Short synthesis, X-ray and conformational analysis of a cyclic peracetylated l-sorbose-derived nitrone, a useful intermediate towards N-O-containing d-gluco-iminosugars

Article abstract of DOI:10.1039/c8nj03868f

The synthesis of the peracetylated ketonitrone 4 is described in four steps from l-sorbose. This cyclic nitrone is crystalline and proved to preferentially adopt a ⁴H₃ conformation with all acetate groups in pseudo-axial orientation. Nitrone 4 undergoes regioselective cycloadditions with alkynes, affording tetra-O-acetyl-isoxazolines with good yields and stereoselectivities (4 : 1 to 9 : 1 diastereomeric ratio). Nitrone 4 and the obtained isoxazolines were smoothly deacetylated to produce the polyhydroxylated nitrone 5 and novel iminosugars containing an isoxazoline motif. Evaluation of their glycosidase inhibitory activity demonstrated their rather weak, but selective affinity for a variety of enzymes.

Full text of DOI:10.1039/c8nj03868f

NJC
View Article Online
View Journal
PAPER
Short synthesis, X-ray and conformational analysis
of a cyclic peracetylated L-sorbose-derived
nitrone, a useful intermediate towards
Cite this:DOI: 10.1039/c8nj03868f
N–O-containing D-gluco-iminosugars†
Salia Tangara,a Alice Kanazawa, *a Martine Fayolle,a Christian Philouze,a
a
b
a
Jean-François Poisson,
Jean-Bernard Behr
and Sandrine Py
*
The synthesis of the peracetylated ketonitrone 4 is described in four steps from L-sorbose. This cyclic
nitrone is crystalline and proved to preferentially adopt a 4H3 conformation with all acetate groups in
pseudo-axial orientation. Nitrone 4 undergoes regioselective cycloadditions with alkynes, affording
tetra-O-acetyl-isoxazolines with good yields and stereoselectivities (4 : 1 to 9 : 1 diastereomeric ratio).
Nitrone 4 and the obtained isoxazolines were smoothly deacetylated to produce the polyhydroxylated
nitrone 5 and novel iminosugars containing an isoxazoline motif. Evaluation of their glycosidase
inhibitory activity demonstrated their rather weak, but selective affinity for a variety of enzymes.
Received 1st August 2018,
Accepted 6th September 2018
DOI: 10.1039/c8nj03868f
rsc.li/njc
Introduction
Carbohydrate-derived nitrones1 are key intermediates for the
synthesis of polyhydroxylated alkaloids and iminosugars, which
are sugar analogues with a nitrogen atom in place of the endo-
cyclic oxygen atom. Iminosugars are a major class of synthetic
targets due to their therapeutic potential, generally associated with
their ability to inhibit glyco-processing enzymes.2
Among the cyclic nitrones described to date, the vast majority
is O-benzyl-protected due to the compatibility of benzyl ethers
with the steps involved in their preparation from carbohydrates.
Moreover, easy conversion of benzyl ethers into hydroxyls by
hydrogenolysis is usually performed in the last stages of imino-
sugar syntheses. A few years ago, we applied tetra-O-benzyl-
protected ketonitrones (prepared from inexpensive D-fructose3
or L-sorbose4) to the synthesis of original iminosugars bearing a
quaternary center a to their nitrogen atom. In particular, the
L-sorbose benzylated ketonitrone 1 was successfully used in the
synthesis of the polyhydroxylated indolizidine 24 and quinolizidine
3,5 which were revealed to be potent and selective a-glucosidase
inhibitors with nanomolar Ki values (Scheme 1). Such carbo-
hydrate derived-nitrones could also give access to iminosugars
containing a N–O bond, for which little is known concerning
Scheme 1 Ketonitrones as intermediates for new iminosugar synthesis.
glycosidase inhibition potency.6 Although such compounds
could in principle be obtained through cleavage of benzyl ethers
using BCl3 to avoid N–O bond destructive hydrogenolysis,3,7 we
thought that the use of O-acyl-protected nitrones could be
advantageous to allow a hydroxyl-deprotection step under
mild conditions. We thus intended to prepare nitrone 4, the
O-acetylated analogue of nitrone 1, and to study its reactivity in
cycloaddition reactions with alkynes to form 4-isoxazolines, a
class of compounds for which glycosidase inhibition has yet not
been reported. Noteworthily, examples of O-acylated nitrones
are very scarce in the literature.8
a Univ. Grenoble Alpes, DCM, F-38000 Grenoble, France CNRS, DCM,
F-38000 Grenoble, France. E-mail: Alice.Kanazawa@univ-grenoble-alpes.fr,
Sandrine.Py@univ-grenoble-alpes.fr
Results and discussion
While three steps are necessary for the synthesis of tetra-O-
benzyl-L-sorbose from L-sorbose,4 only one step is required to
prepare tetra-O-acetyl-L-sorbose (7). This protected ketose has
been previously obtained in 65% yield by treating L-sorbose
b Univ. Reims Champagne-Ardenne, ICMR, CNRS UMR 7312, 51687 Reims Cedex 2,
France
† Electronic supplementary information (ESI) available. CCDC 1587933 (4). For ESI and
crystallographic data in CIF or other electronic format see DOI: 10.1039/c8nj03868f
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018
New J. Chem.

View Article Online
Paper
NJC
half-chair conformation with all acetate substituents in pseudo-
axial orientation is more stable than that bearing all-equatorial
acetates, although the free energy difference is small (DG298
1 kcal molꢁ1, see ESI†).17
=
Nitrone 4 was engaged in cycloaddition reactions with
various alkynes to prepare isoxazolines (Table 1). The cyclo-
additions with phenylacetylene, cyclohexylacetylene, trimethyl-
silylacetylene, propargyl acetate, 1-pentyne and 1-hexyne were
slow, but occurred smoothly at room temperature, and led to
isoxazolines 10a–f and 100a–f in good yields (78–97%). These
reactions proved to be completely regioselective, yielding only
the C-5 substituted isoxazolines 10a–f. However, cycloadditions
with nitrone 4 were not as diastereoselective as with nitrone 1,18
and minor diastereoisomers 100a–f could not be separated by
chromatography from 10a–f (10 : 100 = 4 : 1 to 9 : 1).
Scheme 2 Synthesis of nitrone 4 from L-sorbose.
with acetic anhydride in pyridine.9 We found that acylation of
L-sorbose in the presence of acetyl chloride yielded the protected
derivative 7 (84%) with better efficiency (Scheme 2).10 In the next
step, the in situ generation of the PPh3ꢀBr2 brominating reagent
was preferred to the commercially available complex as the
latter exhibited variable efficiency depending on the batches.
Thus, triphenylphosphine and pyridinium tribromide in the
presence of pyridine were used to perform concomitant hemi-
ketal ring opening and C-6 bromination of 7,11 allowing the
isolation of bromoketone 8 in excellent yield (89%). The direct
transformation of 8 into nitrone 4 by using the same protocol
used for the synthesis of 1 was not possible in this case. Treating
bromoketone 8 with hydroxylamine only led to complex mixtures,
in which the presence of 4 could not be detected by NMR
analysis. A significant loss of material after extraction suggested
deacetylation in the presence of hydroxylamine.12 Bromoketone 8
was thus treated with tert-butyldimethylsilyloxyamine13 in the
presence of MgSO4 in refluxing toluene to yield the bromo-oxime
9 in 66% yield. Remarkably, only the E stereoisomer was formed
in this case. Finally, the target nitrone 4 was obtained in 61%
yield by a desilylation/cyclisation sequence induced by treatment
with TBAF on silica at 0 1C.14 The crystalline and stable nitrone 4
was thus synthetized in 4 steps from L-sorbose in 30% overall
yield. Its preparation can be applied to the multigram scale.
The analysis by X-ray diffraction of a monocrystal of nitrone
4 unambiguously confirmed its structure and depicted a half-
chair conformation in which the acetate substituents are in
pseudo-axial orientations (Fig. 1).15 NMR data also support the
preference for pseudo-axial positioning of the acetate groups in
Table 1 Cycloaddition of nitrone 4 with alkynes at room temperature
Reaction time Global yield dr
Entry Alkyne Cycloadduct
(days)
(%)
10 : 100
1
3
90
4 : 1
2a
4
2
2
78
97
92
9 : 1
9 : 1
4 : 1
3
3
solution (broad singlet for H, meaning that J3H,4H o 2 Hz in
CDCl3). This conformation could be favored over the half-chair
exhibiting pseudo-equatorial acetate groups due to through-
space electrostatic stabilization of the (CQN)+ function by axial
acyloxy groups, as previously demonstrated for 6-membered
cyclic oxocarbeniums.16 DFT calculations confirmed that the
4
5a
17
12
Not purified 9 : 1
Not purified 9 : 1
6a
a
A small volume of dichloromethane was added to solubilize the
Fig. 1 Views of the X-ray structure of nitrone 4.
reactants, nitrone 4 being poorly soluble in the alkyne.
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018

View Article Online
NJC
Interestingly, the major isoxazolines 10a–f (of R configuration
Paper
at the quaternary center as deduced from nOe analyses, see ESI†)
exhibit the D-gluco configuration that proved essential for the
biological activities of 2 and 3.4,5 The dominant reaction pathway
thus results from the preferential approach of the alkyne from the
Si face of the nitrone. This is consistent with an axial approach of
3
the alkyne on the minor H4 conformer of nitrone 4, forming a
favored chair-like transition (pathway a) state rather than the
higher-energy twist boat that would result from addition of the
alkyne through the other axial trajectory (pathway b), i.e. anti to
the C-3 acetoxy substituent (Scheme 3). The axial approach
favoring chair-like transition states is known to be favored in
nucleophilic additions to both 6-membered oxonium19 and
iminium20 ions.
The stereochemical outcome of the cycloaddition of alkynes
to nitrone 4 thus suggests a fast equilibrium between its 4H3
and 3H4 conformers, and a faster cycloaddition of the latter,
exhibiting pseudo-equatorial acetate groups, over the slightly
more stable 4H3 conformer. The formation of the minor dia-
stereoisomers 100 could arise either from an axial approach of
the alkyne to develop a chair-like transition state on the 4H3
conformer of the nitrone (not shown), or from the disfavored
twist-boat transition state occurring in pathway b from the 3H4
conformer (Scheme 3). In contrast to the numerous studies on
cycloadditions involving 5-membered ring nitrones and
alkenes,21 cycloadditions to cyclic 6-membered ring nitrones
are less common and their stereoselectivity has rarely been
discussed.22 The model proposed here, involving addition of
the dipolarophile to the nitrone via a favored axial trajectory,
can also explain previous results reported by van den Broek23
and by Peer and Vasella (with dipolarophiles different from
alkynes).24 In light of these results, DFT energy minimization
calculations were also performed on the two half-chair conforma-
tions of nitrone 1 (see ESI†).17,18 The most stable conformer is also
the 3H4 conformer exhibiting pseudo axial benzyloxy groups, and in
this case, the free energy difference (DG298 = 0.5 kcal molꢁ1) between
conformers is smaller.
Scheme 4 Deacetylation of nitrone 4 and isoxazolines 10.
Nitrone 4 and isoxazolines 10,100 were next easily deprotected
under mild conditions by treatment with a saturated solution of
ammonia in methanol, affording the polyhydroxylated nitrone 5
in good yield (81%, Scheme 4).25 The polyhydroxylated isoxazo-
lines 6a–f and 60a–f could also be obtained in good yields under
the same conditions. Gratifyingly, after deacetylation, the major
diastereomer 6a could be isolated pure by recrystallization in
methanol. Here again, the measured coupling constant J 4H–5H
of 8.8 Hz (d 3.92 ppm) for 6a suggests that this compound adopts
4
mostly a C1 conformation in d4-methanol.
Biological activities
According to NMR data, the major isoxazolines 10 formed The polyhydroxylated nitrone 5 and isoxazolines 6 synthesized
from the cycloaddition of nitrone 4 with alkynes all adopt a from nitrone 4 were next evaluated as glycosidase inhibitors
4
4
chair C1 conformation in the piperidine ring. Indeed, the H–5H using a panel of commercial enzymes.26 Nitrone 5 and isoxazoline
coupling constants in these compounds exhibit typical values for 6a were tested as pure compounds (single stereoisomer), whereas
diaxial proton coupling (10.1 Hz o J4H–5H o 10.6 Hz).
isoxazolines 6b and 6d–f were tested as mixtures of diastereomers.
Inhibition of rice a-glucosidase, yeast a-glucosidase, almond
b-glucosidase, b-glucosidase from Aspergillus niger, b-galactosidase
from Aspergillus oryzae, Jack bean a-mannosidase, bovine liver
a-fucosidase and a-rhamnosidase from Aspergillus niger was first
evaluated at 1 mM concentration of inhibitor (Table 2). When
almost complete inhibition (495%) occurred at this concentration,
IC50 (the concentration of inhibitor affording half the initial rate of
the considered glycosidase) was further determined. In the case of
an inhibition rate between 90% and 95%, an additional assay was
performed at a concentration of 100 mM (see footnotes of Table 2).
Nitrone 5 and isoxazolines 6a,b,e,f are all inhibitors of
a-glucosidase from rice at 1 mM concentration. Nitrone 5 and
isoxazoline 6a are the most active, with IC50 values of 16 and
50 mM, respectively. However, these values are three orders
Scheme 3 Stereochemical model for alkyne cycloadditions to nitrone 4.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018
New J. Chem.

View Article Online
Paper
NJC
Table 2 Glycosidase inhibitiona,b
Enzyme
5
6a
6b/60b
6d/60d
6e/60e
6f/60f
a-glucosidase (rice)
95%c
5%
16%
11%
15%
8%
96%d
49%
94%h
93%i
37%
NI
92%e
74%
ꢁ7% j
NI
15%
ꢁ13%j
8%
43%
ꢁ26% j
ꢁ7% j
NI
92%f
11%
ꢁ24%j
NI
91%g
30%
ꢁ8%j
NI
a-glucosidase (Sac. cerevisiae)
b-glucosidase (almond)
b-glucosidase (Asp. niger)
b-galactosidase (Asp. orizae)
a-mannosidase (Jack bean)
a-rhamnosidase (Asp. niger)
NI
NI
NI
ꢁ8%j
NI
ꢁ6%j
10%
ꢁ12%j
7%
33%
46%
a
% inhibition at 1 mM concentration of inhibitor (less than 5% inhibition/activation was regarded as no impact of the inhibitor on enzyme
b
c
d
e
f
g
activity). NI means no impact on enzyme activity. IC50 = 16 mM. IC50 = 50 mM. 39% inhibition at 100 mM. 33% inhibition at 100 mM. 41%
inhibition at 100 mM. 20% inhibition at 100 mM. 18% inhibition at 100 mM. Negative values mean increase of enzyme activity.
h
i
j
of magnitude higher than other D-gluco-configured bicyclic through methanolic aminolysis of acetates gave access to the
iminosugars bearing a hydroxymethyl substituent at the ring polyhydroxylated nitrone 5 and to unprecedented iminosugars
junction (IC50 in the nanomolar range).4,5 Isoxazolines 6b,e,f 6a–f containing an isoxazoline motif. These compounds were
are less efficient inhibitors, with IC50 values above 100 mM, as evaluated as glycosidase inhibitors and most of them were found
reflected by the remaining a-glucosidase activity measured at to be weak but selective inhibitors of rice a-glycosidase.
this concentration. Compound 6d, which features an extra hydro-
xymethyl group, is only a moderate inhibitor of a-glucosidase
from rice (43% at 1 mM) and it has no inhibition capacity
Experimental
towards all other tested enzymes. Such a detrimental impact of
additional hydroxyl groups onto the fused cycle has already been
observed previously with hydroxylated analogues of indolizidine
24 and quinolizidine 3.5 Compounds 5 and 6b,d,e,f only margin-
ally interfere with the other glycosidases. Only 6a, which features
an aromatic moiety on the isoxazoline ring, proved active against
b-glucosidases from almond and from Aspergillus niger (94% and
93% inhibition, respectively). However, a sharp decrease of
inhibition potency occurred in a dose-dependent manner affording
only 20% remaining inhibition at 100 mM for both enzymes. The
weak basicity of the nitrogen atom in isoxazolines 6 (in comparison
to that of iminosugars such as 2 and 3) probably disfavours
protonation under the assay conditions, and could account for their
limited performance as transition state mimics.
Unexpectedly, a significant increase in the activity of a-gluco-
sidase (yeast) was observed in the presence of 6d at 1 mM con-
centration (26% activation). Similarly, isoxazolines 6b,d,e,f behave as
activators of b-glucosidase and of a-mannosidase. This phenomenon
is quite commonly encountered while performing glycosidase assays
in the presence of carbohydrate analogues,27 but it is not
systematically included in the tables reporting inhibition values
(for the sake of simplicity, it is sometimes referred to as NI, no
inhibition). The mechanism of activation of glycosidases by
saccharides or analogues is currently unknown but allosteric
regulation or modification of the assay-solution properties by
the activator has been suggested as a possible explanation.28
General remarks
Reactions were performed under a positive pressure of dry
argon in oven-dried glassware equipped with a magnetic stir
bar. Standard inert atmosphere techniques were used in hand-
ling all air and moisture sensitive reagents. THF and toluene were
freshly distilled from sodium; CH2Cl2 and pyridine were distilled
from CaH2. Purchased reagents were used without purification.
Reactions were monitored by thin layer chromatography (TLC)
using commercial aluminum-backed silica gel plates. TLC spots
were viewed under ultraviolet light and by heating the plate after
treatment with a 3% solution of potassium permanganate in 10%
aqueous potassium hydroxide (w/v). Product purification by
gravity column chromatography was performed using Silica Gel
60 (70–230 mesh). Optical rotations were measured on a Perkin
Elmer 341 polarimeter. Infrared spectra were obtained from neat
compounds on a Nicolet ‘‘Magna 550’’ spectrometer using an
ATR (attenuated total reflexion) module. The data are reported in
reciprocal centimeters (cmꢁ1). 1H NMR and 13C NMR spectra were
recorded on a Bruker Avance 500 (1H: 500 MHz, 13C: 125 MHz)
spectrometer. Chemical shifts for 1H spectra are values from residual
chloroform in CDCl3 (d 7.26 ppm), residual acetone in (CD3)2CO
(d 2.05 ppm) or residual methanol in CD3OD (d 3.31 ppm). Chemical
shifts for 13C spectra are values from CDCl3 (d 77.16 ppm), (CD3)2CO
(d 29.84 ppm) or CD3OD (d 49.00 ppm). 1H NMR spectra are reported
as following: chemical shift (ppm), multiplicity (br: broad; s: singlet;
d: doublet; dd: doublet of doublets; ddd: dedoubled doublet of
doublets; t: triplet; ps t: pseudo triplet; td: triplet of doublets; m:
multiplet), coupling constants (Hz) and integration. Proton and
carbon signal assignments were established using COSY, HSQC,
and HMBC experiments. High-resolution mass spectra (HRMS) were
recorded on a Waters G2-S Q-TOF mass spectrometer.
Conclusions
In conclusion, a short synthetic route to the peracetylated
ketonitrone 4 was developed from L-sorbose. The latter was
used in cycloaddition reactions with alkynes, which afforded
the corresponding bicyclic isoxazolines in high yields, with
excellent regioselectivity and significant stereoselectivity in favour
Experimental protocols
(2R,3S,4R,5S)-2-(Acetoxymethyl)-2-hydroxytetrahydro-2H-pyran-
of the D-gluco-configured compounds. An easy deprotection 3,4,5-triyl triacetate (7). L-Sorbose (10.0 g, 55.5 mmol) was
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018

View Article Online
NJC
Paper
dissolved in dry pyridine (150 mL) at room temperature. pyridinium p-toluenesulfonate (374 mg, 1.49 mmol) were added
The solution was cooled to ꢁ10 1C and kept for 1 h at this successively. The mixture was heated at reflux for 1 h whereupon
temperature. Acetyl chloride (16.2 mL, 228 mmol) was then solid NaHCO3 was added to neutralise PPTS. After filtration over
added dropwise (in around 45 min), the temperature of the Celite, the solids were rinsed with dichloromethane and the filtrate
mixture being kept at ꢁ5 1C. The final solution was stirred at was concentrated under vaccum to give a residue, which, upon
ꢁ10 1C for 3 h and at room temperature for 40 min. After chromatography (pentane/ether 9 : 1 to 7 : 3), yielded oxime 9
dilution in dichloromethane, the mixture was poured into a 2 M (3.24 g, 66%) as a brown oil. [a]2D0 = ꢁ9.2 (c = 1.08, CHCl3). IR
HCl aqueous solution. The organic phase was then separated n = 3072, 2958, 2935, 2859, 1746, 1428, 1371, 1207, 1115, 1044, 966,
and washed twice with HCl solution followed by washing with a 948 cmꢁ1. 1H NMR (500 MHz, CDCl3) d = 7.68–7.58 (m, 4H, ArCH),
3
4
saturated aqueous NaHCO3 solution. After drying over anhydrous 7.47–7.32 (m, 6H, ArCH), 5.74–5.63 (m, 2H, CH and CH), 5.22
1
MgSO4, the organic phase was filtered and concentrated under (d of AB system, J = 15.9 Hz, 1H, CH2), 5.16 (td, J = 5.5, 6.7 Hz,
5
1
vacuum to give a residue, which was purified by chromatography 1H, CH), 5.11 (d of AB system, J = 15.9 Hz, 1H, CH2), 3.28 (d,
(pentane/ether 9 : 1) affording tetra-O-acetylated-L-sorbose 7 J = 5.6 Hz, 2H, 6CH2), 2.16 (s, 3H, AcCH3), 2.04 (s, 3H, AcCH3),
(16.16 g, 84%) as a white solid. M.p. 91–93 1C. [a]2D0 = ꢁ21.6 1.92 (s, 3H, AcCH3), 1.89 (s, 3H, AcCH3), 1.10 (s, 9H, t-BuCH3) ppm.
(c = 1.02, CHCl3). IR n = 3551, 2977, 1750, 1736, 1700, 1369, 13C NMR (125 MHz, CDCl3) d = 169.9 (AcCO), 169.9 (AcCO), 169.8
1218, 1168, 1036 cmꢁ1. 1H NMR (500 MHz, CDCl3) d = 5.52 (ps t, (AcCO), 169.8 (AcCO), 156.2 (2Cq), 135.6 (ArCH), 135.6 (ArCH), 132.8
4
3
J = 9.8 Hz, 1H, CH), 5.07 (d, J = 9.9 Hz, 1H, CH), 5.02 (ddd, (ArCq), 132.8 (ArCq), 130.1 (ArCH), 130.0 (ArCH), 127.9 (ArCH), 127.8
J = 6.2, 9.8, 10.6 Hz, 1H, 5CH), 4.18 (d of AB system, J = 11.8 Hz, (ArCH), 70.7 (5CH), 70.5 (4CH), 69.1 (3CH), 58.5 (1CH2), 27.1 (6CH2),
1H, 1CH2), 3.97 (d of AB system, J = 11.8 Hz, 1H, 1CH2), 20.9 (AcCH3), 20.7 (AcCH3), 20.6 (AcCH3), 20.5 (AcCH3) ppm. HRMS
6
3.90–3.80 (m, 2H, CH2), 3.41 (s, 1H, OH), 2.12 (s, 3H, AcCH3), (ESI+): calcd for C30H38BrNaNO9Si [M + Na]+ 686.1397; found
2.09 (s, 3H, AcCH3), 2.03 (s, 3H, AcCH3), 2.02 (s, 3H, AcCH3) ppm. 686.1385.
13C NMR (125 MHz, CDCl3) d = 171.1 (AcCO), 170.3 (AcCO), 170.1
(3S,4R,5R)-3,4,5-Triacetoxy-6-(acetoxymethyl)-2,3,4,5-tetrahydro-
(
AcCO), 169.8 (AcCO), 95.8 (2Cq), 70.7 (4CH), 70.4 (3CH), 69.2 pyridine 1-oxide (4). To a solution of bromide 9 (4.02 g, 6.05 mmol)
(5CH), 65.9 (1CH2), 59.5 (6CH2), 20.8 (AcCH3), 20.8 (AcCH3), in THF (135 mL), TBAF supported on silica gel (6.7 g, 8.28 mmol)
20.7 (AcCH3), 20.7 (AcCH3). HRMS (ESI+): calcd for C14H20NaO10 was added at 0 1C, and the mixture was stirred for 1 h. After
[M + Na]+ 371.0954; found 371.0957.
filtration, the solid was rinsed with THF. The filtrate was
(3S,4S,5R)-6-Bromo-2-oxohexane-1,3,4,5-tetrayl tetraacetate concentrated under vacuum and the residue was purified by
(8). To a solution of triphenylphosphine (9.09 g, 34.6 mmol) chromatography (AcOEt/MeOH 95 : 5) to afford nitrone 4 (1.27 g,
in THF (90 mL) was added pyridinium tribromide (11.04 g, 61%) as a white solid. M.p. 106–107 1C. [a]2D0 = ꢁ63.5 (c = 1.07,
34.5 mmol) and the mixture was stirred for 20 minutes at room CHCl3). IR n = 2981, 2950, 1737, 1434, 1370, 1208, 1047,
1
3
temperature. Compound 7 (6 g, 17.2 mmol) in THF (45 mL) and 1022 cmꢁ1. H NMR (500 MHz, CDCl3) d = 5.72 (br s, 1H, CH),
pyridine (5.5 mL, 69.0 mmol) were then added and the resultant 5.23 (d, J = 16.6 Hz, 1H, 1CH2), 5.22–5.16 (m, 2H, 4CH and 5CH),
mixture was heated at reflux for 1 h. After dilution in ethyl acetate, 4.95 (d, J = 16.6 Hz, 1H, 1CH2), 4.23 (dd, J = 1.6, 16.1 Hz, 1H, 6CH2),
the organic phase was washed successively with a saturated Na2S2O3 4.01 (br d, J = 16.1 Hz, 1H, 6CH2), 2.11 (s, 3H, AcCH3), 2.08 (s, 3H,
aqueous solution, aqueous 2 M HCl solution and with brine. After AcCH3), 2.06 (s, 3H, AcCH3), 2.04 (s, 3H, AcCH3) ppm. 13C NMR
drying over MgSO4, the organic phase was filtered and concentrated (125 MHz, CDCl3) d = 170.2 (AcCO), 169.4 (AcCO), 169.0 (AcCO),
under vacuum. The crude solid was washed with ether and 168.7 (AcCO), 138.5 (2Cq), 65.8 (4CH), 65.4 (5CH), 65.3 (3CH),
discarded. The ethereal solution was evaporated to give an oily 60.0 (1CH2), 59.4 (6CH2), 20.7 (AcCH3), 20.7 (AcCH3), 20.6
residue that was purified by chromatography (pentane/ether 3 : 7) to
afford bromoketone 8 (6.26 g, 89%) as a yellow oil. [a]2D0 = +21.1 (c = [M + H]+ 346.1138; found 346.1133.
(
AcCH3), 20.6 (AcCH3) ppm. HRMS (ESI+): calcd for C14H20NO9
0.99, CHCl3). IR n = 2941, 1750, 1431, 1371, 1200, 1042 cmꢁ1
.
(3aR,4R,5R,6S)-3a-(Acetoxymethyl)-2-phenyl-3a,4,6,7-tetrahydro-
1H NMR (500 MHz, CDCl3) d = 5.71 (dd, J = 3.7 Hz, J = 5.6 Hz, 1H, 5H-isoxazolo[2,3-a]pyridine-4,5,6-triyl triacetate (10a). A mixture of
4CH), 5.43 (d, J = 3.7 Hz, 1H, 3CH), 5.27 (ddd, J = 5.3, 5.3, 11.0 Hz, nitrone 4 (264 mg, 0.76 mmol) and phenylacetylene (1.3 mL,
1H, 5CH), 4.83 (d of AB system, J = 17.1 Hz, 1H, 1CH2), 4.77 (d of AB 11.5 mmol) was stirred at room temperature for 3 days. After
1
system, J = 17.1 Hz, 1H, CH2), 3.52 (dd of ABX system, J = 5.3, concentration under reduced pressure, the residue was purified
6
11.0 Hz, 1H, CH2), 3.41 (dd of ABX system, J = 5.3, 11.0 Hz, 1H, by chromatography over silica gel (pentane/EtOAc 7 : 3) to give
6CH2), 2.20 (s, 3H, AcCH3), 2.16 (s, 3H, AcCH3), 2.12 (s, 3H, AcCH3), cycloadducts 10a and 100a (310 mg, 90%) as a white foam
2.09 (s, 3H, AcCH3) ppm. 13C NMR (125 MHz, CDCl3) d = 197.1 (mixture of two unseparated diastereoisomers, dr = 4 : 1). M.p.
(AcCO), 169.9 (AcCO), 169.8 (AcCO), 169.72 (AcCO), 169.66 (AcCO), 73.8 43–45 1C. IR n = 2969, 1750, 1649, 1494, 1448, 1367, 1212, 1031
(3CH), 70.3 (5CH), 70.0 (4CH), 66.7 (1CH2), 29.3 (6CH2), 20.7 (AcCH3), cmꢁ1. Major diastereoisomer: 1H NMR (400 MHz, CDCl3)
20.6 (AcCH3), 20.56 (AcCH3), 20.54 (AcCH3) ppm. HRMS (ESI+): calcd d = 7.55–7.47 (m, 2H, ArCH), 7.37–7.31 (m, 3H, ArCH), 5.48 (d,
4
3
5
for C14H19BrNaO9 [M + Na]+ 433.0110; found 433.0113.
J = 10.1 Hz, 1H, CH), 5.31–5.24 (m, 2H, CH, CH), 5.05 (td,
6
(3R,4S,5R,E)-6-Bromo-2-(tert-butyldiphenylsilyloxyimino)-hexane- J = 4.6, 6.5 Hz, 1H, CH), 4.08 (d of AB system, J = 11.6 Hz, 1H,
1,3,4,5-tetrayl tetraacetate (9). To a solution of bromoketone 8 8CH2), 3.95 (d of AB system, J = 11.6 Hz, 1H, CH2), 3.60 (dd o
8
(3.06 g, 7.44 mmol) in toluene (150 mL), MgSO4 (25.5 g), O-tert- f ABX system, J = 4.5, 13.4 Hz, 1H, 7CH2), 3.39 (dd of ABX system,
butyldiphenylsilyl hydroxylamine (2.42 g, 8.93 mmol) and J = 6.5, 13.4 Hz, 1H, 7CH2), 2.08 (s, 3H, AcCH3), 2.06 (s, 3H, AcCH3),
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018
New J. Chem.

View Article Online
Paper
NJC
1.99 (s, 3H, AcCH3), 1.86 (s, 3H, AcCH3) ppm. 13C NMR (100 MHz, 1230, 1031 cmꢁ1. Major diastereoisomer: 1H NMR (400 MHz,
CDCl3) d = 170.8 (AcCO), 170.1 (AcCO), 170.0 (AcCO), 169.6 (AcCO), CDCl3) d = 5.44 (d, J = 10.4 Hz, 1H, 4CH), 5.30–5.21 (m, 1H, 5CH),
157.0 (2Cq), 130.1 (ArCH), 128.6 (ArCH), 127.8 (ArCq), 126.0 (ArCH), 5.13–5.05 (m, 1H, 6CH), 4.97 (s, 1H, 3CH), 3.96 (d of AB system,
8
91.7 (3CH), 74.7 (3aCq), 73.0 (5CH), 69.9 (6CH), 67.9 (4CH), 64.4 J = 11.6 Hz, 1H, CH2), 3.75 (d of AB system, J = 11.6 Hz, 1H,
(8CH2), 53.1 (7CH2), 20.9 (AcCH3), 20.8 (AcCH3), 20.8 (AcCH3), 20.7 8CH2), 3.52 (dd of ABX system, J = 5.0, 13.2 Hz, 1H, 7CH2), 3.20
8
4
(AcCH3) ppm. NOESY correlation between CH2 and CH. Minor (dd of ABX system, J = 6.4, 13.2 Hz, 1H, 7CH2), 2.09 (s, 3H,
diastereoisomer significative signals: 1H NMR (400 MHz, CDCl3) AcCH3), 2.06 (s, 3H, AcCH3), 2.03 (s, 3H, AcCH3), 2.01 (s, 3H,
0
0
0
d = 5.41–5.36 (m, 1H, 5 CH), 5.22–5.16 (m, 2H, 3 CH, 6 CH), 4.23 (d AcCH3), 0.22 (s, 9H, TMSCH3) ppm. 13C NMR (100 MHz, CDCl3)
0
of AB system, J = 11.4, 1H, 8 CH2), 4.19 (d of AB system, J = 11.2, d = 170.8 (AcCO), 170.2 (AcCO), 170.0 (AcCO), 169.6 (AcCO), 162.6
0
0
1H, 8 CH2), 3.69 (dd, of ABX system, J = 4.8, 14.3 Hz, 1H, 7 CH2), (2Cq), 106.1 (3CH), 73.4 (3aCq), 72.4 (5CH), 69.9 (6CH), 67.7 (4CH),
0
3.33 (dd of ABX system, J = 7.7, 14.3 Hz, 1H, 7 CH2), 2.09 (s, 3H, 64.8 (8CH2), 53.2 (7CH2), 21.0 (AcCH3), 20.9 (AcCH3), 20.8 (AcCH3),
AcCH3), 2.05 (s, 3H, AcCH3), 2.00 (s, 3H, AcCH3) ppm. 13C NMR 20.7 (AcCH3), ꢁ2.3 (TMSCH3) ppm. NOESY correlation between
(100 MHz, CDCl3) d = 170.6 (AcCO), 170.2 (AcCO), 169.7 (AcCO), 8CH2 and 4CH. Minor diastereoisomer significative signals:
0
0
169.6 (AcCO), 156.0 (2 Cq), 130.0 (ArCH), 127.5 (ArCq), 126.1 (ArCH), 1H NMR (400 MHz, CDCl3) d = 4.88 (s, 1H, 3 CH), 4.12 (d
0
0
0
0
0
0
94.7 (3 CH), 73.4 (3a Cq), 72.3 (4 CH), 71.8 (5 CH), 68.5 (6 CH), 65.6 of AB system, J = 11.1 Hz, 1H, 8 CH2), 4.00 (d of AB system,
0
0
0
0
(8 CH2), 52.4 (7 CH2), 21.1 (AcCH3), 21.1 (AcCH3), 21.0 (AcCH3), 20.9 J = 11.1 Hz, 1H, 8 CH2), 3.46 (dd, J = 4.6, 14.3 Hz, 1H, 7 CH2), 3.26
0
0
0
(AcCH3) ppm. NOESY correlation between 8 CH2 and 5 CH. HRMS (dd, J = 8.2, 14.3 Hz, 1H, 7 CH2), 0.21 (s, 9H, TMSCH3) ppm.
(ESI+): calcd for C22H26NO9 [M + H]+ 448.1608; found 448.1608. 13C NMR (100 MHz, CDCl3) d = 170.6 (AcCO), 170.2 (AcCO),
0
0
0
0
(3aR,4R,5R,6S)-3a-(Acetoxymethyl)-2-cyclohexyl-3a,4,6,7-tetra- 169.4 (AcCO), 161.9 (2 Cq), 108.4 (3 CH), 73.0 (5 CH), 71.8 (3a Cq),
0
0
0
0
hydro-5H-isoxazolo[2,3-a]pyridine-4,5,6-triyl triacetate (10b). A 71.3 (6 CH), 68.2 (4 CH), 66.2 (8 CH2), 52.3 (7 CH2), 21.0 (AcCH3),
mixture of nitrone 4 (44 mg, 0.13 mmol) and cyclohexylacetylene 21.0 (AcCH3), ꢁ0.18 (TMSCH3) ppm. HRMS (ESI+): calcd for
(0.5 mL, 3.7 mmol) was stirred at room temperature for 4 days. C19H30NO9Si [M + H]+ 444.1690; found 444.1699.
After concentration under reduced pressure, the residue was
(3aR,4R,5R,6S)-3a-Bis(acetoxymethyl)-3a,4,6,7-tetrahydro-5H-
purified by column chromatography over silica gel (pentane/ isoxazolo[2,3-a]pyridine-4,5,6-triyl triacetate (10d). A mixture
EtOAc 9 : 1) to give cycloadducts 10b and 100b (45 mg, 78%) as a of nitrone 4 (98 mg, 0.28 mmol) and prop-2-yn-1-yl acetate
colourless oil (mixture of diasteroisomers, dr = 9 : 1). IR n = 2933, (0.15 mL, 1.5 mmol) was stirred at room temperature for 2 days.
2855, 1742, 1668, 1450, 1368, 1215, 1033 cmꢁ1. Major diastereo- After concentration under reduced pressure, the crude product
1
isomer: H NMR (400 MHz, CDCl3) d = 5.32 (d, J = 10.5 Hz, 1H, was purified by column chromatography over silica gel (pentane/
5
6
4CH), 5.29–5.21 (m, 1H, CH), 5.02 (dd, J = 5.8, 12.0, 1H, CH), EtOAc 7 : 3) to give cycloadducts 10d and 100d (115 mg, 92%) as a
3
8
4.46 (s, 1H, CH), 3.90 (d of AB system, J = 11.6 Hz, 1H, CH2), colourless oil (mixture of diastereoisomers, dr = 4 : 1). IR n =3054,
3.76 (d of AB system, J = 11.6 Hz, 1H, CH2), 3.45 (dd of ABX 29570, 1740, 1431, 1372, 1213, 1033 cmꢁ1. Major diastereo-
8
system, J = 4.9, 13.4 Hz, 1H, 7CH2), 3.21 (dd of ABX system, J = 6.0, isomer: 1H NMR (500 MHz, CDCl3) d = 5.40 (d, J = 10.3 Hz,
13.4 Hz, 1H, 7CH2), 2.15–2.05 (m, 1 H, CyCH), 2.03 (s, 3H, AcCH3), 1H, 4CH), 5.27 (dd, J = 6.8, 10.2 Hz, 1H, 5CH), 5.11–5.06 (m, 1H,
1.98 (s, 3H, AcCH3), 1.98 (s, 3H, AcCH3), 1.95 (s, 3H, AcCH3), 6CH), 4.94 (s, 1H, 3CH), 4.66 (br s, 2H, 9CH2), 4.01 (d of AB
1.91–1.57 (m, 6H, CyCH2), 1.31–1.15 (m, 4H, CyCH2) ppm. 13C system, J = 11.6 Hz, 1H, 8CH2), 3.91 (d of AB system, J = 11.6 Hz,
8
7
NMR (100 MHz, CDCl3) d = 170.6 (AcCO), 170.0 (AcCO), 169.9 1H, CH2), 3.54 (dd of ABX system, J = 4.9, 13.8 Hz, 1H, CH2),
(AcCO), 169.4(nAcCO), 164.1 (2Cq), 89.6 (3CH), 73.6 (3aCq), 72.3 3.35 (dd of ABX system, J = 5.7, 13.8 Hz, 1H, CH2), 2.13 (s, 3H,
7
(5CH), 70.1 (4CH), 67.7 (6CH), 64.9 (8CH2), 53.1 (7CH2), 35.6 AcCH3), 2.10 (s, 3H, AcCH3), 2.06 (s, 3H, AcCH3), 2.06 (s, 3H,
(CyCH), 30.6 (CyCH2), 30.3 (CyCH2), 25.9 (CyCH2), 25.7 (CyCH2), AcCH3), 2.02 (s, 3H, AcCH3) ppm. 13C NMR (125 MHz, CDCl3)
25.6 (CyCH2), 20.8 (AcCH3), 20.8 (AcCH3), 20.7 (AcCH3), 20.5 d = 170.8 (AcCO), 170.3 (AcCO), 170.2 (AcCO), 169.7 (AcCO), 169.6
(AcCH3) ppm. NOESY correlation between 8CH2 and 4CH. Minor (AcCO), 154.1 (2Cq), 96.4 (3CH), 74.1 (3aCq), 72.5 (5CH), 70.5 (6CH),
diastereoisomer significative signals: 1H NMR (400 MHz, CDCl3) 67.7 (4CH), 64.8 (8CH2), 56.9 (9CH2), 53.3 (7CH2), 21.1 (AcCH3),
0
0
d = 5.15–5.09 (m, 1H, 6 CH), 4.38 (s, 1H, 3 CH) ppm. 13C NMR 21.0 (AcCH3), 20.9 (AcCH3), 20.9 (AcCH3), 20.8 (AcCH3) ppm.
(100 MHz, CDCl3) d = 170.4 (AcCO), 170.1 (AcCO), 169.5 (AcCO), NOESY correlation between 8CH2 and 4CH. Minor diastereo-
0
0
0
0
169.3 (AcCO), 163.3 (2 Cq), 92.3 (3 CH), 72.7 (5 CH), 71.7 (4 CH), isomer significative signals: 1H NMR (500 MHz, CDCl3) d = 5.21
0
0
0
0
0
68.1 (6 CH), 66.0 (8 CH2), 52.2 (7 CH2), 35.3 (CyCH), 30.4 (CyCH2), (d, J = 5.9 Hz, 1H, 4 CH), 5.19–5.16 (m, 1H, 6 CH), 4.91 (s, 1H,
0
0
30.4 (CyCH2) ppm. HRMS (ESI+): calcd for C22H32NO9 [M + H]+ 3 CH), 4.71 (d of AB system, J = 13.5, 1H, 9 CH2), 4.58 (d of
0
454.2077; found 454.2072.
AB system, J = 13.5, 1H, 9 CH2), 4.17 (d of AB system, J = 11.2 Hz,
0
0
(3aR,4R,5R,6S)-3a-(Acetoxymethyl)-2-(trimethylsilyl)-3a,4,6,7- 1H, 8 CH2), 4.12 (d of AB system, J = 11.2 Hz, 1H, 8 CH2), 3.57 (dd
0
tetrahydro-5H-isoxazolo[2,3-a]pyridine-4,5,6-triyl triacetate (10c). of ABX system, J = 4.6, 14.5 Hz, 1H, 7 CH2), 3.28 (dd of ABX
0
Nitrone 4 (204 mg, 0.59 mmol) and trimethylsilylacetylene (1.6 mL, system, J = 8.7, 14.5 Hz, 1H, 7 CH2), 2.11 (s, 3H, AcCH3), 2.11
11.2 mmol) were dissolved in CH2Cl2 (1.5 mL) and stirred at room (s, 3H, AcCH3), 2.08 (s, 3H, AcCH3), 2.07 (s, 3H, AcCH3) ppm.
temperature for 2 days. After concentration under reduced 13C NMR (125 MHz, CDCl3) d = 170.6 (AcCO), 170.5 (AcCO), 170.2
0
0
pressure, the crude product was purified on silica gel (CH2Cl2) (AcCO), 169.8 (AcCO), 169.4 (AcCO), 153.3 (2 Cq), 99.6 (3 CH), 72.7
0
0
0
0
0
to afford cycloadducts 10c and 100c (253 mg, 97%) as a yellow oil (5 CH), 71.5 (4 CH), 67.9 (6 CH), 65.8 (8 CH2), 56.5 (9 CH2),
0
(mixture of diastereoisomers, dr = 9 : 1). IR n = 2962, 1741, 1367, 52.4 (7 CH2), 21.2 (AcCH3), 21.1 (AcCH3), 21.1 (AcCH3), 20.9 (AcCH3)
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018

View Article Online
NJC
Paper
ppm. HRMS calcd for C19H25NO11 [M + H]+ 444.1500; found d = 170.7 (AcCO), 170.5 (AcCO), 170.2 (AcCO), 170.2 (AcCO),
444.1495.
160.0 (2Cq), 92.7 (3CH), 74.7 (3aCq), 73.0 (5CH), 72.0 (6CH), 68.8
(3aR,4R,5R,6S)-3a-(Acetoxymethyl)-2-propyl-3a,4,6,7-tetrahydro- (4CH), 66.3 (8CH2), 53.9 (7CH2), 29.7 (10CH2), 26.5 (9CH2), 23.0
5H-isoxazolo[2,3-a]pyridine-4,5,6-triyl triacetate (10e). Nitrone 4 (11CH2), 20.9 (AcCH3), 20.8 (AcCH3), 20.7 (AcCH3), 20.7 (AcCH3),
(38 mg, 0.11 mmol) and 1-pentyne (165 mL, 1.67 mmol) were 14.2 (12CH3) ppm. Minor diastereoisomer significative signals:
0
disolved in CH2Cl2 (60 mL) and stirred at room temperature 1H NMR (500 MHz, (CD3)2CO) d = 5.30–5.25 (m, 1H, 5 CH), 5.22–
0
0
0
for 17 days. The reaction was monitored by TLC. When the 5.17 (m, 2H, 4 CH, 6 CH), 4.68 (s, 1H, 3 CH), 3.53 (dd of ABX
0
conversion of nitrone was completed, the mixture was concen- system, J = 4.6, 14.3 Hz, 1H, 7 CH2), 3.22 (dd of ABX system, J =
0
trated under reduced pressure. The diastereomeric cycloadducts 8.6, 14.4 Hz, 1H, 7 CH2), 2.00 (s, 3H, AcCH3), 2.00 (s, 3H, AcCH3),
10e and 100e (dr = 9 : 1) were obtained as a colourless oil. Note 1.98 (s, 3H, AcCH3), 1.97 (s, 3H, AcCH3) ppm. 13C NMR (125 MHz,
that these compounds are not stable and should be used (CD3)2CO) d = 170.6 (AcCO), 170.4 (AcCO), 170.0 (AcCO), 169.9
0
0
0
0
immediately in the next step. IR n = 2977, 2876, 1754, 1672, (AcCO), 159.3 (2 Cq), 96.0 (3 CH), 73.4 (5 CH), 72.6 (6 CH), 68.6
0
0
0
0
0
1432, 1362, 1225, 1056 cmꢁ1. Major diastereoisomer: H NMR (4 CH), 65.5 (8 CH2), 52.9 (7 CH2), 26.1 (9 CH2), 22.9 (11 CH2), 20.9
1
0
(500 MHz, (CD3)2CO) d = 5.38 (d, J = 10.5 Hz, 1H, 4CH), 5.37–5.32 (AcCH3), 20.8 (AcCH3), 14.1 (12 CH3) ppm. HRMS (ESI+): calcd for
(m, 1H, 5CH), 5.10–5.05 (m, 1H, 6CH), 4.67 (s, 1H, 3CH), 3.98 (d C20H30NO9 [M + H]+ 428.1915; found 428.1917.
of AB system, J = 11.4 Hz, 1H, 8CH2), 3.84 (d of AB system,
(3S,4R,5R)-3,4,5-Trihydroxy-6-(hydroxymethyl)-2,3,4,5-tetra-
J = 11.3 Hz, 1H, 8CH2), 3.63 (dd of ABX system, J = 5.1, 14.3 Hz, hydropyridine 1-oxide (5). Nitrone 4 (82 mg, 0.24 mmol) was
7
7
1H, CH2), 3.31 (dd of ABX system, J = 4.8, 14.3 Hz, 1H, CH2), dissolved in 3.0 mL of methanol saturated with ammonia. The
2.21–2.16 (m, 2H, 9CH2), 2.03 (br s, 6H, AcCH3), 1.99 (s, 3H, reaction mixture was stirred at room temperature for 30 minutes.
AcCH3), 1.96 (s, 3H, AcCH3), 1.64–1.53 (m, 2H, 10CH2), 1.00 (t, The solvent was evaporated under reduced pressure and the
J = 7.4 Hz, 11CH3) ppm. 13C NMR (125 MHz, (CD3)2CO) d = 170.6 residue was purified by chromatography (silica gel, CH2Cl2/
(AcCO), 170.4 (AcCO), 170.1 (AcCO), 170.1 (AcCO), 159.7 (2Cq), 92.8 MeOH 4 : 1) to afford 5 (35 mg, 81%) as a colourless oil. [a]D20
=
(3CH), 74.6 (3aCq), 72.9 (5CH), 71.9 (6CH), 68.7 (4CH), 66.2 ꢁ49.2 (c, 0.16, MeOH). IR n = 3253, 2904, 1616, 1426, 1160,
(8CH2), 53.8 (7CH2), 28.7 (9CH2), 20.8 (AcCH3), 20.7 (10CH2), 1065, 1005 cmꢁ1. 1H NMR (500 MHz, CD3OD) d = 4.66 (d of AB
20.7 (AcCH3), 20.6 (AcCH3), 20.6 (AcCH3), 14.0 (11CH3) ppm. system, J = 16.6 Hz, 1H, 1CH2), 4.46 (d of AB system, J = 16.9 Hz,
NOESY correlation between 8CH2 and 4CH. Minor diastereo- 1H, 1CH2), 4.43–4.38 (m, 1H, 3CH), 4.08–3.98 (m, 2H, 5CH,
isomer significative signals: 1H NMR (500 MHz, (CD3)2CO) 6CH2), 3.89–3.82 (m, 1H, 4CH), 3.72 (br d of AB system, J = 13.1
0
0
0
d = 5.30–5.27 (m, 1H, 5 CH), 5.22–5.17 (m, 2H, 4 CH, 6 CH), Hz, 1H, 6CH2) ppm. 13C NMR (125 MHz, CD3OD) d = 153.3
0
0
4.69 (s, 1H, 3 CH), 4.08 (d of AB system, J = 11.1 Hz, 1H, 8 CH2), (2Cq), 70.7 (4CH), 69.8 (3CH), 68.0 (5CH), 62.6 (6CH2), 59.6
0
4.06 (d of AB system, J = 11.1 Hz, 1H, 8 CH2), 3.53 (dd of ABX (7CH2). HRMS (ESI+): calcd for C6H12NO5 [M + H]+ 178.0715;
0
system, J = 4.6, 14.3 Hz, 1H, 7 CH2), 3.22 (dd of ABX system, found 178.0716.
0
J = 8.6, 14.4 Hz, 1H, 7 CH2), 2.00 (s, 3H, AcCH3), 2.00 (s, 3H,
(3aR,4R,5R,6S)-3a-(Hydroxymethyl)-2-phenyl-3a,4,6,7-tetrahydro-
0
AcCH3), 0.97 (t, J = 7.4 Hz, 11 CH3) ppm. 13C NMR (125 MHz, 5H-isoxazolo[2,3-a]pyridine-4,5,6-triol (6a). Cycloadducts 10a and
0
0
0
0
(CD3)2CO) d = 96.1 (3 CH), 73.3 (5 CH), 72.6 (4 CH), 68.8 (6 CH), 100a (120 mg, 0.268 mmol) were dissolved in methanol saturated
0
0
0
0
66.6 (8 CH2), 52.8 (7 CH2), 28.3 (9 CH2), 13.9 (11 CH3) ppm. with ammonia (4 mL) and the solution was stirred at room
HRMS (ESI+): calcd for C19H28NO9 [M + H]+ 414.1764; found temperature. After 2 hours, the solvent was evaporated under
414.1760.
reduced pressure and the residue was purified by chromato-
(3aR,4R,5R,6S)-3a-(Acetoxymethyl)-2-butyl-3a,4,6,7-tetrahydro- graphy (silica gel, CH2Cl2/MeOH 4 : 1) to afford compounds 6a
5H-isoxazolo[2,3-a]pyridine-4,5,6-triyl triacetate (10f). Nitrone 4 and 6a0 (62 mg, 83%) as a white solid (dr = 4 : 1). By recrystalisation
(40 mg, 0.115 mmol) and 1-hexyne (0.2 mL, 1.73 mmol) were in methanol, iminosugar 6a (8 mg, 11%) was obtained as a single
dissolved in CH2Cl2 (60 mL) and stirred at room temperature for diastereoisomer. M.p. 123–125 1C. [a]2D0 = +42.0 (c 0.52, MeOH). IR
12 days. The reaction was monitored by TLC. When the conver- n = 3373, 2929, 2887, 1447, 1390, 1123, 1016 cmꢁ1 1H NMR
.
sion of nitrone was completed, the mixture was concentrated (500 MHz, CD3OD) d = 7.57–7.50 (m, 2H, ArCH), 7.40–7.31 (m, 3H,
under reduced pressure. The diastereomeric cycloadducts 10f ArCH), 5.53 (s, 1H, 3CH), 3.92 (d, J = 8.8 Hz, 1H, 4CH), 3.56 (d of AB
and 100f (dr = 9 :1) were obtained as a colourless oil. Note that system, J = 11.2 Hz, 1H, 8CH2), 3.47 (dd, J = 2.7, 10.0 Hz, 1H, 7CH2),
these compounds are not stable and should be used immediately 3.42–3.38 (m, 2H, 5CH, 6CH), 3.36 (d of AB system, J = 11.3 Hz, 1H,
in the next step. IR n = 2955, 2927, 2866, 1758, 1679, 1435, 1369, 8CH2), 2.91–2.83 (m, 1H, 7CH2) ppm. 13C NMR (125 MHz, CD3OD)
1230, 1024 cmꢁ1. Major diastereoisomer: 1H NMR (500 MHz, d = 156.3 (2Cq), 130.4 (ArCq), 130.4 (ArCH), 129.5 (ArCH), 126.6
4
(CD3)2CO) d = 5.38 (d, J = 10.6 Hz, 1H, CH), 5.36–5.32 (m, 1H, (ArCH), 96.4 (3CH), 79.6 (3aCq), 77.4 (5CH), 70.5 (4CH), 67.7 (6CH),
8
5CH), 5.07 (td, J = 5.0, 6.4 Hz, 1H, 6CH), 4.66 (s, 1H, 3CH), 3.98 (d 63.8 (8CH2), 57.6 (7CH2) ppm. NOESY correlation between CH2
4
of AB system, J = 11.4 Hz, 1H, 8CH2), 3.84 (d of AB system, J = 11.4 and CH. HRMS (ESI+): calcd for C14H18NO5 [M + H]+ 280.1185;
Hz, 1H, 8CH2), 3.63 (dd of ABX system, J = 5.1, 14.3 Hz, 1H, 7CH2), found 280.1185.
3.31 (dd of ABX system, J = 4.7, 14.3 Hz, 1H, 7CH2), 2.27–2.15 (m,
(3aR,4R,5R,6S)-2-Cyclohexyl-3a-(hydroxymethyl)-3a,4,6,7-tetra-
2H, 9CH2), 2.03 (br s, 6H, AcCH3), 1.99 (s, 3H, AcCH3), 1.96 (s, 3H, hydro-5H-isoxazolo[2,3-a]pyridine-4,5,6-triol (6b). Cycloadducts
AcCH3), 1.60–1.38 (m, 2H, 10CH2), 1.47–1.38 (m, 2H, 11CH2), 10b and 100b (60 mg, 0.132 mmol) were dissolved in methanol
0.93 (t, J = 7.3 Hz, 12CH3) ppm. 13C NMR (125 MHz, (CD3)2CO) saturated with ammonia (3 mL) and the solution was stirred at
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018
New J. Chem.

View Article Online
Paper
NJC
7
9
room temperature. After 6 hours, the solvent was evaporated 8CH2), 2.84–2.77 (m, 1H, CH2), 2.14 (t, J = 7.3 Hz, 2H, CH2),
under reduced pressure and the residue was purified by chroma- 1.59–1.47 (m, 2H, 10CH2), 0.96 (t, J = 7.3 Hz, 3H, 11CH3) ppm. 13
C
tography (silica gel, CH2Cl2/MeOH 4: 1) to afford 6b and 60b NMR (125 MHz, CD3OD) d = 158.9 (2Cq), 95.8 (3CH), 78.7 (3aCq),
(22 mg, 58%) as a colourless oil (dr = 9 : 1). IR n = 3313, 2927, 77.2 (5CH), 70.4 (4CH), 67.7 (6CH), 64.1 (8CH2), 57.6 (7CH2), 29.3
2857, 1663, 1448, 1093, 1040, 1027 cmꢁ1. Major diastereoisomer: (9CH2), 21.1 (10CH2), 14.0 (11CH3) ppm. NOESY correlation
1H NMR (500 MHz, CD3OD) d = 4.72 (s, 1H, 3CH), 3.83 (d, between 8CH2 and 4CH. Minor diastereoisomer significative
J = 9.0 Hz, 1H, 4CH), 3.43 (d of AB system, J = 11.2 Hz, 1H, signals: 1H NMR (500 MHz, CD3OD) d = 3.80–3.64 (m,
0
0
0
0
5
6
8CH2), 3.36–3.28 (m, 3H, CH, CH, 7CH2), 3.19 (d of AB system, 5H, 4 CH, 5 CH, 6 CH, 8 CH2), 3.13 (dd, J = 8.5, 14.1 Hz, 1H,
0
0
J = 11.2 Hz, 1H, 8CH2), 2.82–2.74 (m, 1H, 7CH2), 2.16–2.06 (m, 1H, 7 CH2) ppm. 13C NMR (125 MHz, CD3OD) d = 157.5 (2 Cq), 100.2
0
0
0
0
0
CyCH), 1.92–1.15 (m, 10H, CyCH2) ppm. 13C NMR (125 MHz, (3 CH), 78.0 (5 CH), 76.6 (4 CH), 76.6 (3a Cq), 70.1 (6 CH),
0
0
0
0
CD3OD) d = 163.5 (2Cq), 93.7 (3CH), 78.5 (3aCq), 77.3 (5CH), 70.3 64.9 (8 CH2), 56.0 (7 CH2), 29.0 (9 CH2), 21.0 (10 CH2) ppm.
(4CH), 67.7 (6CH), 64.2 (8CH2), 57.4 (7CH2), 36.9 (CyCH), 31.8 HRMS (ESI+): calcd for C11H20NO5 [M + H]+ 246.1336; found
(CyCH2), 31.8 (CyCH2), 27.1 (CyCH2), 26.8 (CyCH2) ppm. NOESY 246.1337.
correlation between 8CH2 and 4CH. Minor diastereoisomer
(3aR,4R,5R,6S)-2-Butyl-3a-(hydroxymethyl)-3a,4,6,7-tetrahydro-
1
significative signals: H NMR (500 MHz, CD3OD) d = 3.80–3.63 5H-isoxazolo[2,3-a]pyridine-4,5,6-triol (6f). Cycloadducts 10f and
0
0
0
0
0
(m, 5H, 4 CH, 5 CH, 6 CH, 8 CH2), 3.15–3.09 (m, 1H, 7 CH2) ppm. 100f (43 mg, 0.1 mmol) were dissolved in methanol saturated
0
0
13C NMR (125 MHz, CD3OD) d = 77.9 (5 CH), 76.7 (4 CH), 70.1 with ammonia (2.5 mL) and the solution was stirred at room
0
0
0
(6 CH), 65.0 (8 CH2), 56.0 (7 CH2) ppm. HRMS (ESI+): calcd for temperature. After 5 hours, the solvent was evaporated under
C14H24NO5 [M + H]+ 286.1649; found 286.1653.
reduced pressure and the residue was purified by chromatography
(3aR,4R,5R,6S)-2,3a-bis(Hydroxymethyl)-3a,4,6,7-tetrahydro- (silica gel, CH2Cl2/MeOH 4 : 1) to afford 6f and 60f (25 mg, 83%) as
5H-isoxazolo[2,3-a]pyridine-4,5,6-triol (6d). Cycloadducts 10d a colourless oil (dr = 9 : 1). IR n = 3320, 2968, 2932, 2862, 1667,
and 100d (70 mg, 0.158 mmol) were dissolved in methanol 1152, 1039, 1002 cmꢁ1. Major diastereoisomer: 1H NMR (500 MHz,
saturated with ammonia (2.5 mL) and the solution was stirred CD3OD) d = 4.75 (s, 1H, 3CH), 3.83 (d, J = 8.6 Hz, 1H, 4CH), 3.44 (d
at room temperature. After 2.5 hours, the solvent was evaporated of AB system, J = 11.3 Hz, 1H, 8CH2), 3.37–3.32 (m, 3H, 5CH, 6CH,
under reduced pressure and the residue was purified by chromato- 7CH2), 3.22 (d of AB system, J = 11.2 Hz, 1H, 8CH2), 2.85–2.75 (m,
graphy (silica gel, CH2Cl2/MeOH 4 : 1) to afford 6d and 60d (27 mg, 1H, 7CH2), 2.22–2.10 (m, 2H, 9CH2), 1.54–1.44 (m, 2H, 10CH2),
73%) as a yellow oil (dr = 4 : 1). IR n = 3304, 2923, 2868, 1671, 1421, 1.43–1.33 (m, 2H, 11CH2), 0.92 (t, J = 7.3 Hz, 3H, 12CH3) ppm. 13
C
1102, 1015 cmꢁ1. Major diastereoisomer: 1H NMR (500 MHz, NMR (125 MHz, CD3OD) d = 159.1 (2Cq), 95.6 (3CH), 78.7 (3aCq),
3
CD3OD) d = 5.01 (s, 1H, CH), 4.12 (d of AB system, J = 14.3 Hz, 77.2 (5CH), 70.4 (4CH), 67.7 (6CH), 64.1 (8CH2), 57.6 (7CH2), 30.0
1H, 9CH2), 4.08 (d of AB system, J = 14.3 Hz, 1H, 9CH2), 3.84 (d, (9CH2), 27.0 (10CH2), 23.3 (11CH2), 14.1 (12CH3) ppm. NOESY
J = 8.9 Hz, 1H, 4CH), 3.47 (d of AB system, J = 11.2 Hz, 1H, 8CH2), correlation between 8CH2 and 4CH. Minor diastereoisomer
1
3.39–3.33 (m, 3H, 5CH, 6CH, 7CH2), 3.27 (d of AB system, significative signals: H NMR (500 MHz, CD3OD) d = 3.80–3.64
0
0
0
0
J = 11.2 Hz, 1H, 8CH2), 2.90–2.83 (m, 1H, 7CH2) ppm. 13C (m, 5H, 4 CH, 5 CH, 6 CH, 8 CH2), 3.13 (dd, J = 8.4, 14.1 Hz, 1H,
0
0
NMR (125 MHz, CD3OD) d = 158.2 (2Cq), 97.7 (3CH), 78.6 7 CH2) ppm. 13C NMR (125 MHz, CD3OD) d = 157.7 (2 Cq), 100.0
0
0
0
0
0
(3aCq), 77.2 (5CH), 70.3 (4CH), 67.9 (6CH), 64.0 (8CH2), 57.5 (3 CH), 77.5 (5 CH), 75.6 (4 CH), 70.1 (6 CH), 64.9 (8 CH2), 56.0
0
0
0
(7CH2), 56.8 (9CH2) ppm. Minor diastereoisomer significative (7 CH2), 29.9 (9 CH2), 26.6 (10 CH2) ppm. HRMS (ESI+): calcd for
0
signals: 1H NMR (500 MHz, CD3OD) d = 5.00 (s, 1H, 3 CH), 4.08 C12H21NO5Na [M + H]+ 282.1312; found 282.1310.
9
(d of AB system, J = 14.5 Hz, 1H, CH2), 4.05 (d of AB system,
0
0
0
J = 14.5 Hz, 1H, 9CH2), 3.82–3.66 (m, 5H, 4 CH, 5 CH, 6 CH,
0
0
8 CH2), 3.16 (dd, J = 8.6, 14.1 Hz, 1H, 7 CH2) ppm. 13C NMR (125
Conflicts of interest
0
0
0
MHz, CD3OD) d = 101.8 (3 CH), 77.5 (5 CH), 76.7 (4 CH), 75.6
0
0
0
0
0
There are no conflicts to declare.
(
3a Cq), 70.0 (6 CH), 64.7 (8 CH2), 56.6 (9 CH2), 56.0 (7 CH2) ppm.
HRMS (ESI+): calcd for C9H16NO6 [M + H]+ 234.0972; found
234.0973.
Acknowledgements
(3aR,4R,5R,6S)-3a-(Hydroxymethyl)-2-propyl-3a,4,6,7-tetrahydro-
´
5H-isoxazolo[2,3-a]pyridine-4,5,6-triol (6e). Cycloadducts 10e and We thank Pr A. Martel (Universite du Maine, Le Mans) for
100e (44 mg, 0.106 mmol) were disolved in methanol saturated helpful discussions on DFT calculations. This work is sup-
´
with ammonia (2 mL) and the solution was stirred at room ported by the CNRS, the Universite Grenoble Alpes, and by
temperature. After 5 hours, the solvent was evaporated under the French National Research Agency in the framework of the
reduced pressure and the residue was purified by chromato- ‘‘Investissements d’avenir’’ program Glyco@Alps (ANR-15-
graphy (silica gel, CH2Cl2/MeOH 4 : 1) to afford 6e and 60e IDEX-02) and of the Labex ARCANE program (ANR-11-LABX-
(23 mg, 85%) as a colourless oil (dr = 9 : 1). IR n = 3341, 1651, 0003-01). S. T. is grateful to Campus France for an ‘‘Excellence
1
1466, 1433, 1102, 1017 cmꢁ1. Major diastereoisomer: H NMR Doctoral Fellowship’’. We also acknowledge support from the
(500 MHz, CD3OD) d = 4.76 (s, 1H, 3CH), 3.83 (d, J = 9.0 Hz, 1H, ICMG Chemistry Nanobio Platform (FR 2607), Grenoble,
4CH), 3.44 (d of AB system, J = 11.2 Hz, 1H, 8CH2), 3.37–3.33 (m, through which crystallographic, NMR and MS analyses have
3H, 5CH, 6CH, 7CH2), 3.22 (d of AB system, J = 11.2 Hz, 1H, been performed.
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018

View Article Online
NJC
Paper
13 (a) J. C. Battaro, C. D. Bedford and A. Dodge, Synth. Commun.,
1985, 15, 133–135; (b) S. E. Denmark, M. S. Dappen, N. L. Sear
and R. T. Jacobs, J. Am. Chem. Soc., 1990, 112, 3466–3474.
14 J. H. Clark, J. Chem. Soc., Chem. Commun., 1978, 789–791.
15 See Supporting Information for X-ray diffraction data;
CCDC 1587933 (for 4) contains the supplementary crystal-
lographic data for this paper†.
Notes and references
1 (a) J. Revuelta, S. Cicchi, A. Goti and A. Brandi, Synthesis,
2007, 485–504; (b) E.-L. Tsou, Y.-T. Yeh, P.-H. Liang and
W.-C. Cheng, Tetrahedron, 2009, 65, 93–100; (c) W.-B. Wang,
M.-H. Huang, Y.-X. Li, P.-X. Rui, X.-G. Hu, W. Zhang,
J.-K. Su, Z.-L. Zhang, J.-S. Zhu, W.-H. Xu, X.-Q. Xie, Y.-M. Jia
and C.-Y. Yu, Synlett, 2010, 488–492; (d) Y.-F. Chang, C.-W. Guo,
T.-H. Chan, Y.-W. Pan, E.-L. Tsou and W.-C. Cheng, Mol.
Diversity, 2011, 15, 203–214; (e) W.-B. Zhao, S. Nakagawa,
A. Kato, I. Adachi, Y.-M. Jia, X.-G. Hu, G. W. J. Fleet, F. X.
Wilson, G. Horne, A. Yoshihara, K. Izumori and C.-Y. Yu, J. Org.
Chem., 2013, 78, 3208–3221; ( f ) J.-S. Zhu, S. Nakagawa, W. Chen,
I. Adachi, Y.-M. Jia, X.-G. Hu, G. W. J. Fleet, F. X. Wilson,
T. Nitoda, G. Horne, R. vanWell, A. Kato and C.-Y. Yu, J. Org.
Chem., 2013, 78, 10298–10309; (g) D. Martella, G. D’Adamio,
C. Parmeggiani, F. Cardona, E. Moreno-Clavijo, I. Robina and
A. Goti, Eur. J. Org. Chem., 2016, 1588–1598.
2 (a) Iminosugars: From synthesis to therapeutic applications,
ed. P. Compain and O. R. Martin, John Wiley & Sons, Chichester,
England, 2007; (b) B. G. Winchester, Tetrahedron: Asymmetry,
2009, 20, 645–651; (c) R. J. Nash, A. Kato, C.-Y. Yu and G. W. J.
Fleet, Future Med. Chem., 2011, 3, 1513–1521; (d) G. Horne,
F. X. Wilson, J. Tinsley, D. H. Williams and R. Storer, Drug
Discovery Today, 2011, 16, 107–118; (e) N. F. Bras, N. M. F. S. A.
Cerqueira, J. Ramos and P. A. Fernandes, Expert Opin. Ther.
Pat., 2014, 24, 857–874.
3 E. Racine, C. Bello, S. Gerber-Lemaire, P. Vogel and S. Py,
J. Org. Chem., 2009, 74, 1766–1769.
4 J. Boisson, A. Thomasset, E. Racine, P. Cividino, T. Banchelin
Sainte-Luce, J.-F. Poisson, J.-B. Behr and S. Py, Org. Lett., 2015,
17, 3662–3665.
5 A. Vieira Da Cruz, A. Kanazawa, J.-F. Poisson, J.-B. Behr and
S. Py, J. Org. Chem., 2017, 82, 9866–9872.
6 (a) P.-Z. Zhang, X.-L. Li, H. Chen, Y.-N. Li and R. Wang,
Tetrahedron Lett., 2007, 48, 7813–7816; (b) P. Zhang, C. Wei,
E. Wang, W. Wang, M. Liu, Q. Yin, H. Chen, K. Wang, X. Li
and J. Zhang, Carbohydr. Res., 2012, 351, 7–16.
16 (a) R. J. Woods, C. W. Andrews and J. P. Bowen, J. Am. Chem.
´
Soc., 1992, 114, 859–864; (b) M. Miljkovic, D. Yeagley,
P. Deslongchamps and Y. L. Dory, J. Org. Chem., 1997, 62,
7597–7604.
17 Calculations were performed on the Gaussian suite of
programs: M. J. Frisch, G. W. Trucks, H. B. Schlegel,
G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani,
V. Barone, B. Mennucci, G. A. Petersson, et al., Gaussian 09,
revision 4.2.0, Gaussian, Inc., Wallingford, CT, 2009. See
ESI† for complete citation and results.
18 For cycloaddition reactions of the benzylated nitrone 1, see:
S. Tangara, C. Aupic, A. Kanazawa, J.-F. Poisson and S. Py,
Org. Lett., 2017, 19, 4842–4845.
19 (a) J. A. C. Romero, S. A. Tabacco and K. A. Woerpel, J. Am. Chem.
Soc., 2000, 122, 168–169; (b) S. Chamberland, J. W. Ziller and
K. A. Woerpel, J. Am. Chem. Soc., 2005, 127, 5322–5323.
20 R. V. Stevens, Acc. Chem. Res., 1984, 17, 289–296.
21 (a) A. Brandi, F. Cardona, S. Cicchi, F. M. Cordero and
A. Goti, Chem. – Eur. J., 2009, 15, 7808–7821; (b) A. Brandi,
F. Cardona, S. Cicchi, F. M. Cordero and A. Goti, Org. React.,
John Wiley & Sons, Inc., Hoboken, NJ, USA, 2017, pp. 1–321.
22 (a) D. François, A. Maden and W. V. Murray, Org. Lett., 2004, 6,
1931–1934; (b) A. Siriwardena, D. P. Sonawane, O. P. Bande,
P. R. Markad, S. Yonekawa, M. B. Tropak, S. Ghosh, B. A.
Chopade, D. J. Mahuran and D. D. Dhavale, J. Org. Chem.,
2014, 79, 4398–4404.
23 L. A. G. van den Broek, Tetrahedron, 1996, 52, 4467–4478.
24 A. Peer and A. Vasella, Helv. Chim. Acta, 1999, 82, 1044–1065.
25 J. F. Sproviero, A. Salinas and E. S. Bertiche, Carbohydr. Res.,
1971, 19, 81–86.
26 D. Gossan, A. Alabdul Magid, P. Kouassi-Yao, J.-B. Behr,
A. Ahibo, L. Djakoure, D. Harakat and L. Voutquenne-
Nazabadioko, Phytochemistry, 2015, 109, 76–83.
7 S. Desvergnes, Y. Vallee and S. Py, Org. Lett., 2008, 10,
2967–2970.
8 (a) J. Golik, H. Wong, B. Krishnan, D. M. Vyas and T. W. Doyle,
Tetrahedron Lett., 1991, 32, 1851–1854; (b) E. Racine, O. L.
Burchak and S. Py, Eur. J. Org. Chem., 2016, 4003–4012.
9 (a) H. H. Schlubach and G. Graefe, Liebigs Ann. Chem., 1937,
532, 211–227; (b) F. W. Lichtenthaler, Carbohydr. Res., 1998,
313, 69–89.
10 M. C. Teglia and R. A. Cadenas, Carbohydr. Res., 1971, 19,
223–230.
11 F. Chery, L. Cronin, J. L. O’Brien and P. V. Murphy, Tetrahedron,
2004, 60, 6597–6608.
27 (a) M. Malinowski, T. Rowicki, P. Guzik, M. Wielechowska,
A. Sobiepanek and W. Sas, Eur. J. Org. Chem., 2016, 3642–3649;
`
´
(b) Y. Brissonnet, S. Ladeveze, D. Teze, E. Fabre, D. Deniaud,
ˇ
´
F. Daligault, C. Tellier, S. Sestak, M. Remaud-Simeon, G. Potocki-
Veronese and S. G. Gouin, Bioconjugate Chem., 2015, 26, 766–772;
(c) M. Sandbhor, M. Bhasin, D. T. Williams, M. Hsieh, S.-H. Wub
and W. Zou, Carbohydr. Res., 2008, 343, 2878–2886.
28 (a) T. Matsuzawa and K. Yaoi, Appl. Microbiol. Biotechnol., 2017,
101, 633–646; (b) A. V. Samoshin, I. A. Dotsenko, N. M. Samoshina,
A. H. Franz and V. V. Samoshin, Int. J. Carbohydr. Chem., 2014,
941059/1; (c) Y. Nakagawa, S. Sehata, S. Fujii, H. Yamamoto,
A. Tsuda and K. Koumoto, Tetrahedron, 2014, 70, 5895–5903.
12 G. Pistia and R. I. Hollingsworth, Carbohydr. Res., 2000, 328,
467–472.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018
New J. Chem.