Synthesis and NMR spectroscopic analysis of 3-nitro-pyranoside, 3-nitro-septanoside and 4-nitro-septanoside derivatives by condensation of the anion of nitromethane with glycoside dialdehydes

Article abstract of DOI:10.1016/j.tetasy.2009.08.004

The utility of the nitroaldol reaction for accessing 3-nitro-pyranoside, 3-nitro-septanoside or 4-nitro-septanoside derivatives, by reaction of the anion of nitromethane with glycoside dialdehydes is demonstrated. Initially, the feasibility of using unpro

Full text of DOI:10.1016/j.tetasy.2009.08.004

Tetrahedron: Asymmetry 20 (2009) 2162–2166
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis and NMR spectroscopic analysis of 3-nitro-pyranoside,
3-nitro-septanoside and 4-nitro-septanoside derivatives by condensation
of the anion of nitromethane with glycoside dialdehydes
b
Helen M. I. Osborn a, , Andrea Turkson
*
a Reading School of Pharmacy, University of Reading, Whiteknights, Reading RG6 6AD, UK
b Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The utility of the nitroaldol reaction for accessing 3-nitro-pyranoside, 3-nitro-septanoside or 4-nitro-
septanoside derivatives, by reaction of the anion of nitromethane with glycoside dialdehydes is demon-
strated. Initially, the feasibility of using unprotected glucoside dialdehydes was probed for the synthesis
of the septanoside products, but this afforded pyranoside rather than septanoside targets. Subsequent
studies utilised protected glycoside dialdehydes within the methodology, which allowed entry into a
range of 3-nitro or 4-nitro-septanosides in good yield. NMR spectroscopic analysis allowed determination
of the stereochemistry of each of the products thus afforded.
Received 17 July 2009
Accepted 4 August 2009
Available online 31 August 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
In recent years, the development of carbohydrate analogues as
potential drug targets has received intense interest due to the
increasing knowledge of the roles of carbohydrates in biological
and disease processes.1 Whilst the synthesis of pyranoside and
furanoside derivatives has been widely reported in the literature,2
the synthesis of septanoside derivatives has been less commonly
reported. However, since some seven-membered carbohydrate
analogues have received interest for their therapeutic potential,3,4
and septanoses may be able to adopt distorted conformations in
glyco-enzyme binding sites,5 their synthesis is gaining increased
attention.6 Of direct relevance to this study is the preparation of
3-nitroseptanosides via the nitroaldol reaction of the anion of
nitromethane with glycoside dialdehydes; this a reaction we have
reinvestigated and extended in this programme of work.7
At the outset of this study, benzyl-b-D-glucopyranoside 1 was
used as the substrate for the oxidative cleavage reactions, to afford
the unprotected dialdehydes required for the nitro aldol reaction.
Given the potential for the formation of complex mixtures of regio-
and stereoisomeric products from the nitroaldol reaction, the use
of the UV active substrate benzyl-b-D-glucopyranoside 1 was con-
sidered prudent, in order to allow facile monitoring of mixtures
through TLC analysis. As shown in Scheme 1, the glucopyranoside
was treated with 1.2 equiv of sodium periodate at low temperature
for short reaction times, in order to access dialdehyde 2 resulting
from selective cleavage of the C-3,4 diol pair.8b This was then
reacted with 5 equiv of the anion of nitromethane, to potentially
furnish 4-nitroseptanoside 4. The analogous methyl-a-D-glucopy-
ranoside substrate was also used within the investigation as it
A number of researchers8 including ourselves have developed
methods that allow selective cleavage of specific diol pairs within
the carbohydrate framework. In previous work from our labora-
tory, we exploited this methodology to allow selective entry to
morpholines or oxazepanes, after reductive amination of the dial-
dehydes thus formed. Herein we extend this study to potentially
allow access to 4-nitro-septanosides, via nitroaldol reactions with
the dialdehydes thus formed, without the need for extensive pro-
tecting group strategies.
had previously been utilised within nitroaldol reactions.9
Despite much experimentation, it was not possible to access 4-
nitroseptanoside 4 using the unprotected substrates; instead in all
cases a complex mixture of products resulted, which could not be
separated. Analysis of the 1H NMR spectra of the crude mixtures
resulting from the study indicated that 3-nitro-pyranoside 5 was
always formed as one component of the reaction mixture. It was
not possible to ascertain whether nitroseptanosides had also been
prepared due to the complexity of the product distribution. More-
over, despite extensive experimentation, it did not prove possible
to optimise the methodology to bias formation of 4-nitroseptano-
side 4 using the unprotected glycoside substrate 1.
* Corresponding author. Fax: +44 (0)118 378 4644.
E-mail address: h.m.i.osborn@rdg.ac.uk (H.M.I. Osborn).
0957-4166/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2009.08.004

H. M. I. Osborn, A. Turkson / Tetrahedron: Asymmetry 20 (2009) 2162–2166
2163
OH
OH
OH
i)
ii)
O
O
O
HO
HO
O
O
OBn
OBn
OBn
O
OH
OH
O
3
2
1
iii)
iii)
OH
OH
OBn
O
O
HO
O2N
OBn
HO
OH
OH
O2N
OH
4
5
Scheme 1. Reagents and conditions: (i) NaIO4, 1.2 equiv; (ii) NaIO4, further 3.8 equiv; (iii) nitromethane, NaOMe, 5 equiv.
As 3-nitropyranoside 5 is of interest in its own right as a precur-
sor to an aminoglycoside, attempts were made to improve the
yield of its formation from the unprotected glycoside substrate 1.
Thus, tetraol 1 was treated with 5 equiv of NaIO4 for an extended
reaction time of 18 h to afford dialdehyde 3. This was then utilised
within the nitroaldol methodology under a range of conditions; the
best results were obtained upon treatment of the dialdehyde with
an excess of the anion of nitromethane, initially at ꢀ78 °C and then
at 5 °C, for 18 h. This allowed the synthesis of nitroaldol 5 in 31%
yield. This compares well with the yield of formation of 6, previ-
raphy to afford the products 13, 14 and 15 in good yields over two
steps, as indicated below in Table 1.
In all cases, NMR spectroscopic analysis was utilised to deter-
mine the stereochemistry of the targets formed. For 3-nitro-sept-
anoside 13, H-2 and H-3 shared
a large coupling constant
(10.5 Hz), whilst H-3 and H-4 displayed only a very small coupling
constant (2.5 Hz). Moreover, the NOE difference spectrum showed
that irradiation of H-3 enhanced the signals for H-4 and 5; like-
wise, the irradiation of H-5 enhanced the signals of H-3 and 4, sug-
gesting that these protons are on the same side of the ring. As a
result of these NMR spectroscopic studies, the product was as-
ously reported as a result of using methyl-a-D-glucopyranoside
within the oxidative cleavage methodology.9 NMR spectroscopic
analysis of 5 was utilised to determine the stereochemical features
of 5 and this illustrated that H-1 (d, J 8.0 Hz), H-2 (dd, J 8.0,
10.5 Hz) and H-3 (app. t, J 10.0 Hz) were of an axial–axial–axial ori-
entation, which suggests that the nitroaldol reaction has resulted
in the formation of the gluco-pyranoside (Fig. 1).
signed as methyl 5,7-O-benzylidene-3-deoxy-3-nitro-
a-D-glycero-
D-altro-septanoside 13. It is likely from the observed coupling con-
stants which were large for H-2 coupling to H-3, and H-5 coupling
to H-6, and the conformational restraints imparted by the benzyl-
idene ring, that the septanoside favours a chair conformation
rather than a twist-chair, boat or twist-boat conformation.13 Inter-
estingly, previous reports have detailed the nitroaldol reaction of
dialdehyde 1014 for the synthesis of 3-nitroseptanosides, but con-
trary to our results, product 13 did not feature as the major product
of the reaction. Comparing analytical data (mp and specific rota-
tion) obtained for 13 with those reported for minor products in
the literature reports14 provided further weight for our proposal
that the major product of our reaction was the 3-deoxy-3-nitro-
HO
HO
HO
HO
O
O
OBn
O2N
O2N
OH
OH
OMe
6
5
a-
D-glycero-
D-altro-septanoside 13.
The formation of 4-nitro-septanoside 14 illustrated that the
Figure 1.
nitroaldol reaction was also effective when the position of the dial-
dehyde within the sugar framework was altered, hence allowing
entry to 4-nitroseptanosides which can be considered as precur-
sors to 4-aminoseptanosides. Since 4-amino-glycosides, and their
analogues have received far less attention in the literature than
3-amino-glycosides and their analogues,15 this represents a useful
advance in synthetic methodology. The deduction of the stereo-
chemistry of 14 was again possible by using NMR spectroscopy.
However, the relative stereochemistry of the substituents at C-3,
4 and 5 could now no longer be confidently assigned on the basis
of the multiplicities observed, or the coupling constants, for H-2
(dd, J 3.5, 2.0 Hz), H-3 (m), H-4 (dd, J 9.5, 3.5) or H-5 (m). The
NOE spectrum proved more informative and showed that irradia-
tion of H-4 enhanced the signals of H-5 and 6 but not of the adja-
cent H-3. This would indicate that H-4, 5 and 6 are on the same
side of the ring and H-3 is on the opposite side of the ring, affording
These results are in agreement with previous literature reports
for pyranoside products, where the preferred trajectory of the nitr-
onate is that which will lead to the resulting nitro group being
equatorial to the ring, giving the most chair-like conformation
and minimising A(1,3) non-bonding interactions between the oxy-
gen atoms of the nitro group and the adjacent hydroxyl groups.9
As it did not prove possible in the above approach to bias the
reaction of unprotected glycosides, to form septanoside products,
our attention was next turned to using protected glycopyranosides
within the methodology. Diols 7, 8 and 9 were selected for study,
as these could allow access to 3-nitroseptanosides or 4-nitrosept-
anosides, extending the scope of the nitro aldol reaction that had
previously only been reported for the synthesis of 3-nitroseptano-
sides.7 In all cases the diols were formed by the literature meth-
ods10–12 and were then treated with sodium periodate (5 equiv)
at 0 °C for 5 h. Dialdehydes 10, 11 and 12 thus formed were used
without purification and were treated with the nitromethane an-
ion in 1 M NaOMe solution at low temperature and then allowed
to warm temperature overnight. Following neutralisation with
acetic acid, the mixtures were purified by flash column chromatog-
4-deoxy-4-nitro-a-D-glycero-L-manno-septanoside 14 as shown in
Figure 2. In light of these stereochemical assignments, the large
coupling constant of 9.5 Hz for H-4 can be assigned to the coupling
of H-4 with H-3, whilst the smaller coupling constant of 3.5 Hz re-
flects coupling between H-4 and H-5. With many resonances
appearing as multiplets, it is not possible to comment further from

2164
H. M. I. Osborn, A. Turkson / Tetrahedron: Asymmetry 20 (2009) 2162–2166
Table 1
Diol
Dialdehyde
Septanoside product
Yield over 2 steps (%)
OMe
OH
O
O
O
O
Ph
Ph
O
O
O
O
Ph
HO
O
43
O
O
OH
OMe
OMe
HO
NO2
7
10
13
OBn
BnO
OMe
OBn
O
O
O
O
HO
HO
OBn
HO
35
OBn
OBn
O
OMe
O2N
OH
OMe
8
14
11
OBn
BnO
BnO
O
OMe
O
OBn
O
O
BnO
HO
HO
OBn
HO
42
O
OMe
O2N
OH
OMe
9
15
12
7
BnO
H
OMe
H
O
The 1H NMR data for 15 were fully consistent with this stereo-
chemical assignment, with H-2 presented as a dd with J values of
6.5 (coupling to H-1) and 1.0 Hz (coupling to H-3). The H-3 and
H-5 presented as multiplets whilst H-4 was presented as a dd with
J values of 10 Hz (coupling to H-5) and 6.5 Hz (coupling to H-3). H-
6 coupled to H-5 with a J value of 10.0 Hz.
H
6
1
HO
NOE
H-4,6
2
5
4
3
H
OBn
H
H
NOE
H-4,5
O2N
OH
X
14
Figure 2.
3. Conclusions
Oxidative cleavage and nitroaldol protocols successfully al-
lowed the synthesis of nitro-pyranoside 6 in a good yield that
was comparable with those previously reported for related sub-
strates.9 Although unprotected glucopyranosides were not effec-
tive as precursors to 4-nitro-septanosides, the nitroaldol reaction
of regioselectively protected pyranosides 7, 8 and 9 did prove use-
ful for entry to either 3- or 4-nitroseptanosides 13, 14 and 15. Thus
targets 13, 14 and 15 were accessed in good yields of 43%, 35% and
42%, respectively. The NMR and NOE spectroscopic studies were
used to determine the stereochemical features of the targets. Since
a number of carbohydrate mimetics containing the amine func-
tional group have found interest as new antibacterial agents,17
the derivatives prepared herein are now being further modified
chemically, to afford 3-amino-pyranoside and 3-amino- and 4-
amino-septanosides. The results of these studies will be reported
in due course.
this study as to whether septanoside 14 prefers the chair-twist,
chair, boat or twist-boat conformation.
For entry to the final target 15, mannose-derived diol 9 was uti-
lised. A successful reaction was again seen here allowing entry to
4-nitro-septanoside 15 which was isomeric with 14. 4-Nitrosept-
anoside 15 was again characterised by 1H, 13C and NOE NMR spec-
troscopy in a similar manner to the previous derivatives 13 and 14.
NOE studies for 15 illustrated that irradiation of H-2 led to an
enhancement of the signals for H-3 and 4; irradiation of H-4 en-
hanced the signals of H-2 and 3. Furthermore, irradiation of H-4
showed no NOE enhancement of H-5. As the stereochemistry of
H-2 and H-1 are predefined from the mannopyranoside frame-
work, and for an enhancement of H-2 and 3 to be achieved by H-
4, product 15 would have to be 4-deoxy-4-nitro-
talo-septanoside, as illustrated in Figure 3.
a-D-glycero-D-
7
BnO
H
OMe
OBn
4. Experimental
O
H
6
1
H
2
5
Melting points were obtained using an Electrothermal digital
melting point apparatus. Specific rotation measurements were
measured using a Perkin–Elmer 341 polarimeter. Solutions were
made using CHCl3 or MeOH and measurements were taken at a
HO
O2N
4
3
H
OH
H
H
NOE
H-2,4
wavelength of 589 nm and are quoted in units of 10ꢀ1 deg cm2 gꢀ1
.
NOE
H-3,4
Infrared spectra were recorded on a Perkin–Elmer Paragon 1720-X
FT-IR spectrometer. Liquid samples were placed as thin films
between sodium chloride plates. Absorption maxima frequencies
15
Figure 3.

H. M. I. Osborn, A. Turkson / Tetrahedron: Asymmetry 20 (2009) 2162–2166
2165
are measured in wavenumbers (cmꢀ1). The following abbreviations
4.2. Methyl 5,7-O-benzylidene-3-deoxy-3-nitro-a-D-glycero-D-
are used to report the degree of absorption: s (strong), m (med-
ium), w (weak) and br (broad).
altro-septanoside 13
All 1H and 13C NMR spectra were recorded on a Bruker DPX-250
spectrometer or a Bruker AMX-400 spectrometer using CDCl3 or
CD3OD as an internal standard. 1H NMR spectra were recorded at
250 MHz or 400 MHz and chemical shifts (dH values) are quoted
in units of parts per million (ppm). The following abbreviations
are used: s (singlet), d (doublet), t (triplet), app. t (apparent triplet),
dd (double doublet), dt (double triplet), ddd (double double dou-
blet) and quin (quintet). Coupling constants (J values) are mea-
sured in hertz to the nearest 0.5 Hz. 13C NMR spectra were
recorded at 63 MHz or 101 MHz using CDCl3 as an internal stan-
dard and chemical shifts (dC values) are quoted in units of ppm.
High resolution mass spectrometric data were recorded on a
Hewlett Packard Series 1050 spectrometer for chemical ionisation
(CI) or electron impact ionisation (EI) or a Bruker MicroTof LC TOF
MS for electrospray ionisation (ESI). Molecular ions and molecular
ion fragments are reported as mass/charge (m/z) ratios.
Part A: Methyl 4,6-O-benzylidene-a-D
-glucopyranoside 710
(2.48 g, 8.79 mmol) was dissolved in methanol (50 mL) and cooled
to 0 °C. Next, NaIO4 (9.39 g, 44.00 mmol) was dissolved in distilled
water (150 mL) and added to the methanolic solution. The reaction
mixture was stirred for 5 h before evaporation of the solvent. The
white solid was partially dissolved with EtOAc and filtered through
a pad of silica and CeliteÒ. The organic phase was dried (MgSO4),
filtered and concentrated in vacuo to yield the crude dialdehyde
10 as a white solid (1.36 g).
Part B: In an oven-dried three-necked round-bottomed flask, so-
dium (2.40 g) was added portionwise to anhydrous methanol
(50 mL) under argon. Nitromethane (0.26 mL, 4.84 mmol) was
added to the sodium methoxide solution and the contents were
cooled to ꢀ40 °C. Crude dialdehyde 10 (1.36 g, 4.84 mmol) was sol-
ubilised in anhydrous acetonitrile (50 mL) and anhydrous DMF
(10 mL) and added dropwise to the methanolic solution. The con-
tents were cooled further to ꢀ64 °C and stirred under argon over-
night, after which it was allowed to warm to 9 °C. The reaction
mixture was re-cooled to ꢀ57 °C and then quenched with Amber-
liteÒ IR-120 (H+) and acetic acid. The solution was then filtered and
partitioned between water (60 mL) and CH2Cl2 (60 mL). The aque-
ous phase was further extracted with CH2Cl2 (2 ꢁ 60 mL). The or-
ganic phase was dried (MgSO4), filtered and concentrated in
vacuo. Flash column chromatography on silica gel (4:1 toluene/
EtOAc) yielded 13 as colourless crystals (1.29 g, 43%). Mp 189–
Flash chromatography was performed on silica gel 60 (Merck or
Fisher) using head pressure by means of compressed air or bellows.
TLC analysis was performed using Merck silica 60 F254 aluminium-
backed plates of 0.2 mm depth. Compounds were visualised on TLC
plates using UV light (k = 254 nm) or using an ethanol/sulfuric acid
dip (25:1), phosphomolybdic acid (20% ethanol), vanillin or ninhy-
drin spray.
All chemicals and solvents were obtained from Aldrich, Fisher
Scientific or Lancaster and used as required. Anhydrous solvents
were used as bought and glassware oven-dried prior to use. Exper-
imental procedures were carried out under an argon atmosphere
when an inert atmosphere was required.
190 °C; ½a 2D0
ꢂ
¼ þ23:7 (c 1.75, MeOH); mmax (NaCl disc/cmꢀ1) 3356
(br s, OH), 1598 (m, NO2 (asymmetric)), 1361 (s, NO2 (symmetric)),
1056 (m, C–O), 1033 (m, C–O), 1016 (m, C–O), 754 (m, CH (arom));
dH (400 MHz, CD3OD) 3.46 (3H, s, OCH3), 3.69 (1H, app. t, J 10.5,
C(7)H), 3.80 (1H, t, J 9.5, 3.0, C(5)H), 4.15 (1H, app. dt, J 10.0, 6.0,
C(6)H), 4.27 (1H, dd, J 10.5, 6.0, C(70)H), 4.50 (1H, br d, J 2.5,
C(4)H), 4.57 (1H, d, J 5.5, C(1)H), 4.62 (1H, dd, J 10.5, 5.5, C(2)H),
4.95 (1H, dd, J 10.5, 2.5, C(3)H), 5.62 (1H, s, PhCH), 7.36–7.38
(3H, m, Ph), 7.52–7.54 (2H, m, Ph); dC (101 MHz, CD3OD) 56.4
(OCH3), 59.0 (C6), 69.7 (C2), 70.2 (C7), 71.1 (C4), 81.5 (C5), 90.0
(C3), 102.2 (PhCH), 107.3 (C1), 127.5–129.9 (ArC), 139.1 (ArC); m/
z (CI) 342 ([M+H]+, 33%), 341 ([M]+, 39%), 310 (56), 169 (47), 149
(100). Found [M]+ 341.1119, C15H19NO8 requires 341.1111.
4.1. Benzyl 3-deoxy-3-nitro-b-D-glucopyranoside 5
Part A: Benzyl-b-
D
-glucopyranoside 116 (1.23 g, 4.55 mmol) was
dissolved in MeOH (20 mL) and cooled to 0 °C. Next, NaIO4 (4.88 g,
22.75 mmol) was dissolved in distilled water (20 mL) and added
dropwise to the methanol solution. The reaction mixture was stir-
red for 18 h before evaporation to dryness. The residue was diluted
with EtOAc and filtered through a pad of silica and CeliteÒ. The fil-
trate was concentrated in vacuo to yield crude dialdehyde 3
(630 mg).
4.3. Methyl 2-O-benzyl-4-deoxy-4-nitro-7-benzyloxymethyl-
a-
Part B: At first, 1 M NaOMe (1 mL) was added to a flask contain-
ing anhydrous CH2Cl2 (2 mL). Nitromethane (0.64 mL, 11.7 mmol)
was then added and the solution was cooled to ꢀ75 °C. The crude
dialdehyde 3 (630 mg, 2.35 mmol) in anhydrous CH2Cl2 (4 mL) was
added dropwise and the reaction mixture was stirred under argon
for 18 h, warming to 5 °C. The reaction mixture was evaporated to
dryness and passed through a DOWEX ion-exchange column elut-
ing with water. The combined aqueous fractions were extracted
with EtOAc (3 ꢁ 60 mL) and the organic phase was dried (MgSO4),
filtered and concentrated in vacuo. Flash column chromatography
on silica gel (1:1 toluene/EtOAc) yielded 5 as a colourless solid
D
-glycero- -manno-septanoside 14
L
Part A: Methyl 2,6-di-O-benzyl-a-D
-glucopyranoside 811
(496 mg, 1.33 mmol) was dissolved in methanol (20 mL) and
cooled to 0 °C. Next, NaIO4 (1.42 g, 6.63 mmol) was dissolved in
distilled water (20 mL) and added to the methanolic solution.
The reaction mixture was stirred for 5 h before evaporation of
the solvent. The white residue was diluted with EtOAc and filtered
through a pad of silica and CeliteÒ. The organic phase was dried
(MgSO4), filtered and concentrated in vacuo to yield the crude dial-
dehyde 11 as a colourless syrup (320 mg).
Part B: At first, 1 M NaOMe (1 mL) was added to a flask contain-
ing anhydrous CH2Cl2 (10 mL) and powdered 4 Å MS (242 mg),
after which the solution was cooled to ꢀ60 °C. Nitromethane
(0.23 mL, 4.29 mmol) was then added dropwise followed by dial-
dehyde (11) (320 mg, 0.859 mmol) in anhydrous CH2Cl2 (3 mL).
The reaction mixture was stirred under argon overnight, warming
to room temperature. The reaction was quenched by the dropwise
addition of 1 M HCl, before the contents were partitioned between
water (40 mL) and CH2Cl2 (40 mL). The aqueous phase was further
extracted with EtOAc (2 ꢁ 100 mL). The organic phase was dried
(MgSO4), filtered and concentrated in vacuo. Flash column chroma-
tography on silica gel (3:2 Et2O/petroleum ether (bp 30–40))
(422 mg, 31%). Mp 174–176 °C; ½a D20
¼ ꢀ29:1 (c 1.01, MeOH); mmax
ꢂ
(NaCl disc/cmꢀ1) 3424 (m, OH), 3247 (m, OH), 2915 (w, CH), 1553
(s, NO2 (antisymmetric)), 1369 (m, SO2 (symmetric)), 1082 (s, C–O),
1033 (s, C–O); dH (400 MHz, CD3OD) 3.40 (1H, ddd, J 12.0, 5.5, 2.5,
C(5)H), 3.78 (1H, dd, J 12.0, 5.5, C(6)H), 3.88 (1H, dd, J 10.5, 8.0,
C(2)H), 3.93 (1H, dd, J 12.0, 2.5, C(60)H), 4.02 (1H, app. t, J 10.0,
C(4)H), 4.49 (1H, d, J 8.0, C(1)H), 4.54 (1H, app. t, J 10.0, C(3)H),
4.73 (1H, d, J 12.0, OCH2Ph), 4.99 (1H, d, J 12.0, OCH2Ph); dC
(101 MHz, CD3OD) 62.1 (C6), 69.3 (C4), 71.9 (OCH2Ph), 72.4 (C2),
78.2 (C5), 96.0 (C3), 102.8 (C1), 128.8–129.3 (ArC), 138.8 (ArC);
m/z (CI) 300 ([M+H]+, 2%), 282 (26), 181 (100). Found [M+H]+
300.1093, C13H18NO7 requires 300.1083.

2166
H. M. I. Osborn, A. Turkson / Tetrahedron: Asymmetry 20 (2009) 2162–2166
yielded 14 as a colourless syrup (202 mg, 35%). ½a D20
ꢂ
¼ þ96:9 (c 1.0,
67.9 (C5), 69.0 (C6), 70.6 (C7), 72.9 (OCH2Ph), 73.3 (C3), 73.7
(OCH2Ph), 80.7 (C2), 93.9 (C4), 102.9 (C1), 127.8–128.7 (ArC),
137.2–137.4 (ArC); m/z (ESI) 456 ([M+Na]+, 100%). Found
[M+Na]+ 456.1623, C22H27NO8Na requires 456.1629.
CHCl3); mmax (NaCl disc/cmꢀ1) 3460 (br s, OH), 2913 (s, CH), 1557
(s, NO2 (antisymmetric)), 1497 (m C@C (arom)), 1454 (s, C@C
(arom)), 1366 (s, NO2 (symmetric)), 1096 (s, C–O), 1045 (s, C–O),
739 (s, CH (arom)), 698 (s, CH, arom)); dH (400 MHz, CDCl3) 2.94
(1H, br s, C(3)OH), 3.12 (1H, br s, C(5)OH), 3.45 (3H, s, OCH3),
3.59 (1H, d, J 1.5, C(7)H), 3.60 (1H, d, J 1.0, C(70)H), 4.11 (1H, dd, J
3.5, 2.0, C(2)H), 4.43–4.44 (2H, m, C(5,6)H), 4.49–4.58 (3H, m,
C(3)H, OCH2Ph), 4.64 (1H, d, J 11.5, OCH2Ph), 4.73 (1H, d, J 3.5,
C(1)H), 4.88 (1H, d, J 11.5, OCH2Ph), 4.97 (1H, dd, J 9.5, 3.5,
C(4)H), 7.24–7.36 (10H, m, Ph); dC (101 MHz, CDCl3) 56.0 (OCH3),
66.9 (C3), 69.2 (C5 or C6), 70.3 (C7), 70.5 (C5 or C6), 73.4 (OCH2Ph),
75.7 (OCH2Ph), 81.4 (C2), 91.7 (C4), 100.2 (C1), 127.7–128.6 (ArC),
137.3–137.9 (ArC); m/z (CI) 434 ([M+H]+, 3%), 361 (30), 342 (14),
310 (41), 181 (100). Found [M+H]+ 434.1804, C22H28NO8 requires
434.1815.
Acknowledgements
We thank the EPSRC and the Department of Chemistry for the
provision of a PhD studentship to A.T. We are also grateful to Mr.
Peter Heath for his help with the NMR studies discussed in this
paper.
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Part A: Methyl 2,6-di-O-benzyl-a-D
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colour syrup (153 mg, 42%). ½a D20
¼ þ49:4 (c 1.06, CHCl3); mmax
ꢂ
(NaCl disc/cmꢀ1) 3437 (m, OH), 2918 (m, CH), 1555 (s, NO2 (anti-
symmetric)), 1453 (m, C@C (arom)), 1368 (m, NO2 (symmetric)),
1102 (s, C–O), 1060 (s, C–O), 739 (m, CH (arom)), 698 (m, CH
(arom)); dH (400 MHz, CDCl3) 3.42 (3H, s, OCH3), 3.54 (1H, dd, J
6.5, 1.0, C(2)H), 3.69 (1H, dd, J 10.0, 3.5, C(7)H), 3.76 (1H, dd, J
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m, C(3)H), 4.61–4.67 (4H, m, C(5)H, OCH2Ph), 4.74 (1H, d, J 6.5,
C(1)H), 7.29–7.38 (10H, m, Ph); dC (101 MHz, CDCl3) 56.2 (OCH3),
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