Glucosinolate synthesis: A hydroxamic acid approach

Article abstract of DOI:10.1002/ejoc.201001438

A new method for accessing the thiohydroximate function allows an alternative synthetic pathway to glucosinolates. O-Silylated hydroxamic acids were prepared and were then activated with triflic anhydride to generate transient nitrile oxides to be condens

Full text of DOI:10.1002/ejoc.201001438

FULL PAPER
DOI: 10.1002/ejoc.201001438
Glucosinolate Synthesis: a Hydroxamic Acid Approach
Deimante Cerniauskaite,[a,b] Jolanta Rousseau,[a] Algirdas Sackus,[b] Patrick Rollin,[a] and
Arnaud Tatibouët*[a]
Keywords: Lactones / Hydroxamic acids / Nitrile oxides / Thiohydroximates / Glucosinolates / Carbohydrates / Natural
products
A new method for accessing the thiohydroximate function
allows an alternative synthetic pathway to glucosinolates. O-
Silylated hydroxamic acids were prepared and were then ac-
tivated with triflic anhydride to generate transient nitrile ox-
ides to be condensed with ethanethiol. The procedure was
further applied to the synthesis of naturally occurring glucos-
inolates.
to date been the most intensively studied for its potent bio-
activity, especially as a chemopreventive anticancer agent.[6]
Despite the very large number of known GL-containing
plant species, accessing these compounds from appropriate
vegetable sources through extractive processes is not
straightforward.[7] Many variations can be observed, de-
pending on species, parts of the plant, age of the plant,
growing conditions, stress factors, etc. Only a limited
number of “specialist” plants can deliver one specific gluco-
sinolate in large amounts,[8] so the synthetic approach is a
key way to prepare either rare or artificial GLs for bio-
logical studies (Figure 2).[9]
In nearly all synthetic methods developed over the years,
the key step has been the stereospecific formation of a
thiohydroximate function, usually resulting from a 1,3-ad-
dition of a thiol to a transient nitrile oxide.[9b] Because they
are generally highly unstable species, nitrile oxides have to
be generated in situ through base-induced conversion of hy-
droximoyl chlorides. Another approach based on electro-
philic activation of primary nitroalkyl derivatives was pion-
eered by Mukaiyama and further extended by others;[10]
that method, however, cannot be applied for a thiol ad-
dition. Our attention was attracted by another dehydrative
method, developed by Carreira and involving O-silylated
hydroxamic acids to prepare isoxazoline cycloadducts.[11] In
this paper we report the use of transient O-activated NO-
silylated hydroximoyl derivatives as electrophilic acceptors
for the production of thiohydroximates.
Introduction
Glucosinolates (GLs) are natural chemical tags of the bo-
tanical order Brassicales.[1] These secondary metabolites are
naturally occurring thiosaccharide compounds found in all
16 families of this order. All known GLs (ca. 120) display
remarkable structural homogeneity, being based on a hy-
drophilic β-d-glucopyrano unit bearing an O-sulfated an-
omeric (Z)-thiohydroximate function connected to a rather
hydrophobic side chain R (Figure 1). Depending on the
plant species, the constitution of R is the sole structural
variant, in which diversified aliphatic, arylaliphatic or het-
erocyclic arrangements can be found. GLs are part of an
essential defence mechanism of the plant, and they act as
proactive metabolites.[2] In plants, they are closely associ-
ated with an atypical glucohydrolase called myrosinase
(E.C. 3.2.1.147), which is able to convert GLs, through the
release of d-glucose and sulfate ion, into various products
(Figure 1), depending on the aglycon constitution.[3] How-
ever, the products generally formed are isothiocyanates
(ITCs), strong electrophiles known for their marked bio-
logical activities[4] and closely connected with human nu-
trition and health.[5] Of the natural ITCs, sulforaphane has
Figure 1. Enzymatic degradation of GLs to isothiocyanates.
Results and Discussion
Hydroxamic acids were prepared by use of hydroxyl-
amine either in lactone opening or in acyl chloride substitu-
tion.[12] The synthetic sequence was first explored for a
model compound obtained from γ-valerolactone
(Scheme 1).
[a] Institut de Chimie Organique et Analytique, Université
d’Orléans,
B. P. 6759, 45067 Orléans Cedex 2, France
E-mail: arnaud.tatibouet@univ-orleans.fr
[b] Kaunas University of Technology,
Radvilenu st.19, 50270 Kaunas, Lithuania
Eur. J. Org. Chem. 2011, 2293–2300
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D. Cerniauskaite, J. Rousseau, A. Sackus, P. Rollin, A. Tatibouët
FULL PAPER
Figure 2. Methods for formation of nitrile oxides.
Scheme 1. Model synthetic sequence for a thiohydroximate.
Under basic conditions, γ-valerolactone (1a) was con- group proved satisfactory in the next two-step sequence, in-
densed with excess hydroxylamine in MeOH to produce the volving hydroximoyl triflate activation followed by ethane-
hydroxamic acid 2a in 93% yield. During silica gel column thiol condensation to afford the thiohydroximate 4a
purification, some spontaneous back-cyclization to the lac- (Table 1).
tone was observed. Nonetheless, the subsequent bis-O-
The activation of the bis-O-silylated derivative 3a was
silylation step was performed to afford a 61% yield of the performed with a dichloromethane solution of triflic anhy-
protected hydroxamic acid. Despite Carreira’s remark about dride (1 m). The study (Table 1) was mainly focused on two
its lability,[11] in our hands the tert-butyldimethylsilyl (TBS) reaction parameters. Entries 1–4 show the results obtained
Table 1. Optimization of the two-step synthesis of the ethylthiohydroxymate 4a.
Entry
First step
Base, equiv.
Second step
Base, equiv.
Yield [%]
Tf2O[a] [equiv.]
T [h]
EtSH[a] [equiv.]
T [h]
1
2
3
4
5
6
7
8
9
1.1
1.1
1.1
1.5
1.2
1.2
1.2
Et3N, 3
Et3N, 3
Et3N, 3
1
1
1
1
1
1
1
1
1
2
5
Et3N, 0
Et3N, 3
Et3N, 2
15
36
15
15
15
15
15
15
15
20
50
62
34
10
10
10
10
10
10
10
Et3N, 3
Et3N, 2
[c]
lutidine, 3
DMAP, 3
DIPEA, 3
DBU, 3
lutidine, 2
DMAP, 2
DIPEA, 2
DBU, 2
–
–
[c]
42
[d]
1.2
–
1.2[b]
Et3N, 3
Et3N, 2
80
[a] Solution in DCM (1 m). [b] Neat. [c] No reaction. [d] Degradations.
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Glucosinolate Synthesis: a Hydroxamic Acid Approach
with variation of the amounts of ethanethiol and Et3N; the protected hydroxamic acids being obtained in ca. 48% yield
best yield (Entry 3) was achieved by use of a large excess of in both cases. However, this modest yield increase was
thiol (10 equiv.), whereas no improvement was observed on counterbalanced by additional difficulties in purification.
increasing the added volume of triflic anhydride solution
Table 2. Yields for the synthesis of the thiohydroximates 4 from the
(Entry 4). Entries 5–9 reveal the dramatic influence of the
base on the reaction with the base/thiol (2:10) ratio kept
lactones 1.
Entry
1
2
3
4
Overall yield
constant; of the different bases tested, triethylamine (En-
try 4) proved far more efficient than DIPEA (Entry 7), and
a further yield increase to 80% (Entry 9) could be achieved
by use of neat triflic anhydride in the first step. This last
protocol was therefore used throughout the study.
Application of the established three-step procedure to the
starting materials 1b–g afforded the thiohydroximates 4 in
satisfactory overall yields (Scheme 2).
1
2
3
4
5
6
7
a
b
c
d
e
f
93%
91%
98%
90%
99%
99%
61%
49%
57%
49%
43%
58%
–
80%
78%
82%
77%
61%
88%
–
45%
35%
46%
34%
26%
50.5%
–
[a]
g
–
[a] Not isolated.
The subsequent two-step introduction of the ethylsul-
fanyl moiety was then applied. In all cases, the expected S-
ethyl thiohydroximate 4 was formed in fairly good yields.
The simple thiohydroximates 4a–4d were obtained in ca.
80% yields, whereas for the arylalkyl derivative 4f an even
more efficient conversion (88% yield) was observed. This
compares favourably with previous results from our labora-
tory, in which the thiohydroximate 4f was prepared from a
nitrovinyl precursor in only 47% yield.[13] A less efficient
conversion (61% yield) was observed with the phenol-de-
rived compound 4e. This reduction in yield could again be
explained by the sensitivity of an O-silylated phenol group
under basic conditions.
A three-step method to prepare thiohydroximates from
simple lactones or phenylacetyl chloride in 26–50% overall
yields having been developed, our next target was to explore
its potential in glucosinolate synthesis. For this, the bis-O-
silylated hydroxamic acids 3a, 3c, 3e and 3f were selected
as model substrates.
Through application of the previously established condi-
tions, the protected hydroxamic acids were treated with
2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranose (5) to af-
ford the corresponding glucopyranosyl thiohydroximates 6
with complete (Z) stereocontrol (Scheme 3).
Use of a stoichiometric amount of the thioglucose 5 in
the coupling process with the protected hydroxamic acids 3
proved efficient enough to provide good yields over the two-
step sequence. The aliphatic thiohydroximates 6a and 6c
Scheme 2. Synthesis of the thiohydroximates 4.
The hydroxylaminolysis of lactones (Table 2, Entries 1–5 were produced in 81% and 75% yields, respectively, with 6a
and 7) appeared to be a very efficient process for the pro- being obtained in the form of a 3:2 mixture of epimers that
duction of hydroxamic acids, albeit with the exception of d- were not separated. The arylaliphatic thiohydroximates 6e
pantolactone (1g); this α-hydroxylactone did in fact react and 6f were also obtained in preparative yields (62 and
well to form (as detected by TLC) the corresponding hy- 85%, respectively). The lower isolated yield observed for the
droxamic acid, but silica gel column purification caused thiohydroximate 6e is ascribable to the formation of the side
spontaneous back-cyclization to 1g. The subsequent silyl product 7, resulting either from the persistence of a TBS
protection step to produce the bis-O-silylated hydroxamic group or from a trans-O-silylation occurring during the re-
acids 3 proved more complex, with moderate (43% 3e, En- action.
try 5) to reasonable (61% 3a, Entry 1) yields. This limita-
A literature survey[9b] made it clear that our approach to
tion in yields could be attributed to the lability of the N- the formation of thiohydroximates compares favourably in
silyloxycarboxamide group. Different protecting groups terms of yields and convenience. The preparation of the
were therefore tested on the most disappointing coumar- thiohydroximate 6f from 2-nitrostyrene by our previously
anone-derived substrate. Both tert-butyldiphenylsilyl and reported procedure,[12b,13] for example, resulted in a 77%
pivaloyl groups were tested on 2e, with the resulting bis-O- yield.
Eur. J. Org. Chem. 2011, 2293–2300
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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D. Cerniauskaite, J. Rousseau, A. Sackus, P. Rollin, A. Tatibouët
FULL PAPER
Scheme 3. Synthesis of the glucopyranosyl thiohydroximates.
The final steps to produce the glucosinolates involved O- step (potassium methoxide in methanol, 1 m) to afford (i) a
sulfation of the NOH moiety followed by cleavage of the 79% yield of 4-hydroxybutyl glucosinolate (9), which has
acetates and silyl ethers.[12b] This was demonstrated with been identified in Capparis flexuosa and Arabidopsis thali-
the selected thiohydroximates 6c and 6e (Scheme 4), with ana[17] and (ii) a 88% yield of 2-hydroxybenzyl glucosinol-
compound 6a not being considered because it was an epi- ate (10), present in several Reseda sp.[18]
meric mixture, whereas 6f was not further explored because
its conversion into glucotropaeolin had been described pre-
viously.[14] NO-Sulfation of 6c and 6e in ca. 65% yields was
Conclusions
achieved through the use of pyridine/sulfur trioxide com-
We have introduced a new approach to the synthesis of
plex in CH2Cl2. All protecting groups were removed in one
alkyl and arylalkyl thiohydroximates. Hydroxamic acids,
generally obtained from lactones, were O-silylated prior to
triflate activation to generate transient nitrile oxides, which
readily underwent 1,3-addition of thiols. This was success-
fully extended to the synthesis of the naturally occurring
glucosinolates 9 and 10 and also provided a formal synthe-
sis of glucotropaeolin, the ISO standard for glucosinolate
analysis.
Experimental Section
General: Reactions under anhydrous conditions were performed
under argon in pre-dried flasks, with anhydrous solvents (distilled
when necessary as described in D. D. Perrin, W. L. F. Armarego
and D. R. Perrin, Purification of Laboratory Chemicals, Pergamon,
Oxford, 1986). All chemicals obtained from commercial suppliers
were used without further purification. TLC (precoated alumin-
ium-backed plates, Merck Kieselgel 60F254) were visualized with
UV light (254 nm) and by charring after exposure to a solution of
H2SO4 in ethanol (5%). Flash column chromatography was per-
formed with silica gel (36–63 mesh, E. Merck). Melting points [°C]
were obtained with a Büchi 510 apparatus and are uncorrected.
Optical rotations were measured at 20 °C with a Perkin–Elmer 341
1
polarimeter with a path length of 1 dm. H and 13C NMR spectra
Scheme 4. Synthesis of naturally occurring glucosinolates.
2296
were recorded with a 400 MHz Bruker Avance 2 spectrometer.
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Eur. J. Org. Chem. 2011, 2293–2300

Glucosinolate Synthesis: a Hydroxamic Acid Approach
Chemical shifts are expressed in parts per million (ppm) downfield
from TMS as internal standard. Coupling patterns for 1H NMR
are designated as s = singlet, d = doublet, t = triplet, q = quartet,
m = multiplet, and coupling constants are given in Hz. NMR peak
assignments were established by use of NOESY, COSY, HSQC and
HMBC methods for all reported compounds. IR spectra were mea-
sured with a Thermo Scientific Nicolet iS10 FT-IR spectrophotom-
eter. IR absorption frequencies are given in cm–1. Mass spectra
were recorded with an API-300 spectrometer [Ionspray® (IS)
mode]. High-resolution mass spectra (HRMS) were recorded with
a MicrOTOF-QII spectrometer in the electrospray ionisation (ESI)
mode.
N-Hydroxy-2-phenylacetamide (2f):[16] White solid (0.228 g, 100%),
m.p. 143–145 °C (petroleum ether/EtOAc), Rf = 0.28 (EtOAc/
MeOH, 9:1). 1H NMR ([D6]DMSO): δ = 10.65 (s, 1 H, N–OH),
8.82 (s, 1 H, NH), 7.31–7.20 (m, 5 H, Ar-H), 3.28 (s, 2 H, CH2)
ppm. 13C NMR ([D6]DMSO): δ = 166.9 (C=O), 136.0 (aryl C-1),
128.8, 128.1 (aryl C-2, C-3, C-5, C-6), 126.3 (aryl C-4), 39.3 (CH2)
ppm. IR (KBr): ν = 3175 (NH, OH), 1629 (C=O) cm–1. MS (IS+):
˜
m/z = 152 [M + H]+.
Typical Procedure for the Per-O-silylation of the Hydroxamic Acids
3a–f: Imidazole (1.2 equiv. per hydroxy group) and then tert-butyl-
dimethylsilyl chloride (1.2 equiv. per hydroxy group) were added
under argon to an ice-cold solution of the hydroxamic acid (1 m,
1 equiv.) in dry DMF. The mixture was allowed to warm to room
temperature and then, after 16 h of stirring, diluted with ethyl acet-
ate. The resulting organic phase was washed with water (4ϫ) and
then brine and dried with MgSO4. After evaporation of the solvent,
the residue was purified by flash chromatography (eluent: petro-
leum ether/EtOAc, 19:1).
Typical Procedure for the Synthesis of the Hydroxamic Acids 2a–
f:[15a] KOH (5 equiv.) was added to a cooled (0 °C) solution of hy-
droxylamine hydrochloride (1 m, 5 equiv.) in MeOH. After 10 min,
the resulting suspension was filtered off, and the lactone or phen-
ylacetyl chloride (1 equiv.) was then added to the solution. After
the mixture had been stirred at room temperature overnight, the
solvent was evaporated under reduced pressure, and the residue was
purified by flash column chromatography (eluent: EtOAc/MeOH).
N,4-Bis(tert-butyldimethylsilyloxy)pentanamide (3a): Colourless oil
(2.05 g, 61%), Rf = 0.24 (petroleum ether/EtOAc, 9:1). 1H NMR
(CDCl3): δ = 7.84 (s, 1 H, NH), 3.87 (m, 1 H, 4-H), 2.35–2.13 (m,
2 H, 2-H), 2.27–2.17 (m, 1 H, 3a-H), 1.84–1.65 (m, 1 H, 3b-H),
1.14 (d, Jvic = 6.0 Hz, 3 H, CH3), 0.96 (s, 9 H, tBuSiON), 0.88 (s,
9 H, tBuSiO), 0.18 (s, 6 H, Me2SiON), 0.05 (s, 6 H, Me2SiO) ppm.
13C NMR (CDCl3): δ = 160.4 (C=O), 67.8 (C-4), 34.5 (C-3), 29.4
(C-2), 25.9, 25.8 (Me3CSi), 23.6 (C-5), 18.3 (Cq, tBuSi), –4.3 (Me2-
N,4-Dihydroxypentanamide (2a):[15b] Colourless oil (0.65 g, 93%),
1
Rf = 0.26 (EtOAc/MeOH, 9:1). H NMR ([D6]DMSO): δ = 10.42
(s, 1 H, NOH), 8.63 (s, 1 H, NH), 4.45 (s, 1 H, OH), 3.54 (m, 1 H,
4-H), 2.06–1.92 (m, 2 H, 2-H), 1.57–1.44 (m, 2 H, 3-H), 1.02 (d,
Jvic = 6.0 Hz, 3 H, CH3) ppm. 13C NMR ([D6]DMSO): δ = 169.4
(C=O), 65.3 (C-4), 34.7 (C-3), 28.9 (C-2), 23.4 (C-5) ppm. IR (film):
ν = 3195 (NH, OH), 1636 (C=O) cm–1. MS (IS+): m/z = 134 [M +
SiO), –4.7 (Me SiON) ppm. IR (film): ν = 3180 (NH), 1654 (C=O)
˜
2
˜
cm–1. MS (IS+): m/z = 362 [M + H]+. HRMS (ESI): calcd. for
H]+, 156 [M + Na]+, 172 [M + K]+.
C17H40NO3Si2 362.2547; found 362.2558.
N,4-Dihydroxybutanamide (2b):[15a] Colourless oil (1.4 g, 91%), Rf
N,4-Bis(tert-butyldimethylsilyloxy)butanamide (3b): Colourless so-
lid (1.71 g, 49%), m.p. 45–47 °C (petroleum ether/EtOAc), Rf =
1
= 0.31 (EtOAc/MeOH, 9:1). H NMR ([D6]DMSO): δ = 10.33 (s,
1 H, NOH), 8.58 (s, 1 H, NH), 4.46 (s, 1 H, OH), 3.36 (t, J4,3
=
1
0.25 (petroleum ether/EtOAc, 9:1). H NMR (CDCl3): δ = 8.10 (s,
6.4 Hz, 2 H, 4-H), 1.98 (t, J2,3 = 7.6 Hz, 2 H, 2-H), 1.61 (m, 2 H,
1 H, NH), 3.66 (t, J4,3 = 6.0 Hz, 2 H, 4-H), 2.33–2.16 (m, 2 H, 2-
H), 1.83 (m, J3,2 = 6.8 Hz, 2 H, 3-H), 0.95 (s, 9 H, tBuSiON), 0.89
(s, 9 H, tBuSiO), 0.18 (s, 6 H, Me2SiON), 0.05 (s, 6 H, Me2SiO)
ppm. 13C NMR (CDCl3): δ = 162.3 (C=O), 62.2 (C-4), 30.2 (C-2),
28.1 (C-3), 25.9, 25.8 (Me3CSi), 18.3 (Cq, tBuSi), –5.4, –5.7 (Me2-
3-H) ppm. 13C NMR ([D6]DMSO): δ = 169.2 (C=O), 60.2 (C-4),
29.0 (C-2), 28.5 (C-3) ppm. IR (film): ν = 3190 (NH, OH), 1632
˜
(C=O) cm–1. MS (IS+): m/z = 120 [M + H]+.
N,5-Dihydroxypentanamide (2c):[15a] White solid (0.26 g, 98%), m.p.
91–93 °C (AcOEt), Rf = 0.35 (EtOAc/MeOH, 9:1). 1H NMR ([D6]-
DMSO): δ = 10.33 (s, 1 H, NOH), 8.60 (s, 1 H, NH), 4.37 (s, 1 H,
OH), 3.36 (t, J5,4 = 6.4 Hz, 2 H, 5-H), 1.93 (t, J2,3 = 7.2 Hz, 2 H,
2-H), 1.50 (qt, J3,4 = 6.0 Hz, 2 H, 3-H), 1.37 (qt, 2 H, 4-H) ppm.
13C NMR ([D6]DMSO): δ = 169.1 (C=O), 60.3 (C-5), 32.0 (C-2,
SiO) ppm. IR (KBr): ν = 1659 (C=O) cm–1. MS (IS+): m/z = 348
˜
[M + H]+. HRMS (ESI): calcd. for C16H38NO3Si2 348.2390; found
348.2398.
N,5-Bis(tert-butyldimethylsilyloxy)pentanamide (3c): Colourless so-
lid (0.268 g, 57%), m.p. 62–64 °C (petroleum ether/EtOAc), Rf =
C-4), 21.7 (C-3) ppm. IR (KBr): ν = 3186 (NH, OH), 1629 (C=O)
˜
1
0.26 (petroleum ether/EtOAc, 9:1). H NMR (CDCl3): δ = 7.89 (s,
cm–1. MS (IS+): m/z = 134 [M + H]+, 156 [M + Na]+.
1 H, NH), 3.62 (t, J5,4 = 6.4 Hz, 2 H, 5-H), 2.23–2.14 (m, 2 H, 2-
H), 1.70 (qt, J3,2 = J3,4 = 7.2 Hz, 2 H, 3-H), 1.55 (qt, 2 H, 4-H),
0.95 (s, 9 H, tBuSiON), 0.88 (s, 9 H, tBuSiO), 0.18 (s, 6 H, Me2-
SiON), 0.04 (s, 6 H, Me2SiO) ppm. 13C NMR (CDCl3): δ = 162.4
(C=O), 62.9 (C-5), 33.1 (C-2), 32.0 (C-4), 25.9, 25.8 (Me3CSi), 21.9
N,6-Dihydroxyhexanamide (2d):[15a] Colourless oil (0.72 g, 90%), Rf
1
= 0.38 (EtOAc/MeOH, 9:1). H NMR ([D6]DMSO): δ = 10.32 (s,
1 H, NOH), 8.65 (s, 1 H, NH), 4.34 (s, 1 H, OH), 3.37 (m, 2 H, 6-
H), 1.93 (t, J2,3 = 7.6 Hz, 2 H, 2-H), 1.47 (m, J3,4 = 7.2 Hz, 2 H,
3-H), 1.39 (m, J5,6 = 6.8, J5,4 = 7.2 Hz, 2 H, 5-H), 1.28–1.20 (m, 2
H, 4-H) ppm. 13C NMR ([D6]DMSO): δ = 169.0 (C=O), 60.3 (C-
(C-3), 18.3 (C , tBuSi), –5.3, –5.7 (Me SiO) ppm. IR (KBr): ν =
˜
q
2
1651 (C=O) cm–1. MS (IS+): m/z = 362 [M + H]+. HRMS (ESI):
6), 32.3 (C-2, C-5), 25.1 (C-3, C-4) ppm. IR (film): ν = 3191 (NH,
˜
calcd. for C17H40NO3Si2 362.2547; found 362.2537.
OH), 1638 (C=O) cm–1. MS (IS+): m/z = 148 [M + H]+.
N,6-Bis(tert-butyldimethylsilyloxy)hexanamide (3d): Yellowish oil
(0.643 g, 49%), Rf = 0.27 (petroleum ether/EtOAc, 9:1). H NMR
N-Hydroxy-2-(2-hydroxyphenyl)acetamide (2e):[15c] Yellow solid
1
(0.125 g, 99%), m.p. 88–90 °C (AcOEt), Rf = 0.24 (EtOAc/MeOH, (CDCl3): δ = 7.71 (s, 1 H, NH), 3.59 (t, J6,5 = 6.4 Hz, 2 H, 6-H),
1
9:1). H NMR ([D6]DMSO): δ = 10.60 (s, 1 H, NOH), 9.63 (s, 1
2.22–2.09 (m, 2 H, 2-H), 1.65 (m, J3,2 = J3,4 = 7.6 Hz, 2 H, 3-H),
H, OH), 8.85 (s, 1 H, NH), 7.08 (br. d, J6,5 = 8.0 Hz, 1 H, 6-H), 1.52 (m, J5,4 = 7.6 Hz, 2 H, 5-H), 1.40–1.32 (m, 2 H, 4-H), 0.96 (s,
7.04 (dt, 1 H, 4-H), 6.78 (br. d, J3,4 = 8.0 Hz, 1 H, 3-H), 6.73 (dt,
9 H, tBuSiON), 0.88 (s, 9 H, tBuSiO), 0.18 (s, 6 H, Me2SiON), 0.03
J5,3 = 0.8, Jvic = 7.2 Hz, 1 H, 5-H), 3.27 (s, 2 H, CH2) ppm. 13C (s, 6 H, Me2SiO) ppm. 13C NMR (CDCl3): δ = 171.8 (C=O), 63.0
NMR ([D6]DMSO): δ = 167.7 (C=O), 155.3 (C-2), 130.5 (C-6), (C-6), 32.5 (C-2, C-5), 26.0, 25.8 (Me3CSi), 25.5 (C-3, C-4), 18.3
127.6 (C-4), 122.1 (C-1), 118.8 (C-5), 115.1 (C-3), 34.0 (CH2) ppm.
(C , tBuSi), –5.3, –5.7 (Me SiO) ppm. IR (film): ν = 1659 (C=O)
˜
q 2
IR (KBr): ν = 3163 (NH, OH), 1649 (C=O) cm–1. MS (IS+): m/z
cm–1. MS (IS+): m/z = 376 [M + H]+. HRMS (ESI): calcd. for
˜
= 168 [M + H]+, 190 [M + Na]+.
C12H28NO3Si [M – TBDMS + H]+ 262.1838; found 262.1846.
Eur. J. Org. Chem. 2011, 2293–2300
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2297

D. Cerniauskaite, J. Rousseau, A. Sackus, P. Rollin, A. Tatibouët
FULL PAPER
N-(tert-Butyldimethylsilyloxy)-2-(2-tert-butyldimethylsilyloxy-
phenyl)acetamide (3e): Yellow solid (0.406 g, 43%), m.p. 105–
leum ether/EtOAc), Rf = 0.16 (petroleum ether/EtOAc, 9:1). 1H
NMR (CDCl3): δ = 8.64 (s, 1 H, NOH), 3.62 (t, J5,4 = 6.0 Hz, 2
107 °C (petroleum ether/EtOAc), Rf = 0.41 (petroleum ether/
EtOAc, 9:1). H NMR (CDCl3): δ = 8.00 (s, 1 H, NH), 7.23 (dd, 7.2 Hz, 2 H, 2-H), 1.71–1.64 (m, 2 H, 3-H), 1.60–1.54 (m, 2 H, 4-
J6,4 = 1.6, J6,5 = 7.6 Hz, 1 H, 6-H), 7.16 (dt, J4,3 = J4,5 = 7.6 Hz, 1 H), 1.31 (t, 3 H, SCH2CH3), 0.88 (s, 9 H, tBuSiO), 0.04 (s, 6 H,
H, 5-H), 2.88 (q, Jvic = 7.6 Hz, 2 H, SCH2CH3), 2.45 (t, J2,3 =
1
H, 4-H), 6.93 (dt, J5,3 = 0.8 Hz, 1 H, 5-H), 6.85 (dd, 1 H, 3-H),
3.52 (s, 2 H, CH2), 1.02 (s, 9 H, tBuSiOAr), 0.88 (s, 9 H, tBuSiON),
0.26 (s, 6 H, Me2SiOAr), 0.10 (s, 6 H, Me2SiON) ppm. 13C NMR
(CDCl3): δ = 169.2 (C=O), 153.1 (C-2), 131.2 (C-6), 128.6 (C-4),
125.1 (C-1), 122.0 (C-5), 119.0 (C-3), 36.5 (CH2), 25.8, 25.7
(Me3CSi), 18.3 (Cq, tBuSi), –4.1 (Me2SiOAr), –5.8 (Me2SiON)
Me2SiO) ppm. 13C NMR (CDCl3): δ = 156.0 (C=N), 62.6 (C-5),
32.4 (C-2), 32.1 (C-4), 25.9 (Me3CSi), 23.9 (C-3), 23.8 (SCH2CH3),
18.3 (Cq, tBuSi), 14.9 (SCH2CH3), –5.3 (Me2SiO) ppm. MS (IS+):
m/z = 292 [M + H]+. HRMS (ESI): calcd. for C13H30NO2SSi
292.1767; found 292.1755.
S-Ethyl
(Z)-6-(tert-Butyldimethylsilyloxy)hexanethiohydroximate
ppm. IR (KBr): ν = 3145 (NH), 1646 (C=O) cm–1. MS (IS+): m/z
˜
(4d): White solid (0.425 g, 1.39 mmol, 77%), m.p. 36–38 °C (petro-
leum ether/EtOAc), Rf = 0.16 (petroleum ether/EtOAc, 9:1). 1H
NMR (CDCl3): δ = 8.72 (s, 1 H, NOH), 3.60 (t, J6,5 = 6.4 Hz, 1
H, 6-H), 2.87 (q, J = 7.2 Hz, 2 H, SCH2CH3), 2.43 (t, J2,3 = 7.6 Hz,
2 H, 2-H), 1.63 (qt, J3,4 = 7.6 Hz, 2 H, 3-H), 1.53 (qt, J5,4 = 6.8 Hz,
2 H, 5-H), 1.43–1.37 (m, 2 H, 4-H), 1.31 (t, 3 H, SCH2CH3), 0.88
(s, 9 H, tBuSiO), 0.04 (s, 6 H, Me2SiO) ppm. 13C NMR (CDCl3):
= 396 [M + H]+. HRMS (ESI): calcd. for C20H38NO3Si2 396.2390;
found 396.2390.
N-(tert-Butyldimethylsilyloxy)-2-phenylacetamide (3f): Yellow solid
(0.28 g, 58%), m.p. 118–120 °C (petroleum ether/EtOAc), Rf = 0.38
(petroleum ether/EtOAc, 9:1). 1H NMR (CDCl3): δ = 7.69 (s, 1 H,
NH), 7.26–7.16 (m, 5 H, Ar-H), 3.42 (m, 2 H, CH2), 0.82 (s, 9 H,
tBuSiON), 0.04 (s, 6 H, Me2SiON) ppm. 13C NMR (CDCl3): δ = δ = 156.0 (C=N), 63.0 (C-6), 32.6 (C-2, C-5), 27.3 (C-3), 26.0
169.0 (C=O), 133.9 (aryl C-1), 129.2, 128.9 (aryl C-2, C-3, C-5, C- (Me3CSi), 25.3 (C-4), 23.8 (SCH2CH3), 18.3 (Cq, tBuSi), 14.9
6), 127.4 (aryl C-4) 41.1 (CH2), 25.8 (Me3CSi), 18.1 (Cq, tBuSi),
(SCH2CH3), –5.3 (Me2SiO) ppm. MS (IS+): m/z = 306 [M + H]+.
HRMS (ESI): calcd. for C14H32NO2SSi 306.1923; found 306.1922.
–5.8 (Me SiON) ppm. IR (KBr): ν = 1652 (C=O) cm–1. MS (IS+):
˜
2
m/z = 266 [M + H]+. HRMS (ESI): calcd. for C14H24NO2Si
S-Ethyl (Z)-2-[2-(tert-Butyldimethylsilyloxy)phenyl]ethanethiohyd-
roximate (4e): Yellow solid (0.075 g, 0.23 mmol, 61%), m.p. 97–
266.1576; found 266.1584.
Typical Procedure for the Two-Step Synthesis of the Thiohydroxim-
ates 4a–f: Triflic anhydride (1.2 equiv.) was added dropwise to a
cooled (–78 °C) dichloromethane solution (0.05 m) of one of the O-
silylated derivatives 3a–f (1 equiv.), containing Et3N (3.3 equiv.).
The mixture was allowed to warm to 0 °C over 1 h, and ethanethiol
(10 equiv.) and Et3N (2 equiv.) were then added. After 15 h of stir-
ring at room temperature, the reaction was quenched by addition
of ice/water and the mixture extracted with dichloromethane (3ϫ).
The collected organic phase was washed with brine and then dried
with MgSO4. After evaporation of the solvent, the residue was
purified by flash chromatography (eluent: petroleum ether/EtOAc,
9:1).
99 °C (petroleum ether/EtOAc), Rf = 0.29 (petroleum ether/EtOAc,
1
9:1). H NMR (CDCl3): δ = 7.48 (s, 1 H, NOH), 7.24 (dd, J6,4
=
2.0, J6,5 = 8.0 Hz, 1 H, 6-H), 7.14 (dt, J4,3 = J4,5 = 8.0 Hz, 1 H, 4-
H), 6.93 (dt, J5,3 = 1.2 Hz, 1 H, 5-H), 6.81 (dd, 1 H, 3-H), 3.80 (s,
2 H, CH2), 2.70 (q, J = 7.2 Hz, 2 H, SCH2CH3), 1.19 (t, 3 H,
SCH2CH3), 1.02 (s, 9 H, tBuSiO), 0.24 (s, 6 H, Me2SiO) ppm. 13C
NMR (CDCl3): δ = 155.7 (C=N), 153.2 (C-2aryl), 129.3 (C-6aryl),
127.9 (C-4aryl), 126.8 (C-1aryl), 121.4 (C-5aryl), 118.4 (C-3aryl), 32.7
(CH2), 25.8 (Me3CSi), 23.4 (SCH2CH3), 18.2 (Cq, tBuSi), 14.7
(SCH2CH3), –4.2 (Me2SiO) ppm. MS (IS+): m/z = 326 [M + H]+.
HRMS (ESI): calcd. for C16H28NO2SSi 326.1610; found 326.1597.
S-Ethyl (Z)-2-Phenylethanethiohydroximate (4f):[13] White solid
S-Ethyl (Z)-4-(tert-Butyldimethylsilyloxy)pentanethiohydroximate (0.129 g, 0.66 mmol, 88%), m.p. 91–93 °C (petroleum ether/
(4a): Yellow solid (0.5 g, 1.72 mmol, 80%), m.p. 74–76 °C (petro-
EtOAc), Rf = 0.18 (petroleum ether/EtOAc, 9:1).
leum ether/EtOAc), Rf = 0.16 (petroleum ether/EtOAc, 9:1). 1H
Typical Procedure for the Two-Step Synthesis of the Glucosyl
Thiohydroximates 6a–f: Triflic anhydride (1.2 equiv.) was added
dropwise to a cooled (–78 °C) dichloromethane solution (0.05 m)
of one of the derivatives 3a–f (1 equiv.), containing Et3N
(3.3 equiv.). The mixture was allowed to warm to 0 °C over 1 h,
and thioglucose (1 equiv.) and Et3N (2 equiv.) were then added.
After 15 h of stirring at room temperature, the reaction was
quenched by addition of ice/water and the mixture extracted with
dichloromethane (3ϫ). The collected organic phase was washed
with brine and then dried with MgSO4. After evaporation of the
solvent, the residue was purified by flash chromatography (eluent:
NMR (CDCl3): δ = 8.34 (s, 1 H, NOH), 3.86 (m, J4,5 = 6.0, J4,3
=
6.4 Hz, 1 H, 4-H), 2.88 (q, Jvic = 7.6 Hz, 2 H, SCH2CH3), 2.59
(ddd, J2a,3a = 5.6, J2a,3b = 10.4, J2a,2b = 15.6 Hz, 1 H, 2a-H), 2.42
(ddd, J2b,3a = 5.6, J2b,3b = 10.0 Hz, 1 H, 2b-H), 1.75–1.68 (m, 2 H,
3-H), 1.31 (t, 3 H, SCH2CH3), 1.15 (t, 3 H, CHCH3), 0.89 (s, 9 H,
tBuSiO), 0.05 (s, 6 H, Me2SiO) ppm. 13C NMR (CDCl3): δ = 156.4
(C=N), 67.7 (C-4), 37.1 (C-3), 28.9 (C-2), 25.8 (Me3CSi), 23.7 (C-
5), 23.6 (SCH2CH3), 18.0 (Cq, tBuSi), 15.0 (SCH2CH3), –4.4, –4.8
(Me2SiO) ppm. MS (IS+): m/z = 292 [M + H]+. HRMS (ESI):
calcd. for C13H30NO2SSi 292.1767; found 292.1780.
S-Ethyl
(Z)-4-(tert-Butyldimethylsilyloxy)butanethiohydroximate petroleum ether/EtOAc, 9:1).
(4b): Uncoloured solid (0.51 g, 1.35 mmol, 78%), m.p. 61–63 °C
(petroleum ether/EtOAc), Rf = 0.15 (petroleum ether/EtOAc, 9:1).
1H NMR (CDCl3): δ = 8.58 (s, 1 H, NOH), 3.66 (t, J4,3 = 6.0 Hz,
2 H, 4-H), 2.90 (q, Jvic = 7.2 Hz, 2 H, SCH2CH3), 2.53 (m, 2 H,
2-H), 1.86–1.79 (m, 2 H, 3-H), 1.31 (t, 3 H, SCH2CH3), 0.89 (s, 9
H, tBuSiO), 0.05 (s, 6 H, Me2SiO) ppm. 13C NMR (CDCl3): δ =
156.2 (C=N), 61.9 (C-4), 30.5 (C-2), 29.1 (C-3), 25.9 (Me3CSi),
23.6 (SCH2CH3), 18.2 (Cq, tBuSi), 15.0 (SCH2CH3), –5.4 (Me2SiO)
ppm. MS (IS+): m/z = 278 [M + H]+. HRMS (ESI): calcd. for
C12H27NO2SSiNa 300.1429; found 300.1415.
S-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl) (Z)-4-(tert-Butyldi-
methylsilyloxy)pentanethiohydroximate (6a): Amorphous white so-
lid (0.4 g, 0.67 mmol, 80%), Rf = 0.31 (petroleum ether/EtOAc,
1
3:2), diastereoisomeric mixture. H NMR (CDCl3): δ = 8.86 (s, 0.4
H, NOH), 8.76 (s, 0.6 H, NOH), 5.27–5.20 (m, 1 H, 3-H), 5.13–
5.01 (m, 3 H, 1-H, 2-H, 4-H), 4.24 (dd, Jvic = 5.0, Jgem = 12.4 Hz,
0.4 H, 6a-H), 4.19 (dd, Jvic = 5.0, Jgem = 12.4 Hz, 0.6 H, 6a-H),
4.13 (dd, Jvic = 2.0 Hz, 0.4 H, 6b-H), 4.07 (dd, Jvic = 2.0 Hz, 0.6
H, 6b-H), 3.86 (m, J4,5 = J4,3 = 6.0 Hz, 1 H, 4aglycon-H), 3.76 (ddd,
J5,4 = 10.0 Hz, 0.6 H, 5-H), 3.71 (ddd, J5,4 = 10.0 Hz, 0.4 H, 5-H),
S-Ethyl (Z)-5-(tert-Butyldimethylsilyloxy)pentanethiohydroximate 2.71–2.44 (m, 2 H, 2aglycon-H), 2.05–1.98 (m, 12 H, COCH3), 1.77–
(4c): Yellowish oil (0.09 g, 0.31 mmol, 82%), m.p. 61–63 °C (petro- 1.66 (m, 2 H, 3aglycon-H), 1.15 (d, 1.2 H, CHCH3), 1.14 (d, 1.8 H,
2298
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2293–2300

Glucosinolate Synthesis: a Hydroxamic Acid Approach
CHCH3), 0.90, 0.88 0.87, 0.85 (4 s, 9 H, tBuSiO), 0.06, 0.05, 0.04 25.8 (Me3CSiOAr), 20.7, 20.6, 20.5 (COCH3), 18.3, 18.1 (Cq,
(3 s, 6 H, Me2SiO) ppm. 13C NMR (CDCl3): δ = 170.6, 170.5,
170.2, 170.1, 169.3, 169.1 (COCH3), 152.3, 152.1 (C=N), 79.9 (C-
tBuSi), –4.1, –4.3 (Me2SiOAr), –5.2, –5.3 (Me2SiON) ppm. MS
( I S + ) : m / z = 7 4 3 [ M + H ] + . H R M S ( E S I ) : c a l c d . fo r
1), 75.8, 75.7 (C-5), 73.9, 73.8 (C-3), 70.0, 69.9 (C-2), 67.9 (C-4), C34H56NO11SSi2 742.3113; found 742.3103.
67.8, 67.6 (C-4aglycon), 62.0, 61.9 (C-6), 36.7, 36.6 (C-3aglycon), 29.0,
S-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl) (Z)-2-Phenylethane-
28.6 (C-2aglycon), 25.9, 25.8 (Me3CSi), 23.8, 23.7 (CHCH3), 20.6,
20.5, 20.4 (COCH3), 18.1, 18.0 (Cq, tBuSi), –4.6, –4.5, –4.4 (Me2-
SiO) ppm. MS (IS+): m/z = 594 [M + H]+. HRMS (ESI): calcd. for
C25H43NO11SiSNa 616.2224; found 616.2219.
thiohydroximate (6f):[14] White solid (0.318 g, 0.64 mmol, 85%),
m.p. 150–152 °C (petroleum ether/EtOAc). Rf = 0.43 (petroleum
ether/EtOAc, 3:2). [α]D = –3.2 (c = 0.93, CHCl3). 1H NMR
(CDCl3): δ = 8.16 (s, 1 H, NOH), 7.38–7.28 (m, 5 H, Ar-H), 5.05–
5.01 (m, 2 H, 3-H, 4-H), 4.99–4.94 (m, 1 H, 2-H), 4.79 (d, J1,2
=
S-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl) (Z)-5-(tert-Butyldi-
10.0 Hz, 1-H), 4.14 (dd, J6a,5 = 5.6, J6a,6b = 12.4 Hz, 1 H, H6a),
4.00 (dd, J6b,5 = 2.4 Hz, 1 H, 6b-H), 3.96 (s, 1 H, CH2), 3.49 (ddd,
J5,4 = 9.6 Hz, 1 H, 5-H), 2.08, 2.01, 1.97, 1.96 (4 s, 12 H, COCH3)
ppm. 13C NMR (CDCl3): δ = 170.5, 170.1, 169.3, 169.1 (COCH3),
151.4 (C=N), 135.7 (aryl C-1), 129.0, 128.0, 127.4 (aryl CH), 79.4
(C-1), 75.6 (C-5), 73.7 (C-3), 70.0 (C-2), 67.9 (C-4), 62.1 (C-6), 38.9
(CH2), 20.7, 20.5 (COCH3) ppm. MS (IS+): m/z = 498 [M + H]+.
methylsilyloxy)pentanethiohydroximate (6c): Colourless gum
(0.74 g, 1.245 mmol, 75%), [α]D = –4.6 (c = 0.94, CHCl3), Rf = 0.29
(petroleum ether/EtOAc, 9:1). 1H NMR (CDCl3): δ = 8.78 (s, 1 H,
NOH), 5.28–5.22 (m, 1 H, 3-H), 5.09–5.03 (m, 3 H, 1-H, 2-H, 4-
H), 4.18 (dd, Jvic = 5.6, Jgem = 12.4 Hz, 1 H, 6a-H), 4.10 (dd, Jvic
= 2.0 Hz, 1 H, 6b-H), 3.76 (ddd, J5,4 = 10.0 Hz, 1 H, 5-H), 3.62 (t,
Jvic = 6.0 Hz, 2 H, 5aglycon-H), 2.55–2.50 (m, 2 H, 2aglycon-H), 2.05,
2.02, 2.01, 1.99 (4ϫs, 12 H, COCH3), 1.75–1.64 (m, 2 H, 3aglycon
-
Typical Procedure for NO-Sulfation of Thiohydroximates: A solu-
tion of the thiohydroximate (1 equiv.) in dry dichloromethane was
added under argon to a suspension of 98% SO3/pyridine complex
(0.1 m, 5 equiv.) in dichloromethane. After stirring of the mixture
at room temperature for 24 h, the reaction was quenched by ad-
dition of an aqueous solution of KHCO3 (1 m, 20 equiv.) and the
mixture stirred for a further 30 min. After removal of the solvents,
the crude material was purified by flash chromatography (eluent:
EtOAc/MeOH, 9:1).
H), 1.60–1.51 (m, 2 H, 4aglycon-H), 0.88 (s, 9 H, tBuSiO), 0.04 (s, 6
H, Me2SiO) ppm. 13C NMR (CDCl3): δ = 170.5, 170.2, 169.3,
169.1 (COCH3), 152.0 (C=N), 79.8 (C-1), 75.9 (C-5), 73.8 (C-3),
70.1 (C-2), 68.1 (C-4), 62.5 (C-5aglycon), 62.2 (C-6), 32.3, 32.2 (C-
2aglycon, C-4aglycon), 25.9 (Me3CSi), 23.5 (C-3aglycon), 20.6, 20.5
(COCH3), 18.3 (Cq, tBuSi), –5.3 (Me2SiO) ppm. MS (IS+): m/z =
594 [M + H]+. HRMS (ESI): calcd. for C25H44NO11SiS 594.2404;
found 594.2394.
S-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl) (Z)-2-(tert-Butyldi-
S-(2,3,4,6-Tetra-O-acetyl-β-D-glucopyranosyl) (Z)-5-(tert-butyldi-
methylsilyloxy)-2-phenylethanethiohydroximate (6e): Yellowish
amorphous solid (0.975 g, 1.645 mmol, 62%), [α]D = –1.4 (c = 1.0,
CHCl3), Rf = 0.43 (petroleum ether/EtOAc, 9:1). 1H NMR
(CDCl3): δ = 8.56 (s, 1 H, NOH), 7.20 (dd, J6,4 = 1.2, J6,5 = 8.0 Hz,
1 H, 6aryl-H), 7.16 (dt, J4,3 = J4,5 = 8.0 Hz, 1 H, 4aryl-H), 6.93 (dt,
J5,3 = 0.8 Hz, 1 H, 5aryl-H), 6.84 (dd, 1 H, 3aryl-H), 5.10–5.02 (m,
2 H, 3-H, 4-H), 5.00–4.95 (m, 1 H, 2-H), 4.85 (d, J1,2 = 10.0 Hz,
1-H), 4.13 (dd, Jvic = 4.0, Jgem = 12.4 Hz, 1 H, 6a-H), 3.94 and
3.88 (2 d, Jgem = 16.8 Hz, 2 H, CH2), 3.79 (dd, Jvic = 2.0 Hz, 1 H,
6b-H), 3.40 (ddd, J5,4 = 10.0 Hz, 1 H, 5-H), 2.02, 1.98, 1.96 (3 s,
12 H, COCH3), 1.03 (s, 9 H, tBuSiO), 0.26, 0.24 (2 s, 6 H, Me2SiO)
ppm. 13C NMR (CDCl3): δ = 170.6, 170.1, 169.2, 169.1 (COCH3),
152.6 (C-2aryl), 151.6 (C=N), 129.7 (C-6aryl), 128.3 (C-4aryl), 123.1
(C-1aryl), 121.6 (C-5aryl), 118.8 (C-3aryl), 79.8 (C-1), 75.4 (C-5), 73.9
(C-3), 69.7 (C-2), 67.5 (C-4), 61.4 (C-6), 32.8 (CH2), 25.8 (Me3CSi),
20.6, 20.5, 20.4 (COCH3), 18.2 (Cq, tBuSi), –4.1, –4.3 (Me2SiO)
ppm. MS (IS+): m/z = 629 [M + H]+. HRMS (ESI): calcd. for
C28H41NO11SSi 627.2170; found 627.2164.
methylsilyloxy)pentanethiohydroximate NO-Sulfate, Potassium Salt
(8c): White solid (0.318 g, 0.64 mmol, 66%), m.p. 150–152 °C (pe-
troleum ether/EtOAc), [α]D = –3.0 (c = 0.97, CHCl3), Rf = 0.14
(EtOAc/MeOH, 19:1). 1H NMR (CD3OD): δ = 5.41–5.28 (m, 2 H,
1-H, 3-H), 5.08–4.96 (m, 2 H, 2-H, 4-H), 4.24 (dd, Jvic = 5.6, Jgem
= 12.4 Hz, 1 H, 6a-H), 4.14 (dd, Jvic = 2.0 Hz, 1 H, 6b-H), 4.00
(ddd, J5,4 = 10.0 Hz, 1 H, 5-H), 3.70 (t, Jvic = 6.4 Hz, 1 H, 5aglycon
-
H), 2.68 (t, Jvic = 7.6 Hz, 1 H, 2aglycon-H), 2.06, 2.03, 2.02, 1.98 (4
s, 12 H, COCH3), 1.86–1.70 (m, 2 H, 3aglycon-H), 1.68–1.58 (m, 2
H, 4aglycon-H), 0.92 (s, 9 H, tBuSiO), 0.08 (s, 6 H, Me2SiO) ppm.
13C NMR (CD3OD): δ = 172.2, 171.5, 171.2, 170.9 (COCH3), 159.2
(C=N), 81.0 (C-1), 76.9 (C-5), 75.1 (C-3), 71.5 (C-2), 69.6 (C-4),
63.8 (C-6), 63.4 (C-5aglycon), 33.4, 33.3 (C-2aglycon, C-4aglycon), 26.5
(Me3CSi), 25.0 (C-3aglycon), 20.8, 20.6, 20.5 (COCH3), 19.2 (Cq,
tBuSi), –5.1 (Me2SiO) ppm. MS (IS–): m/z = 672 [M – K]+. HRMS
(ESI): calcd. for C25H42NO14S2Si 672.1816; found 672.1823.
S-(2,3,4,6-Tetra-O-acetyl-β-
methylsilyloxy)-2-phenylethanethiohydroximate NO-Sulfate, Potas-
-glucopyranosyl) (Z)-NO-(tert-Butyl- sium Salt (8e): Amorphous solid (0.103 g, 0.21 mmol, 69%), [α]D =
D-glucopyranosyl) (Z)-2-(tert-Butyldi-
S-(2,3,4,6-Tetra-O-acetyl-β-
D
1
dimethylsilyl)-2-[2-(tert-butyldimethylsilyloxy)phenyl]ethanethio-
hydroximate (7): Yellow oil (0.158 g, 0.21 mmol, 8.4%), [α]D = –2.2
(c = 1.04, CHCl3), Rf = 0.47 (petroleum ether/EtOAc, 9:1). 1H
–2.0 (c = 1.0, MeOH). Rf = 0.20 (EtOAc/MeOH, 19:1). H NMR
(CD3OD): δ = 7.34 (dd, J6,4 = 1.6, J6,5 = 7.6 Hz, 1 H, 6aryl-H), 7.22
(dt, J4,3 = J4,5 = 7.6 Hz, 1 H, 4aryl-H), 6.99 (dt, J5,3 = 1.2 Hz, 1 H,
5aryl-H), 6.69 (dd, 1 H, 3aryl-H), 5.07 (ft, Jvic = 9.2 Hz, 1 H, 3-H),
5.00–4.95 (m, 2 H, 2-H, 4-H), 4.87 (d, J1,2 = 9.2 Hz, 1-H), 4.10
NMR (CDCl3): δ = 7.20 (dd, J6,4 = 1.6, J6,5 = 7.6 Hz, 1 H, 6aryl
H), 7.15 (dt, J4,3 = J4,5 = 7.6 Hz, 1 H, 4aryl-H), 6.93 (dt, J5,3
-
=
0.8 Hz, 1 H, 5aryl-H), 6.84 (dd, 1 H, 3aryl-H), 5.05–4.99 (m, 2 H, 3- (dd, Jvic = 4.0, Jgem = 12.4 Hz, 1 H, 6a-H), 4.06 and 3.97 (2 d, Jgem
H, 4-H), 4.93 (br. t, J2,3 = 10.0 Hz, 1 H 2-H), 4.75 (d, J1,2
10.0 Hz, 1-H), 4.13 (dd, Jvic = 3.6, Jgem = 12.4 Hz, 1 H, 6a-H), 3.94
and 3.88 (2 d, Jgem = 16.8 Hz, 2 H, CH2), 3.67 (dd, Jvic = 2.4 Hz,
=
= 16.8 Hz, 2 H, CH2), 3.74 (dd, Jvic = 2.4 Hz, 1 H, 6b-H), 3.47
(ddd, J5,4 = 10.0 Hz, 1 H, 5-H), 2.01, 1.97, 1.94, 1.93 (4 s, 12 H,
COCH3), 1.09 (s, 9 H, tBuSiO), 0.34, 0.29 (2 s, 6 H, Me2SiO) ppm.
1 H, 6b-H), 3.32 (m, 1 H, 5-H), 2.02, 1.97, 1.96, 1.95 (4 s, 12 H, 13C NMR (CD3OD): δ = 172.2, 171.4, 171.0, 170.7 (COCH3), 158.2
COCH3), 1.05 (s, 9 H, tBuSiOAr), 0.93 (s, 9 H, tBuSiON), 0.29, (C=N), 153.9 (C-2aryl), 130.9 (C-6aryl), 129.6 (C-4aryl), 127.3 (C-
0.25 (2 s, 6 H, Me2SiOAr), 0.17 (br. s, 6 H, Me2SiON) ppm. 13C
1aryl), 123.2 (C-5aryl), 120.5 (C-3aryl), 81.4 (C-1), 76.7 (C-5), 75.2
NMR (CDCl3): δ = 170.6, 170.1, 169.2, 169.0 (COCH3), 155.7 (C- (C-3), 71.0 (C-2), 69.0 (C-4), 62.7 (C-6), 33.8 (CH2), 26.5 (Me3CSi),
2aryl), 152.4 (C=N), 129.4 (C-6aryl), 128.0 (C-4aryl), 126.7 (C-1aryl), 20.6, 20.5, 20.4 (COCH3), 19.3 (Cq, tBuSi), –3.8, –4.1 (Me2SiO)
121.7 (C-5aryl), 118.8 (C-3aryl), 79.9 (C-1), 75.3 (C-5), 74.1 (C-3), ppm. MS (IS–): m/z = 707 [M – K]+. HRMS (ESI): calcd. for
69.8 (C-2), 67.5 (C-4), 61.2 (C-6), 32.3 (CH2), 26.0 (Me3CSiON), C28H40NO14S2Si 706.1660; found 706.1671.
Eur. J. Org. Chem. 2011, 2293–2300
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2299

D. Cerniauskaite, J. Rousseau, A. Sackus, P. Rollin, A. Tatibouët
FULL PAPER
Panstruga, A. Sanchez-Vallet, A. Molina, P. Schulze-Lefert,
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Typical Procedure for Deprotection of the D-Gluco Moiety: A freshly
prepared solution of potassium methoxide (1 m) was added under
argon to a suspension of a peracetylated NO-sulfated derivative 8
(1 equiv.) in dry MeOH (0.25 m, 5 mL) until the pH reached 8. The
solution was left at room temperature for 3 h, and the reaction was
then quenched with Amberlite® IR+. After filtration and concen-
tration in vacuo, the resulting crude product was purified by col-
umn chromatography.
[5]
[6]
[7]
S-(β-D-Glucopyranosyl) (Z)-5-Hydroxypentanethiohydroximate NO-
Sulfate, Potassium Salt (9): Amorphous solid (0.01 g, 0.024 mmol,
79%), [α]D = –2.9 (c = 1, H2O), Rf = 0.31 (EtOAc/MeOH, 19:1).
1H NMR (CD3OD): δ = 4.41 (d, J1,2 = 9.2 Hz, 1 H, 1-H), 3.90–
3.83 (m, 2 H, 6a-H, 6b-H), 3.67–3.59 (m, 2 H, 3-H, 5-H), 3.55 (t,
Jvic = 6.4 Hz, 2 H, 5aglycon-H), 3.41–3.36 (m, 2 H, 2-H, 4-H), 2.35
(t, Jvic = 7.2 Hz, 1 H, 2aglycon-H), 1.71–1.64 (m, 2 H, 3aglycon-H),
1.58–1.51 (m, 2 H, 4aglycon-H) ppm. 13C NMR (CD3OD): δ = 152.7
(C=N), 82.5 (C-1), 79.7 (C-5), 79.3 (C-3), 73.2 (C-2), 71.4 (C-4),
62.8 (C-6), 62.4 (C-5aglycon), 34.6 (C-2aglycon), 33.0 (C-4aglycon), 22.0
(C-3aglycon) ppm. MS (IS–): m/z = 390 [M – K]+. HRMS (ESI):
calcd. for C11H20NO10S2 390.0529; found 390.0532.
[8]
[9]
[10]
[11]
(Z)-S-(β-D-Glucopyranosyl) 2-(2-Hydroxyphenyl)ethanethiohydrox-
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0.185 mmol, 88%), [α]D = –3.1 (c = 1, H2O), Rf = 0.31 (EtOAc/
1
MeOH, 19:1). H NMR (CD3OD): δ = 7.22 (dt, 1 H, J4,3 = J4,5
=
7.6 Hz, 4aryl-H), 7.18 (dd, 1 H, J6,4 = 1.6, J6,5 = 7.6 Hz, 6aryl-H),
6.80–6.75 (m, 2 H, 3aryl-H, 5aryl-H), 4.66 (d, 1 H, J1,2 = 9.6 Hz, 1-
H), 4.19 (d, 1 H, Jgem = 16.4 Hz, CHa), 3.77 (dd, 1 H, Jvic = 2.4,
Jgem = 12.4 Hz, 6a-H), 3.71–3.64 (m, 2 H, 6b-H, CHb), 3.43–3.35
(m, 3-H), 3.25 (ddd, 1 H, J5,4 = 9.6 Hz, 5-H), 3.23–3.17 (m, 2 H,
2-H, 4-H). 13C NMR (CD3OD): δ = 155.6, 154.4 (C-2aryl, C=N),
130.1 (C-6aryl), 128.9 (C-4aryl), 124.5 (C-1aryl), 120.8 (C-5aryl), 116.1
(C-3aryl), 83.0 (C-1), 81.5 (C-5), 79.6 (C-3), 74.4 (C-2), 70.8 (C-4),
62.3 (C-6), 32.5 (CH2). MS (IS+): m/z = 424 [M – K]+. HRMS
(ESI): calcd. for C14H18NO10S2 424.0372; found 424.0385.
Acknowledgments
The authors would like to thank the French Embassy in Lithuania
for a scholarship (D. C.).
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Received: October 21, 2010
Published Online: March 15, 2011
2300
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 2293–2300