-H, 6-
H, 6Ј-H), 4.75 (d, J1,2 = 9.8 Hz, 1 H, 1-H), 4.88–5.03 (m, 3 H, 2-
H, 3-H, 4-H), 5.36 (t, J3Ј,4Ј = 10.0 Hz, 1 H, 4Ј-H), 5.43 (dd, J2Ј,3Ј HRMS (ESI): calcd. for C36H44NO23S2 922.1751; found 922.1762.
= 3.4 Hz, 1 H, 2Ј-H), 5.52 (d, J1Ј,2Ј = 1.9 Hz, 1 H, 1Ј-H), 5.54 (dd,
Per-O-acetylated 4Ј-O-(β-Cellobiosyl) Glucosinalbin (30): White
1 H, 3Ј-H), 7.03 (d, Jvic = 8.7 Hz, 2 H, Har), 7.16 (d, Jvic = 8.7 Hz,
amorphous solid (0.143 g, 49%); m.p. 172–174 °C. [α]D = –14 (c =
1.0, MeOH). 1H NMR (250 MHz, [D6]DMSO): δ = 1.91, 1.92,
1.93, 1.96, 1.98, 1.99, 2.01, 2.06 (8 s, 33 H, CH3CO), 3.63–4.00 (m,
10H, 4Ј-H, 5-H, 5Ј-H, 5ЈЈ-H, 6a-H, 6b-H, 6bЈ-H, 6bЈЈ-H, CH2Ar),
4.11–4.25 (m, 2 H, 6aЈ-H, 6aЈЈ-H), 4.52 (dd, J = 9.7, J = 7.8 Hz, 1
H, 4ЈЈ-H), 4.65–4.86 (m, 5 H, 1-H, 2-H, 3-H, 4-H, 1ЈЈ-H), 5.09–
5.21 (m, 4 H, 2Ј-H, 3Ј-H, 2ЈЈ-H, 3ЈЈ-H), 5.34 (d, J1Ј,2Ј = 7.8 Hz, 1
H, 1Ј-H), 6.82 (d, Jvic = 8.5 Hz, 2 H, Har), 7.15 (d, Jvic = 8.5 Hz, 2
H, Har) ppm. 13C NMR (62.89 MHz, [D6]DMSO): δ = 20.3, 20.4,
20.5, 20.7 (CH3CO), 37.4 (CH2Ar), 61.5, 62.0 (C-6, C-6Ј, C-6ЈЈ),
67.7, 69.6, 70.5, 70.9, 71.2, 72.2, 72.8, 74.3, 76.5 (C-2, C-3, C-4, C-
5, C-2Ј, C-3Ј, C-4Ј, C-5Ј, C-2ЈЈ, C-3ЈЈ, C-4ЈЈ, C-5ЈЈ), 78.4 (C-1),
96.9, 99.6 (C-1Ј, C-1ЈЈ), 116.3 (aryl C-2, C-6), 129.6 (aryl C-3, C-
5), 130.4 (aryl C-4), 155.4 (aryl C-1), 152.6 (C-7), 169.1, 169.2,
169.5, 169.6, 170.0, 170.1, 170.3 (CH3CO) ppm. MS (IS–): m/z =
1211 [M – K]+. HRMS (ESI): calcd. for C48H60NO31S2 1210.2596;
found 1210.2600.
2 H, Har), 9.07 (s, 1 H, NOH) ppm. 13C NMR (62.89 MHz,
CDCl3): δ = 20.5, 20.6, 20.7, 20.9 (CH3CO), 38.0 (CH2Ar), 62.0,
62.3 (C-6, C-6Ј), 65.8 (C-4Ј), 68.1 (C-4), 68.9 (C-3Ј), 69.2 (C-2Ј),
69.3 (C-5Ј), 70.0 (C-2), 73.6 (C-3), 75.7 (C-5), 79.4 (C-1), 96.0 (C-
1Ј), 116.9 (aryl C-2, C-6), 129.3 (aryl C-3, C-5), 130.2 (aryl C-4),
155.0 (aryl C-1), 169.1, 169.3, 169.8, 170.0, 170.2, 170.5, 170.6
(CH3CO, C-7) ppm. MS (IS+): m/z = 844.5 [M + H]+, 866.5 [M +
Na]+. HRMS (ESI): calcd. for C36H45NNaO20S 866.2148; found
866.2118.
Typical Procedure for the Synthesis of the O-Sulfated Thiohydroxim-
ates 27–31: Sulfur trioxide–pyridine complex (176 mg, 5 equiv.) was
added to a solution of compound 22 (0.174 g, 0.221 mmol) in
DMF (3 mL). After 18 h stirring at 50 °C the reaction mixture was
treated with an aqueous solution of KHCO3 (0.2 , 5 mL) and then
the solvents were evaporated in vacuo. Chromatographic purifica-
tion (AcOEt/MeOH, 17:3) of the residue provided compound 27.
Per-O-acetylated 4Ј-O-(α-
Amorphous solid (0.115 g, 58%). [α]D = –19 (c = 1.0, MeOH). H White amorphous solid (0.187 g, 80%); m.p. 150–152 °C. [α]D
NMR (250 MHz, [D6]DMSO): δ = 1.06 (d, J6Ј,5Ј = 6.0 Hz, 3 H, 6Ј- +32 (c = 1.0, MeOH). 1H NMR (250 MHz, [D6]DMSO): δ = 1.92,
L-Rhamnopyranosyl) Glucosinalbin (27): Per-O-acetylated 4Ј-O-(α-D-Mannopyranosyl) Glucosinalbin (31):
1
=
H), 1.92, 1.93, 1.96, 2.03, 2.13 (5 s, 21 H, CH3CO), 3.69–4.08 (m,
6 H, 5-H, 5Ј-H, 6-H CH2Ar), 4.77–4.99 (m, 4 H, 1-H, 2-H, 3-H,
1.93, 1.94, 1.99, 2.02, 2.13 (6 s, 24 H, CH3CO), 3.70 (m, 1 H, 5-
H), 3.91–4.18 (m, 7 H, CH2Ar, 5Ј-H, 6-H, 6Ј-H), 4.76–4.94 (m, 2
H), 5.13–5.33 (m, 5 H), 5.70 (s, 1 H, 1Ј-H), 7.12 (d, Jvic = 8.5 Hz,
2 H, Har); 7.30 (d, Jvic = 8.5 Hz, 2 H, Har) ppm. 13C NMR
4-H), 5.21–5.39 (m, 4 H, 1Ј-H, 2Ј-H, 3Ј-H, 4Ј-H), 7.11 (d, Jvic
=
8.3 Hz, 2 H, 2-Har, 6-Har), 7.30 (d, Jvic = 8.3 Hz, 2 H, 3-Har, 5-
Har) ppm. 13C NMR (62.89 MHz, [D6]DMSO): δ = 18.0 (C-6Ј), (62.89 MHz, [D6]DMSO): δ = 20.2, 20.3, 20.4, 20.6 (CH3CO), 36.3
21.1, 21.2, 21.3, 21.5 (CH3CO), 37.1 (CH2Ar), 62.4 (C-6), 67.6 (C-
5Ј), 68.5 (C-4), 69.3, 69.5 (C-2Ј, C-3Ј), 70.3 (C-2), 70.7 (C-4Ј), 73.6
(CH2Ar), 61.3 (C-6, C-6Ј), 65.2 (C-4Ј), 67.7 (C-4), 68.4 (C-3Ј), 68.5
(C-2Ј), 68.6 (C-5Ј), 69.5 (C-2), 72.7 (C-3), 74.2 (C-5), 78.4 (C-1),
(C-3), 75.1 (C-5), 79.9 (C-1), 95.9 (C-1Ј), 117.6 (aryl C-2, C-6), 95.4 (C-1Ј), 116.9 (aryl C-2, C-6), 129.5 (aryl C-3, C-5), 130.5 (aryl
130.3 (aryl C-3, C-5), 131.1 (aryl C-4), 154.9 (aryl C-1), 153.5 (C- C-4), 154.1 (aryl C-1), 152.5 (C-7), 169.1, 169.2, 169.5, 169.6, 169.6,
7), 169.9, 170.0, 170.3, 170.5, 170.6, 170.8 (CH3CO) ppm. MS 169.9 (CH3CO) ppm. MS (IS–): m/z = 922.5 [M – K]+. HRMS
(IS–): m/z = 864 [M – K]+. HRMS (ESI): calcd. for C34H42NO21S2
(ESI): calcd. for C36H44NO23S2 922.1751; found 922.1757.
864.1696; found 864.1703.
Typical Procedure for the De-O-acetylation of Glycosylated Glucos-
inalbins. Synthesis of 1 and 32–35: A catalytic amount of potassium
hydroxide was added to a solution of compound 27 (0.089 g,
0.098 mmol) in methanol (5 mL). After standing at room tempera-
ture for 4 h, the reaction mixture was neutralized by the addition
Per-O-acetylated 4Ј-O-(β-D-Glucopyranosyl) Glucosinalbin (28):
1
Colourless syrup (0.072 g, 49%). [α]D = +31 (c = 0.4, MeOH). H
NMR (250 MHz, [D6]DMSO): δ = 1.92, 1.93, 1.95, 1.96, 1.99, 2.00
(6 s, 24 H, CH3CO), 3.76–4.25 (m, 8 H, 5-H, 5Ј-H, 6-H, 6Ј-H,
CH2Ar), 4.78–5.07 (m, 4 H, 1-H, 2-H, 3-H, 4-H), 5.27–5.42 (m, 3 of Dowex H+ resin. After filtration, the solvent was evaporated in
H, 2Ј-H, 3Ј-H, 4Ј-H), 5.53 (d, J1Ј,2Ј = 7.9 Hz, 1 H, 1Ј-H), 6.97 (d, vacuo. Chromatographic purification of the residue on C-18 silica
Jvic = 8.5 Hz, 2 H, Har), 7.29 (d, Jvic = 8.5 Hz, 2 H, Har) ppm. 13C gel (eluent: water) followed by freeze-drying provided compound 1.
NMR (62.89 MHz, [D6]DMSO): δ = 21.1, 21.2, 21.3 (CH3CO),
4Ј-O-(α-L-Rhamnopyranosyl) Glucosinalbin (1): Amorphous solid
36.6 (CH2Ar), 62.5 (C-6, C-6Ј), 68.5, 68.9, 70.4, 71.5, 72.8, 73.6,
75.1 (C-2, C-3, C-4, C-5, C-2Ј, C-3Ј, C-4Ј, C-5Ј), 79.2 (C-1), 98.0
(C-1Ј), 117.3 (aryl C-2, C-6), 130.4 (aryl C-3, C-5), 131.2 (aryl C-
4), 153.4 (C-7), 156.2 (aryl C-1), 169.9, 170.0, 170.2, 170.4, 170.8
(CH3CO) ppm. MS (IS–): m/z = 923 [M – K]+. HRMS (ESI): calcd.
for C36H44NO23S2 922.1751; found 922.1764.
1
(0.060 g, quantitative yield). [α]D = –47 (c = 1.0, H2O). H NMR
(500 MHz, D2O): δ = 1.26 (d, J6Ј,5Ј = 5.8 Hz, 3 H, 6Ј-H), 3.26 (m,
1 H, 5-H), 3.32–3.48 (m, 3 H, 2-H, 3-H, 4-H), 3.55 (t, Jvic = 9.7 Hz,
1 H, 4Ј-H), 3.64–3.72 (m, 2 H, 6-H), 3.83 (m, 1 H, 5Ј-H), 4.03 (dd,
J2Ј,3Ј = 3.5 Hz, 1 H, 3Ј-H), 4.13 (s, 2 H, CH2Ar), 4.20 (dd, J1Ј,2Ј
=
1.9 Hz, 1 H, 2Ј-H), 4.74 (m, 1 H, 1-H), 5.58 (br. s, 1 H, 1Ј-H), 7.18
Per-O-acetylated 4Ј-O-(β-D-Galactopyranosyl) Glucosinalbin (29): (d, Jvic = 8.5 Hz, 2 H, 2-Har, 6-Har), 7.40 (d, Jvic = 8.0 Hz, 2 H, 3-
White amorphous solid (0.138 g, 76%); m.p. 162–164 °C. [α]D = –2
Har, 5-Har) ppm. 13C NMR (125.7 MHz, D2O): δ = 18.2 (C-6Ј),
39.0 (CH2Ar), 61.8 (C-6), 70.2 (C-4), 70.9 (C-5Ј), 71.5 (C-2Ј), 71.6
(c = 1.0, MeOH). 1H NMR (250 MHz, [D6]DMSO): δ = 1.92, 1.93,
1.96, 1.99, 2.02, 2.13 (7 s, 24 H, CH3CO), 3.76 (m, 1 H, 5-H), 3.89– (C-3Ј), 73.3 (C-2), 73.5 (C-4Ј), 78.5 (C-3), 81.3 (C-5), 82.9 (C-1),
4.08 (m, 6 H, 6-H, 6Ј-H, CH2Ar), 4.41 (m, 1 H, 5Ј-H), 4.77–4.94
(m, 2 H), 5.19–5.33 (m, 5 H), 5.43 (d, 1 H, 1-H), 6.96 (d, Jvic
99.6 (C-1Ј), 119.1 (aryl C-2, C-6), 130.9 (aryl C-3, C-5), 130.9 (aryl
C-4), 156.2 (aryl C-1), 164.2 (C-7) ppm. MS (IS–): m/z = 570.5
=
3662
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3657–3664

Synthesis of O-Glycosylated Derivatives of Glucosinalbin
[M – K]+. HRMS (ESI): calcd. for C20H28NO14S2 570.0957; found
570.0939.
MS (IS+): m/z = 626 [M + H]+, 648 [M + Na]+, 664 [M + K]+.
MS (IS–): m/z = 586.5 [M – K]+. HRMS (ESI): calcd. for
C20H28NO15S2 586.0906; found 586.0888.
4Ј-O-(β-D-Glucopyranosyl) Glucosinalbin (32): Amorphous solid
1
(0.097 g, quantitative yield). [α]D = –11 (c = 1.0, H2O). H NMR
(500 MHz, D2O): δ = 3.26 (m, 1 H, 5-H), 3.33–3.40 (m, 2 H, 2-H,
3-H), 3.44 (t, Jvic = 8.7 Hz, 1 H, 4-H), 3.54 (t, Jvic = 9.3 Hz, 1 H,
4Ј-H), 3.61 (t, Jvic = 7.7 Hz, 1 H, 2Ј-H), 3.64–3.68 (m, 4 H, 6-H,
3Ј-H, 5Ј-H), 3.79 (dd, Jgem = 12.4, Jvic = 5.4 Hz, 1 H, 6bЈ-H), 3.96
(d, Jgem = 12.4 Hz, 1 H, 6aЈ-H), 4.14 (s, 2 H, CH2Ar), 4.75 (d, Jvic
= 9.0 Hz, 1 H, 1-H), 5.15 (d, Jvic = 7.5 Hz, 1 H, 1Ј-H), 7.18 (d, Jvic
= 8.4 Hz, 2 H, 2-Har, 6-Har), 7.39 (d, Jvic = 8.4 Hz, 2 H, 3-Har, 5-
Har) ppm. 13C NMR (125.7 MHz, D2O): δ = 39.0 (CH2Ar), 61.5
(C-6), 61.9 (C-6Ј), 70.4 (C-4), 70.9 (C-4Ј), 73.3 (C-2), 74.4 (C-2Ј),
77.0 (C-3Ј), 77.5 (C-5Ј), 78.4 (C-3), 81.1 (C-5), 82.7 (C-1), 101.6
(C-1Ј), 118.5 (aryl C-2, C-6), 131.0 (aryl C-3, C-5), 131.1 (aryl C-
4), 157.4 (aryl C-1), 164.2 (C-7) ppm. MS (IS–): m/z = 586.5 [M –
K]+. HRMS (ESI): calcd. for C20H28NO15S2 586.0906; found
586.0895.
Acknowledgments
The authors thank the French Ministère de l’Enseignement Supéri-
eur et de la Recherche for a grant (D. G.). We also thank Dr. S.
Moutard and Dr. B. Perly for NMR spectroscopy.
[1] a) R. F. Mithen, M. Dekker, R. Verkerk, S. Rabot, I. T. John-
son, J. Sci. Food Agric. 2000, 80, 967–984; b) M. Traka, R.
Mithen, Phytochem. Rev. 2009, 8, 269–282.
[2] I. T. Johnson, Int. J. Vitam. Nutr. Res. 2002, 72, 26–31.
[3] J. W. Fahey, A. T. Zalcmann, P. Talalay, Phytochemistry 2001,
56, 5–51.
[4] J. T. A. Oliveira, S. B. Silveira, I. M. Vasconcelos, B. S. Cavada,
R. A. Moreira, J. Sci. Food Agric. 1999, 79, 815–820.
[5] R. N. Bennett, F. A. Mellon, N. Foidl, J. H. Pratt, M. S. Du-
pont, L. Perkins, P. A. Kroon, J. Agric. Food Chem. 2003, 51,
3546–3553.
[6] M. H. S. Mughal, P. S. Srivastava, M. Iqbal, J. Econ. Taxon.
Bot. 1999, 23, 47–61.
[7] a) A. Ndabigengesere, K. S. Narasiah, Water Res. 1998, 32,
781–791; b) T. Okuda, A. U. Baes, W. Nishijima, M. Okada,
Water Res. 2001, 35, 405–410.
[8] A. P. Guevara, C. Vargas, H. Sakurai, Y. Fujiwara, K. Hashim-
oto, T. Maoka, M. Kozuka, Y. Ito, H. Tokuda, H. Nishino,
Mutat. Res. 1999, 440, 181–188.
[9] S. R. Kurma, S. H. Mishra, Indian J. Nat. Prod. 1998, 14, 3–
10.
[10] S. R. Kurma, S. H. Mishra, Pharm. Biol. 1998, 36, 295–300.
[11] A. Kjaer, O. Malver, B. El-Menshawi, J. Reisch, Phytochemistry
1979, 18, 1485–1487.
4Ј-O-(β-D-Galactopyranosyl) Glucosinalbin (33): Amorphous solid
1
(0.097 g, quantitative yield). [α]D = –24 (c = 1.0, H2O). H NMR
(500 MHz, D2O): δ = 3.28 (m, 1 H, 5-H), 3.35–3.42 (m, 2 H, 2-H,
3-H), 3.45 (t, Jvic = 9.2 Hz, 1 H, 4-H), 3.69 (s, 2 H, 6-H), 3.83–3.87
(m, 3 H, 2Ј-H, 6Ј-H), 3.91 (m, 1 H, 5Ј-H), 4.06 (s, 1 H, 4Ј-H), 4.14–
4.19 (m, 3 H, 3Ј-H, CH2Ar), 4.77 (d, Jvic = 9.0 Hz, 1 H, 1-H), 5.10
(d, Jvic = 7.1 Hz, 1 H, 1Ј-H), 7.20 (d, Jvic = 8.0 Hz, 2 H, 2-Har, 6-
Har), 7.40 (d, Jvic = 8.0 Hz, 2 H, 3-Har, 5-Har) ppm. 13C NMR
(125.7 MHz, D2O): δ = 39.0 (CH2Ar), 61.8 (C-6), 62.3 (C-6Ј), 67.3,
70.0 (C-2Ј, C-4Ј), 70.2 (C-4), 73.3 (C-2), 74.0 (C-3Ј), 76.8 (C-5Ј),
78.4 (C-3), 81.3 (C-5), 82.8 (C-1), 102.2 (C-1Ј), 118.5 (aryl C-2, C-
6), 131.0 (aryl C-3, C-5), 157.5 (aryl C-1), 164.2 (C-7) ppm. MS
(IS–): m/z = 586. 5 [M – K]+ . HRMS (ESI): calcd. for
C20H28NO15S2 586.0906; found 586.0891.
[12] O. Olsen, H. Sorensen, Phytochemistry 1979, 18, 1547–1552.
[13] O. Olsen, K. W. Rasmussen, H. Sorensen, Phytochemistry 1981,
20, 1857–1861.
4Ј-O-(β-Cellobiosyl) Glucosinalbin (34): Amorphous solid (0.106 g,
quantitative yield). [α]D = –40 (c = 1.0, H2O). 1H NMR (500 MHz,
D2O): δ = 3.23 (m, 1 H, 5-H), 3.32–3.35 (m, 3 H, 2-H, 3-H, 2ЈЈ-
H), 3.39–3.45 (m, 2 H, 4-H, 4ЈЈ-H), 3.50–3.55 (m, 2 H, 3ЈЈ-H, 5ЈЈ-
H), 3.63 (m, 3 H, 6-H, 2Ј-H), 3.73–3.77 (m, 4 H, 3Ј-H, 4Ј-H, 5Ј-H,
6bЈЈ-H), 3.88 (dd, Jgem = 11.7, Jvic = 2.3 Hz, 1 H, 6bЈ-H), 3.93 (dd,
Jgem = 12.3, Jvic = 2.0 Hz, 1 H, 6aЈЈ-H), 4.00 (d, Jgem = 11.7 Hz, 1
H, 6aЈ-H), 4.11 (s, 2 H, CH2Ar), 4.55 (d, J1ЈЈ,2ЈЈ = 7.9 Hz, 1 H, 1ЈЈ-
H), 4.72 (m, 1 H, 1-H), 5.15 (d, J1Ј,2Ј = 7.9 Hz, 1 H, 1Ј-H), 7.16 (d,
Jvic = 8.7 Hz, 2 H, 2-Har, 6-Har), 7.40 (d, Jvic = 8.7 Hz, 2 H, 3-Har,
5-Har) ppm. 13C NMR (125.7 MHz, D2O): δ = 39.0 (CH2Ar), 61.3
(C-6Ј), 61.7 (C-6), 62.1 (C-6ЈЈ), 70.2 (C-4), 70.9 (C-4ЈЈ), 73.3 (C-2),
74.2 (C-2Ј), 74.7 (C-2ЈЈ), 75.6 (C-4Ј), 76.4 (C-3Ј), 77.0 (C-3ЈЈ), 77.5
(C-5ЈЈ), 78.4 (C-3), 79.8 (C-5Ј), 81.3 (C-5), 82.9 (C-1), 101.5 (C-1Ј),
104.1 (C-1ЈЈ), 118.6 (aryl C-2, C-6), 130.9 (aryl C-3, C-5), 131.2
(aryl C-4), 157.4 (aryl C-1), 164.2 (C-7) ppm. MS (IS–): m/z = 748.5
[M – K]+. HRMS (ESI): calcd. for C26H38NO20S2 748.1434; found
748.1415.
[14] U. Eilert, B. Wolters, A. Nahrstedt, Planta Med. 1981, 42, 55–
61.
[15] a) S. Faizi, B. S. Siddiqui, R. Saleem, S. Siddiqui, K. Aftab,
A. H. Gilani, J. Chem. Soc. Perkin Trans. 1 1992, 3237–3241;
b) S. Faizi, B. S. Siddiqui, R. Saleem, S. Siddiqui, K. Aftab,
A. H. Gilani, J. Chem. Soc. Perkin Trans. 1 1994, 3035–3040.
[16] a) S. Faizi, B. S. Siddiqui, R. Saleem, S. Siddiqui, K. Aftab,
A. H. Gilani, J. Nat. Prod. 1994, 57, 1256–1261; b) S. Faizi,
B. S. Siddiqui, R. Saleem, S. Siddiqui, K. Aftab, A. H. Gilani,
J. Nat. Prod. 1997, 60, 1317–1321.
[17] D. Brunelli, M. Tavecchio, C. Falcioni, R. Frapolli, E. Erba,
R. Iori, P. Rollin, J. Barillari, C. Manzotti, P. Morazzoni, M.
D’Incalci, Biochem. Pharmacol. 2010, 79, 1141–1148.
[18] A. Murakami, Y. Kitazono, S. Jiwajinda, K. Koshimizu, H.
Ohigashi, Planta Med. 1998, 64, 319–323.
[19] See, for example: D. A. Whiting, Nat. Prod. Rep. 2001, 18, 583–
606, and references cited therein.
[20] D. Gueyrard, J. Barillari, R. Iori, S. Palmieri, P. Rollin, Tetra-
hedron Lett. 2000, 41, 8307–8309.
4Ј-O-(α-D-Mannopyranosyl) Glucosinalbin (35): Amorphous solid
(0.076 g, quantitative yield). [α]D = –6 (c = 1.0, H2O). 1H NMR
(500 MHz, D2O): δ = 3.24 (m, 1 H, 5-H), 3.32 (m, 2 H, 2-H, 3-H),
3.41 (t, Jvic = 9.5 Hz, 1 H, 4-H), 3.65 (s, 2 H, 6-H), 3.73–3.81 (m,
4 H, 4Ј-H, 5Ј-H, 6Ј-H), 4.05 (dd, J = 3.2, J = 8.9 Hz, 1 H, 3Ј-H),
4.11 (s, 2 H, CH2Ar), 4.17 (d, J1Ј,2Ј = 0.9 Hz, 1 H, 2Ј-H), 4.70 (m,
1 H, 1-H), 5.62 (d, J1Ј,2Ј = 0.9 Hz, 1 H, 1Ј-H), 7.19 (d, Jvic = 8.6 Hz,
2 H, Har), 7.37 (d, Jvic = 8.6 Hz, 2 H, Har) ppm. 13C NMR
(125 MHz, D2O): δ = 39.0 (CH2Ar), 61.8 (C-6), 62.2 (C-6Ј), 68.1
(C-4Ј), 70.3 (C-4), 71.4 (C-2Ј), 71.9 (C-3Ј), 73.3 (C-2), 74.9 (C-5Ј),
78.5 (C-3), 81.4 (C-5), 82.9 (C-1), 99.9 (C-1Ј), 119.1 (aryl C-2, C-
6), 130.9 (aryl C-4, C-3, C-5), 157.4 (aryl C-1), 164.2 (C-7) ppm.
[21] N. B. Bashir, S. J. Phythian, A. J. Reason, S. M. Roberts, J.
Chem. Soc. Perkin Trans. 1 1995, 2203–2222.
[22] G. H. Veeneman, S. H. van Leeuwen, J. H. van Boom, Tetrahe-
dron Lett. 1990, 31, 1331–1334.
[23] M. Leuck, H. Kunz, Carbohydr. Res. 1998, 312, 33–44.
[24] C. B. Gairaud, G. R. Lappin, J. Org. Chem. 1953, 18, 1–3.
[25] a) H. R. Rackwitz, Carbohydr. Res. 1981, 88, 223–232; b) D.
Oulmi, P. Maillard, J. L. Guerquin-Kern, C. Huel, M. Momen-
teau, J. Org. Chem. 1995, 60, 1554–1564.
[26] T. P. Kogan, B. Dupré, H. Bui, K. L. McAbee, J. M. Kassir,
I. L. Scott, X. Hu, P. Vanderslice, P. J. Beck, R. A. F. Dixon, J.
Med. Chem. 1998, 41, 1099–1111.
Eur. J. Org. Chem. 2010, 3657–3664
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3663

D. Gueyrard, R. Iori, A. Tatibouët, P. Rollin
FULL PAPER
[27] a) G. Kumaran, G. H. Kulkarni, J. Org. Chem. 1997, 62, 1516–
1520; b) S. Cassel, B. Casenave, G. Déléris, L. Latxague, P.
Rollin, Tetrahedron 1998, 54, 8515–8524; c) D. Cerniauskaite,
E. Gallienne, H. Karciauskaite, A. S. F. Farinha, J. Rousseau,
S. Armand, A. Tatibouët, A. Sackus, P. Rollin, Tetrahedron
Lett. 2009, 50, 3302–3305.
[28] A. Bourderioux, M. Lefoix, D. Gueyrard, A. Tatibouët, S.
Cottaz, S. Arzt, W. P. Burmeister, P. Rollin, Org. Biomol. Chem.
2005, 3, 1872–1879.
[29] D. D. Perrin, W. L. F. Armarego, D. R. Perrin, Purification of
Laboratory Chemicals, Pergamon Press, Oxford, 1986.
Received: February 23, 2010
Published Online: May 19, 2010
3664
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 3657–3664