De Novo Asymmetric Synthesis of a 6-O-Methyl-d-glycero-l-gluco-heptopyranose-Derived Thioglycoside for the Preparation of Campylobacter jejuni NCTC11168 Capsular Polysaccharide Fragments

Article abstract of DOI:10.1021/acs.joc.6b00296

An enantioselective de novo synthesis of a thioglycoside derivative of the 6-O-methyl-d-glycero-l-gluco-heptopyranose residue found in the Campylobacter jejuni NCTC11168 (HS:2) capsular polysaccharide is reported. The compound is obtained from a furfural-derived chiral diol in 11 steps. Notably, compared to the only previous synthesis of this molecule, this approach significantly reduces the number of purification steps required to obtain the target.

Full text of DOI:10.1021/acs.joc.6b00296

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Note
De novo asymmetric synthesis of a 6-O-methyl-D-glycero-L-
gluco-heptopyranose-derived thioglycoside for the preparation of
Campylobacter jejuni NCTC11168 capsular polysaccharide fragments
Roger A. Ashmus, Anushka B. Jayasuriya, Ying-Jie Lim, George A. O'Doherty, and Todd L. Lowary
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00296 • Publication Date (Web): 16 Mar 2016
Downloaded from http://pubs.acs.org on March 19, 2016
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De novo asymmetric synthesis of a 6ꢀOꢀmethylꢀDꢀglyceroꢀLꢀ
6
7
8
9
glucoꢀheptopyranoseꢀderived thioglycoside for the
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preparation of Campylobacter jejuni NCTC11168 capsular
polysaccharide fragments
Roger A. Ashmus,† Anushka B. Jayasuriya,† YingꢀJie Lim,†
George A. O’Doherty‡ and Todd L. Lowary*,†
†Alberta Glycomics Centre and Department of Chemistry, The University of Alberta, Edmonton,
Alberta T6G 2G2, Canada
‡ Department of Chemistry, Northeastern University, 360 Huntington Ave, Boston, MA 02115
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Graphical Abstract:
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Abstract:
An enantioselective de novo synthesis of a thioglycoside derivative of the 6ꢀOꢀmethylꢀ
ꢀglucoꢀheptopyranose residue found in the Campylobacter jejuni NCTC11168 (HS:2) capsular
D
ꢀglyceroꢀ
L
polysaccharide is reported. The compound is obtained from a furfuralꢀderived chiral diol in 11
steps. Notably, compared to the only previous synthesis of this molecule, this approach
significantly reduces the number of purification steps required to obtain the target.
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A common cause of bacterial gastroenteritis worldwide is infection by the Gramꢀnegative
bacterium Campylobacter jejuni.1 The symptoms associated with a C. jejuni infection range from
mild to severe diarrhea, and in some cases the disease can lead to a lifeꢀthreatening neurological
disorder, Guillain–Barré syndrome.2,3 All campylobacter species produce a speciesꢀspecific
capsular polysaccharide (CPS) that plays key roles in the interaction between the organism, host,
and environment. For instance, C. jejuni CPSs have been demonstrated to be important for
bacterial virulence, serum resistance, and colonization.4,5 Vaccines generated from C. jejuni CPSs
are in clinical trials6,7 and interfering with the biochemical pathways that produce these glycans
may lead to novel approaches for treating these infections.
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In ongoing efforts toward understanding campylobacter CPS biosynthesis,8,9 we have
focused our attention on C. jejuni NCTC11168 (HS:2). This organism produces a CPS with a
tetrasaccharide repeating unit containing a number of unusual motifs (Figure 1).10,11 These
include phaseꢀvariable modifications (e.g., methyl phosphoramidates, aminoglycerol amides, Oꢀ
methylations) and rare monosaccharides, in particular, an Nꢀacetylꢀgalactosamine residue in the
furanose ring form and a 6ꢀOꢀmethylꢀheptose residue with the
D
ꢀglyceroꢀ
L
ꢀgluco
stereochemistry.
HO O
HO
HO OH
NHAc
O
O
HO
NH
O
H2N
H3CO
O
O
O
O
O
P
O
OH
HO
HO
O
OH
HO
H3CO
Figure 1. Repeating unit of CPS from C. jejuni 11168(HS:2)
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Probing the biosynthetic enzymes involved in the assembly of this glycan requires the
synthesis of fragments of this structure and in turn access to these unusual carbohydrate
derivatives. In a previous publication, we described the synthesis of two derivatives of the
heptose residue that could be used as donors in glycosylation reactions: thioglycoside 1 and
trichloroacetimidate 2 (Figure 2).12 The two key steps in that route involved a diastereoselective
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divinylzinc addition to aldehyde 3 (obtained from
subsequent modifications led to 1 and 2. The preparation of 1 and 2 were achieved in 16 and 18
steps, respectively, from ꢀgalactose. Although this approach could be used to prepare gram
Dꢀgalactose) followed by ozonolysis of 4;
D
quantities of these compounds, the number of chromatographic purification steps led us to
consider other more efficient approaches.
BnO
CH3O BnO
BnO
OH
OH
(CH2 CH)2Zn
THF
O
H3CO
BnO
OH OBn
OBn
3
4
O3, CH2Cl2-CH3OH
OH
X
BnO
BnO
H CO
BnO
O
O
OH
BnO
OBn
BnO
H CO
BnO
3
3
1 X = STol
2 X = OC(=NH)CCl3
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Figure 2. Key steps in a previous route to
and 2.12
D
ꢀglyceroꢀ
L
ꢀglucoꢀheptoseꢀbased glycosyl donors 1
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Previous reports from the Ogasawara and O’Doherty groups have described the synthesis
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of Dꢀ and L
ꢀhexopyranoses from furfural through pathways involving either diol 6 and enone 7,13
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8
9
or pyranone 8 (Figure 3A).14ꢀ17 We envisioned that 1 (and in turn 2) could be synthesized via a
combination of these approaches (Figure 3B). Heptose 1 could be obtained from pyranone 9
through selective reduction and oxidation chemistry. Pyranone 9, already seven carbons in length,
could be produced from the benzyl protected diol 618 after a regioselective methylation, an
Achmatowicz reaction, and a selective pivaloylation. We describe here the successful
implementation of this approach (Scheme 1).
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O
HO
O
A
OR
O
OH
RO
O
Ogasawara
O
R = TBS, Bn, or Nap
R = TBS, Bn, or Nap
6
7
O
O
OR
O
OR
HO
HO
TBSO
O'Doherty
OH
HO
O
HO
R = Bz, Piv, or Boc
D- or L-
hexopyranosides
8
B
CH3O
H
OBn
OH
BnO
O
OPiv
O
1
O
6
9
Figure 3. A. Previous syntheses of hexopyranoses from furfural. B. Retrosynthesis analysis of 1.
After synthesizing the benzylꢀprotected diol 6,13,18 which can be easily obtained on a
multiꢀgram scale in four steps and a 48% overall yield from furfural, various conditions for
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regioselective methylation were explored (Table 1). The 2ꢀaminoethyl diphenylborinic acid
catalyzed alkylation, described by Taylor and coworkers, proved to be the optimal method
although no regioselectivity was observed (Scheme 1).19,20 This approach showed complete
(TLC) conversion of 6 into 10a and 10b, albeit in an approximately 1:1 inseparable mixture as
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1
determined by H NMR spectroscopy. Subsequent Achmatowicz reaction of 10a and 10b using
NBS as the oxidant in the presence of NaOAc and NaHCO3, followed by an αꢀselective
pivaloylation afforded pure pyranone 9 in 38% yield over three steps (average yield of 72% per
step) from 6. The structure of pyranone 9 is supported by J1,2 coupling constant value of 3.7 Hz,
which closely matches the 1,2ꢀallylic coupling constants in similar pyranones.16,21
Table 1. Conditions explored for the regioselective methylation of 6.
HO
HO
H3CO
H3CO
OBn
OBn
OBn
OBn
OCH3
O
O
O
O
+
+
OH
OCH3
10a
OH
10b
10c
6
Product
10a:10b:10c
entry
conditions
yield
0%
i) nBu2SnO, toluene, reflux
ii) CH3I (1.5 equiv), 40 °C
i) nBu2SnO, toluene, reflux
ii) CH3OTf (1.2 equiv)
i) nBu2SnO, toluene, reflux
ii) CH3OTf (1.2 equiv), 0 °C
1
2
3
4
5
6
ꢀꢀꢀꢀꢀ
0:1:0a
~1:4:0a
~2:3:0a
~0:0:1e
~1:1:0a
~10%b,c
55%b
~22%d
n.d.
CH3I (8 equiv), AgO,
CH3CN, reflux
CH3I (1.5 equiv), NaH, THF
CH3I (3 equiv), K2CO3,
borinate,f CH3CN, 60 °C
95%b
a product ratio determined by 1H NMR spectroscopy. b isolated yield. c unknown impurity
present. d yield based on 1H NMR spectroscopy. e TLC analysis showed dimethylation to be the
favored adduct with little to no monomethylation product. f borinate = 2ꢀaminoethyl
diphenylborinate.
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a
Scheme 1. Synthetic scheme for the asymmetric de novo synthesis of 1. Yield based on
recovered starting material and product lacking a Piv group.
The stereoselective reduction of pyranone 9 was then explored (Table 2). Despite
precedence for the stereoselective reduction of similar substrates that lack an additional
substituent at Cꢀ6,14,16,17,21ꢀ23 the reduction of 9 suffered from modest stereoselectivity albeit in
favor of the desired diastereomer 11a. Although complete stereoselective reduction was achieved
using
L
ꢀselectride, substantial amounts of the 1,4ꢀconjugate addition product were also observed.
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9
It was subsequently discovered that the best results were obtained by Luche reduction of 9 at −78
°C. Under these conditions, an approximately 2:1 inseparable mixture of diastereomeric alcohols
11a/11b, in which the desired isomer 11a predominated, was formed.
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Table 2. Conditions explored for the stereoselective reduction of 9.
OPiv
OPiv
OPiv
O
O
O
BnO
H3CO
HO
BnO
HO
BnO
+
O
H3CO
H3CO
11b
11a
9
productd
11a:11b
entry
conditions (equiv.)
solvent
temp
yield
86%a
NaBH4 (1)
CeCl3·7H2O (0.5)
NaBH4 (1)
1:1 CH2Cl2–
CH3OH
1:1 CH2Cl2–
CH3OH
1:1 CH2Cl2–
CH3OH
1:1 CH2Cl2–
CH3OH
1
2
3
4
5
6
0 °C
~1:2
~1:1
~2:1
~7:2
1:0
–30 °C
–78 °C
–78 °C
–78 °C
–78 °C
90%a
CeCl3·7H2O (0.5)
NaBH4 (1)
CeCl3·7H2O (0.5)
NaBH4 (1)
89%a
~55%a,b,c
~40%a,b,c
CeCl3·7H2O (0.2)
LꢀSelectride (1)
THF
NaBH4 (1)
THF
~4:1
~35%a,b,c
a
b
c
d
isolated yield. 1,4ꢀconjugate addition observed. impurity of unknown structure present.
product ratio determined by 1H NMR spectroscopy.
Benzylation of this mixture of 11a/11b provided 12a/12b. Although purification of the
diastereomers can be achieved at this step, we instead carried the mixture forward.
Dihydroxylation proceeded selectively from the face opposite that of the pivalate ester to afford
13 in 42% yield over three steps from 9 (average yield of 75% per step). Importantly, only
diastereomer 12a underwent dihydroxylation, presumably due to the pseudoaxial orientation of
the groups at Cꢀ1 and Cꢀ4 in 12b. This fortuitous chemoselectivity significantly eased
purification of the desired product. Tinꢀcatalyzed alkylation of diol 13 afforded the desired 3,4,7ꢀ
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triꢀOꢀbenzylated adduct 14 in 84% yield. The J3,4 and J4,5 coupling constant values of 9.5 and 9.5
Hz supports the correct configuration of Cꢀ2, Cꢀ3, and Cꢀ4 stereocenters in alcohol 14.
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Subsequent stereoinversion of Cꢀ2 alcohol was achieved by triflation followed by
treatment with sodium nitrite in DMF at 60 °C. These conditions produced a 73% yield of an
approximately 2:5 mixture of 15a and 15b, which was formed through migration of the pivalate
ester from Oꢀ1 to Oꢀ2. The respective J1,2 coupling constant values of 3.6, 3.7, and 8.3 Hz of
alcohols 15a, 15bα, and 15aβ supports the stereoinversion at Cꢀ2. Other conditions (Table 3)
were explored to either prevent or further promote the migration of the pivalate group, but these
conditions also afforded a mixture of regioisomers. Alternative stereoinversion approaches, such
as a Mitsunobu reaction or oxidation to the ketone and subsequent reduction either did not
produce the desired compound, or were poorly selective. Regioisomers 15a and 15b were then
treated with pꢀtolyl disulfide and trimethylphosphine to afford 16 (15a remained unreactive) in
90% yield, based on the amount of 15b in the mixture. Thioglycoside 16 was then treated with
excess NaH in the presence of benzyl bromide at 60 °C. Under these conditions, we could
conveniently both remove the pivalate ester and protect the resulting alcohol as a benzyl ether
leading, in 95% yield, to the heptose thioglycoside 1. The data for 1 matched that previously
reported.12 The minor adduct formed in the inversion step, 15a, could also be converted to 1
following the original protocol published after acetylation of the alcohol.12
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Table 3. Conditions explored to invert Cꢀ2 stereochemistry in 14.
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9
OPiv
OPiv
OH
OH
BnO
BnO
BnO
BnO
H3CO
BnO
BnO
O
O
O
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+
OPiv
H3CO
H3CO
BnO
15b
BnO
15a
BnO
14
OH
product
obtained
~3:2b
entry
conditions
1) Swern oxidation
2) NaBH4, CH2Cl2–CH3OH, –78 °C
1) Tf2O, pyridine, CH2Cl2, –10 to 10 °C
2) NaNO2, DMF, 60 °C
yield
88%a
73%a
79%a
1
2
3
15a–14
~2:5b
15a–15b
~4:1b
15a–15b
1) Tf2O, pyridine, CH2Cl2, –10 to 10 °C
2) H2O, DMF
a isolated yield. b product ratio determined by 1H NMR spectroscopy.
In summary, we describe the de novo asymmetric synthesis of the
D
ꢀglyceroꢀ
L
ꢀglucoꢀ
heptoseꢀderived thioglycoside 1. This route provides the target molecule, which is a useful donor
in the synthesis of C. jejuni HS:2 CPS glycoconjugates, more efficiently than the only other
previously reported synthesis of this compound or any other
DꢀglyceroꢀLꢀglucoꢀheptose
derivative.12 Thioglycoside 1 was produced in 11 steps from the easily prepared benzyl protected
diol 6 (15 steps from furfural), compared to 16 steps from
Dꢀgalactose. Importantly, the route
described here significantly reduced the number of purification steps required. From 6, only six
purification steps (via flash chromatography) were used, compared to 15 steps required by our
previously reported route starting from
Dꢀgalactose. The reduction in the number of required
purifications, significantly facilitates the largeꢀscale synthesis of 1. Efforts are currently
underway to use 1, and the related trichloroacetimidate 2, in the preparation of glycoconjugates
containing this monosaccharide.
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Experimental Section
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General Experimental Methods. All reagents were purchased from commercial sources
and were used without further purification unless noted. Solvents used in reactions were purified
by successive passage through columns of alumina and copper under argon. Unless stated
otherwise, all reactions were carried out at room temperature and monitored by TLC on Silica
Gel Gꢀ25 F254 (0.25 mm). TLC spots were detected under UV light and/or by charring with a
solution of pꢀanisaldehyde in ethanol, acetic acid and H2SO4. Column chromatography was
performed on Silica Gel 60 (40–60 ꢁm). In some cases, a dry loading technique (substrate
adhered to silica, solvent removed, then loaded on column) was used for purification. Solvents
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1
were evaporated under reduced pressure on a rotary evaporator. H NMR spectra were recorded
using 400, 500, or 600 MHz NMR instruments and were referenced to residual proton signal of
CDCl3 (7.26 ppm). 13C NMR spectra were recorded using 126 MHz (cold probe) NMR
1
instrument and were referenced to residual 13C signals of CDCl3 (77 ppm). H NMR data are
reported as though they were first order, and peak assignments were made on the basis of 2Dꢀ
NMR (1H –1H COSY and HSQC) experiments. ESIꢀMS spectra (timeꢀofꢀflight analyzer) were
recorded on samples dissolved in THF or CH3OH and added NaCl. Optical rotations were
measured at 22 ± 2 °C at the sodium D line (589 nm) and are in a microcell (10 cm, 1 mL) in
units of deg·mL(dm·g)ꢀ1.
(R)ꢀ2ꢀ(benzyloxy)ꢀ1ꢀ((2S,6S)ꢀ3ꢀoxoꢀ6ꢀ(pivaloyloxy)ꢀ3,6ꢀdihydroꢀ2Hꢀpyranꢀ2ꢀyl)ethyl
pivalate (9). To benzyl protected diol 6 (1 g, 4.03 mmol) under argon were sequentially added 2ꢀ
aminoethyl diphenylborinate (181 mg, 0.806 mmol), K2CO3 (613 mg, 4.43 mmol), anhydrous
CH3CN (40 mL), and CH3I (5.55 mL, 12.09 mmol). The reaction mixture was heated to 60 °C
and stirred for 16 h. The mixture was poured over a solution of brine (20 mL) and H2O (20 mL),
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then extracted with EtOAc (3 × 40 mL). The organic layers were combined, dried over Na2SO4,
filtered, and concentrated. To the resulting residue were sequentially added NaHCO3 (677 mg,
8.06 mmol), NaOAc·3H2O (548 mg, 4.03 mmol), and a 4:1 THF–H2O solution (40 mL). The
mixture was cooled to 0 °C and NBS (932 mg, 5.24 mmol) was added in portions over ~20 min.
For optimal results either newly purchased or freshly recrystallized (from H2O) NBS should be
used. After complete addition of the NBS, the reaction mixture was stirred at 0 °C for 1.5 h. The
excess NBS was quenched by addition of a saturated aqueous Na2S2O3 solution (20 mL), stirred
for ~20 min, poured over a saturated aqueous NaHCO3 solution (20 mL), and then extracted with
EtOAc (3 × 40 mL). The organic layers were combined and then washed with a minimal amount
of brine. The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was
dried under vacuum in the presence of P2O5 for ~2 h. To the residue under argon were added
anhydrous CH2Cl2 (20 mL), Et3N (1.69 mL, 12.09 mmol) and DMAP (25 mg, 0.20 mmol). The
mixture was cooled to –78 °C, then PivCl (744 ꢁL, 6.05 mmol) was added dropwise over ~3 min.
The reaction mixture was stirred at –78 °C for 1.5 h. The reaction mixture was poured over a
saturated aqueous NH4Cl solution (30 mL) and extracted with CH2Cl2 (100 mL). The organic
layer was dried over Na2SO4, filtered and concentrated. The residue was purified by flash
chromatography in 4:1→3:1 hexanes–EtOAc to afford 9 (555 mg, 38%) as a pale yellow oil. Rf
0.37 (3:1 hexanes–EtOAc); [α]D +55.4 (1.0 c, CHCl3); 1H NMR (500 MHz; CDCl3): δ 7.38–7.29
(m, 5H, Ar), 6.95 (dd, 1H, J = 10.3, 3.7 Hz, Hꢀ2), 6.63 (d, 1H, J = 3.7 Hz, Hꢀ1), 6.30 (d, 1H, J =
10.3 Hz, Hꢀ3), 4.71 (d, 1H, J = 1.8 Hz, Hꢀ5), 4.57 (d, 1H, J = 12.4 Hz, PhCH2O) 4.55 (d, 1H, J =
12.3 Hz, PhCH2O), 4.19 (ddd, 1H, J = 8.0, 5.9, 2.0 Hz, Hꢀ6), 3.71 (dd, 1H, J = 9.4, 5.7 Hz, Hꢀ7a),
3.66 (dd, 1H, J = 9.4, 8.2 Hz, Hꢀ7b), 3.43 (s, 3H, OCH3), 1.20 (s, 9H, C(CH3)3); 13C NMR (126
MHz; CDCl3): δ 194.1 (C4=O), 176.7 (C=O), 142.2 (C2), 138.0 (Ar), 129.2 (C3), 128.4 (Ar),
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127.6 (Ar), 127.4 (Ar), 87.0 (Cꢀ1), 77.8 (Cꢀ6), 75.8 (Cꢀ5), 73.4 (PhCH2O), 67.3 (Cꢀ7), 59.8
(OCH3), 39.2 (C(CH3)3, 27.0 (C(CH3)3; HRMS (ESI) Calc. for (M + Na) C20H26NaO6: 385.1622.
Found 385.1620. *Note: When scale was increased to 30 mmol, the yield decreased to 26% over
3 steps.
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4,7ꢀDiꢀOꢀbenzylꢀ6ꢀOꢀmethylꢀ1ꢀOꢀpivolylꢀ
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ꢀglyceroꢀαꢀ ꢀmannoꢀheptopyranose (13).
L
To pyranone 9 (1.3 g, 3.59 mmol) was added an anhydrous 1:1 CH2Cl2–CH3OH solution (18
mL); CeCl3·7H2O (670 mg, 1.80 mmol) was then added. The mixture was stirred, with sonication
if necessary, until a homogenous solution was achieved. The mixture was cooled to –78 °C and
then NaBH4 (136 mg, 3.59 mmol) was added in five portions over ~5 min. The reaction mixture
was stirred at –78 °C for 30 min before being diluted with Et2O (10 mL). A saturated aqueous
NaHCO3 solution (10 mL) was added and the mixture was then extracted with Et2O (3 × 40 mL).
The organic layers were combined, washed with brine, dried over Na2SO4, filtered, and
concentrated. The residue was dried under vacuum in the presence of P2O5 for ~3 h. To the
residue under argon was added anhydrous DMF (26 mL) and BnBr (1.12 mL, 7.18 mmol). The
mixture was stirred and NaH (215 mg, 5.39 mmol) was added in three portions over 0.5 h before
being stirred for an additional 1.5 h. Excess NaH was quenched by addition of HOAc (150 ꢁL).
The mixture was concentrated and the resulting residue was diluted with EtOAc (100 mL) and
washed with a solution of brine (15 mL) and then H2O (15 mL). The organic layer was then
concentrated. To the residue were sequentially added a 5:1 acetone–H2O solution (30 mL), NMO
(630 mg, 5.39 mmol), and a 5% OsO4 in tBuOH (600 ꢁL, ~3 mol%). The reaction mixture was
stirred for 30 h and the mixture was poured over a solution of saturated aqueous Na2S2O3 solution
diluted with equal volume of H2O (60 mL), then extracted with EtOAc (3 × 50 mL). The organic
layers were combined, dried over Na2SO4, filtered, and concentrated. The resulting residue was
purified by flash chromatography in 1:1→2:1 EtOAc–hexanes to afford diol 13 (739 mg, 42%) as
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a clear oil. Rf 0.43 (2:1 EtOAc–hexanes); [α]D –26.6 (1.0 c, CHCl3); H NMR (498 MHz;
CDCl3): δ 7.43–7.29 (m, 10H, Ar), 6.12 (d, 1H, J = 1.7 Hz, Hꢀ1), 4.90 (d, 1H, J = 11.3 Hz,
PhCH2O), 4.75 (d, 1H, J = 11.3 Hz, PhCH2O), 4.53 (s, 2H, PhCH2O), 3.97–3.89 (m, 3H, Hꢀ2, Hꢀ
3, Hꢀ4), 3.83 (ddd, 1H, J = 6.0, 6.0, 1.7, Hꢀ6), 3.81 (dd, 1H, J = 9.2, 1.3 Hz, Hꢀ5), 3.75 (dd, 1H, J
= 9.7, 6.0 Hz, Hꢀ7), 3.60 (dd, 1H, J = 9.7, 6.1 Hz, Hꢀ7b), 3.49 (s, 3H, OCH3), 2.98 (br s, 1H, C2ꢀ
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OH), 2.63 (d, 1H, J = 6.2 Hz, C3ꢀOH), 1.16 (s, 9H, C(CH3)3); C NMR (126 MHz; CDCl3): δ
176.1 (C=O), 138.2 (Ar), 138.1 (Ar), 128.7 (Ar), 128.4 (Ar), 128.1 (2C, Ar, Ar), 127.6 (Ar),
127.5 (Ar), 93.0 (Cꢀ1), 76.5 (Cꢀ6), 75.0 (PhCH2O), 74.9 (Cꢀ3/Cꢀ4), 73.4 (PhCH2O), 72.9 (Cꢀ5),
72.2 (Cꢀ3/Cꢀ4), 70.1 (Cꢀ2), 69.3 (Cꢀ7), 58.6 (OCH3), 39.0 (C(CH3)3), 27.0 (C(CH3)3; HRMS
(ESI) Calc. for (M + Na) C27H36NaO8: 511.2302. Found 511.2299.
3,4,7ꢀTriꢀOꢀbenzylꢀ6ꢀOꢀmethylꢀ1ꢀOꢀpivolylꢀ
D
ꢀglyceroꢀαꢀ ꢀmannoꢀheptopyranose (14).
L
To diol 13 (1.5 g, 3.07 mmol) in anhydrous toluene (30 mL), nBu2SnO (841 mg, 3.38 mmol) was
added. A Dean–Stark apparatus was attached, filled w/ toluene, and the mixture was heated to
reflux for 8 h. The mixture was cooled to room temperature, the Dean–Stark apparatus was
removed and then nBu4NI (1.25 g, 3.38 mmol) and BnBr (450 ꢁL, 3.79 mmol) were added. The
reaction mixture was heated to 100 °C and stirred for 17 h, before being cooled and then poured
over a solution of saturated aqueous Na2S2O4 solution (30 mL) and H2O (30 mL) and then
extracted with EtOAc (120 mL). The organic layer was washed with brine (20 mL), dried over
Na2SO4, filtered, and concentrated. The residue was then purified by flash chromatography in
3:2→1:1 hexanes–EtOAc to afford 14 (1.5 g, 84%) as clear viscous oil. Rf 0.50 (1:1 hexanes–
EtOAc); [α]D –41.3 (1.0 c, CHCl3); 1H NMR (498 MHz; CDCl3): δ 7.39–7.28 (m, 15H, Ar), 6.14
(d, 1H, J = 1.8 Hz, Hꢀ1), 4.98 (d, 1H, J = 10.9 Hz, PhCH2O), 4.75 (d, 1H, J = 11.8 Hz, PhCH2O),
4.73 (d, 1H, J = 11.7 Hz, PhCH2O), 4.69 (d, 1H, J = 10.9 Hz, PhCH2O), 4.52 (app. s, 2H,
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PhCH2O), 4.12 (dd, 1H, J = 9.5, 9.5 Hz, Hꢀ4), 3.90–3.80 (m, 4H, Hꢀ2, Hꢀ3, Hꢀ5, Hꢀ6), 3.75 (dd,
1H, J = 9.7, 6.0 Hz, Hꢀ7a), 3.59 (dd, 1H, J = 9.7, 6.1 Hz, Hꢀ7b), 3.47 (s, 3H, OCH3), 2.56 (d, 1H,
J = 2.6 Hz, C2ꢀOH), 1.13 (s, 9H, C(CH3)3); 13C NMR (126 MHz; CDCl3): δ 175.9 (C=O), 138.3
(Ar), 138.2 (Ar), 137.5 (Ar), 128.6 (Ar), 128.5 (Ar), 128.3 (Ar), 128.2 (Ar), 128.1 (Ar), 128.0
(Ar), 127.9 (Ar), 127.5 (2C, Ar, Ar), 92.8 (Cꢀ1), 79.7 (Cꢀ2/Cꢀ3/Cꢀ4/Cꢀ5), 76.3 (Cꢀ2/Cꢀ3/Cꢀ4/Cꢀ
5), 75.4 (PhCH2O), 73.4 (PhCH2O), 73.2 (Cꢀ2/Cꢀ3/Cꢀ4/Cꢀ5), 73.1 (Cꢀ2/Cꢀ3/Cꢀ4/Cꢀ5), 72.1
(PhCH2O), 69.3 (Cꢀ7), 67.7 (Cꢀ2), 58.6 (OCH3), 39.0 (C(CH3)3), 27.0 (C(CH3)3; HRMS (ESI)
Calc. for (M + Na) C34H42NaO8: 601.2772. Found 601.2768.
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3,4,7ꢀTriꢀOꢀbenzylꢀ6ꢀOꢀmethylꢀ1ꢀOꢀpivolylꢀ
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ꢀglyceroꢀαꢀ
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ꢀglucoꢀheptopyranose (15a)
and 3,4,7ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀmethylꢀ2ꢀOꢀpivolylꢀ ꢀglyceroꢀα/βꢀ
D
L
ꢀglucoꢀheptopyranose (15b).
To 14 (1.5 g, 2.59 mmol) in anhydrous CH2Cl2 (26 mL) under argon was added anhydrous
pyridine (1.9 mL, 23.31 mmol). The mixture was cooled to –10 °C and Tf2O (1.3 mL, 7.77
mmol) was added dropwise via syringe over ~7 min. The reaction mixture was gradually warmed
to 10 °C over 2.5 h. After which, the reaction mixture was poured over an ice cold 1M HCl
solution (25 mL) and extracted with CH2Cl2 (75 mL). The organic layer was then sequentially
washed with ice cold H2O (25 mL), a saturated aqueous NaHCO3 solution (25 mL), and brine (25
mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The residue was dried
under vacuum in the presence of P2O5 for 1 h. To the residue under argon was added anhydrous
DMF (18 mL) and NaNO2 (894 mg, 12.95 mmol). The reaction mixture was heated to 60 °C for
10 h. The mixture was concentrated, diluted with EtOAc (120 mL), and then washed with brine
(25 mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The resulting
residue was purified by flash chromatography in 3:1→2:1 hexanes–EtOAc to afford isomers 15a
(320 mg, 21%) and 15b (780 mg, 52%). Data for 15a: Pale yellow oil. Rf 0.45 (2:1 hexanes–
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EtOAc); [α]D –50.4 (1.0 c, CHCl3); 1H NMR (498 MHz; CDCl3): δ 7.41–7.29 (m, 15H, Ar), 6.20
(d, 1H, J = 3.6 Hz, Hꢀ1), 4.98 (d, 1H, J = 10.9 Hz, PhCH2O), 4.95 (d, 1H, J = 11.3 Hz, PhCH2O),
4.87 (d, 1H, J = 11.3 Hz, PhCH2O), 4.70 (d, 1H, J = 10.9 Hz, PhCH2O), 4.53 (s, 2H, PhCH2O),
3.90–3.79 (m, 5H, Hꢀ2, Hꢀ3, Hꢀ4, Hꢀ5, Hꢀ6), 3.73 (dd, 1H, J = 9.7, 5.9 Hz, Hꢀ7a), 3.58 (dd, 1H, J
= 9.7, 6.2 Hz, Hꢀ7b), 3.48 (d, 3H, J = 1.7 Hz, OCH3), 1.88 (s, 1H, OH), 1.19 (s, 9H, C(CH3)3);
13C NMR (126 MHz; CDCl3): δ 176.7 (C=O), 138.3 (Ar), 138.0 (2C, Ar, Ar), 128.6 (2C, Ar, Ar),
128.4 (Ar), 128.1 (Ar), 128.0 (3C, Ar, Ar, Ar), 127.6 (Ar), 127.5 (Ar), 91.6 (Cꢀ1), 82.5 (Cꢀ2/Cꢀ
3/Cꢀ4/Cꢀ5/Cꢀ6), 76.9 (Cꢀ2/Cꢀ3/Cꢀ4/Cꢀ5/Cꢀ6), 76.2 (Cꢀ2/Cꢀ3/Cꢀ4/Cꢀ5/Cꢀ6), 75.3 (PhCH2O), 75.2
(PhCH2O), 73.4 (PhCH2O), 72.8 (Cꢀ2/Cꢀ3/Cꢀ4/Cꢀ5/Cꢀ6), 71.7 (Cꢀ2/Cꢀ3/Cꢀ4/Cꢀ5/Cꢀ6), 69.3 (Cꢀ
7), 58.7 (OCH3), 39.2 (C(CH3)3), 27.1 (C(CH3)3); HRMS (ESI) Calc. for (M + Na) C34H42NaO8:
601.2772. Found 601.2768. Data for 15a: (~2:1 α/β mixture) clear oil. Rf 0.63 & 0.57 (2:1
hexanes–EtOAc); 1H NMR (498 MHz; CDCl3): δ 7.38–7.28 (m, 30H, Ar), 5.38 (d, 0.67H, J = 3.7
Hz, Hꢀ1α), 4.94 (d, 0.67H, J = 11.1 Hz, PhCH2O), 4.93–4.78 (m, 3.33H, Hꢀ2α, Hꢀ2β, 5 ×
PhCH2O), 4.66 (d, 1H, J = 11.2 Hz, 2 × PhCH2O), 4.60 (d, 0.67H, J = 12.0 Hz, PhCH2O), 4.59
(d, 0.67H, J = 12.1 Hz, PhCH2O), 4.55 (d, 0.33H, J = 11.9 Hz, PhCH2O), 4.51 (d, 0.67H, J =
12.0 Hz, PhCH2O), 4.51 (d, 0.33H, J = 8.3 Hz, Hꢀ1β), 4.11 (dd, 0.67H, J = 9.5, 9.5 Hz, Hꢀ3α),
4.05 (dd, 0.67H, J = 10.0, 1.4 Hz, Hꢀ5α), 3.92 (dd, 0.33H, J = 9.7, 9.0 Hz, Hꢀ4β), 3.87–3.73 (m,
3.33H, Hꢀ3β, Hꢀ4α, Hꢀ6α, Hꢀ6β, Hꢀ7α, Hꢀ7β, Hꢀ7’β), 3.67 (dd, 0.676H, J = 9.7, 6.3 Hz, Hꢀ7’α),
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3.55 (dd, 0.33H, J = 9.8, 1.4 Hz, Hꢀ5β), 3.48 (s, 3H, 2 × OCH3), 1.23 (s, 9H, 2 × C(CH3)3); C
NMR (126 MHz; CDCl3): δ 179.2 (C=O), 177.8 (C=O), 138.4 (2C, Ar, Ar), 138.2 (2C, Ar, Ar),
138.1 (Ar), 138.0 (Ar), 128.5 (2C, Ar, Ar), 128.4 (3C, Ar, Ar, Ar), 128.1 (2C, Ar, Ar), 127.8 (2C,
Ar, Ar), 127.9 (Ar), 127.7 (3C, Ar, Ar, Ar), 127.6 (Ar), 127.5 (Ar), 127.4 (Ar), 96.6 (Cꢀ1β), 90.3
(Cꢀ1α), 82.8 (Cꢀ3β), 80.1 (Cꢀ3α), 77.3, 77.1, 76.3, 76.2, 76.1, 75.3 (PhCH2O), 75.1 (PhCH2O),
74.9 (3C, Cꢀ5β, 2 × PhCH2O), 74.0, 73.5 (PhCH2O), 73.3 (PhCH2O), 70.0 (Cꢀ5α), 69.3 (2C, Cꢀ
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7α, Cꢀ7β), 58.9 (OCH3), 58.8 (OCH3), 39.0 (C(CH3)3), 38.8 (C(CH3)3), 27.2 (C(CH3)3), 27.1
(C(CH3)3); HRMS (ESI) Calc. for (M + Na) C34H42NaO8: 601.2772. Found 601.2769.
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pꢀTolyl
3,4,7ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀmethylꢀ2ꢀOꢀpivloylꢀ1ꢀthioꢀ
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ꢀglyceroꢀβꢀ ꢀglucoꢀ
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heptopyranoside (16). To 15b (799 mg, 1.38 mmol) in anhydrous pyridine (7.5 mL) under argon
were sequentially added (TolS)2 (680 mg, 2.76 mmol) and 1M P(CH3)3 in THF (2.76 mL, 2.76
mmol). The reaction mixture was stirred for 21 h and then poured over a solution of brine (5 mL)
and H2O (5 mL) and then extracted with EtOAc (2 × 40 mL). The organic layers were combined,
dried over Na2SO4, filtered and concentrated. The resulting residue was purified by flash
chromatography (dry loading) in 4:1 hexanes–EtOAc to afford 16 (850 mg, 90%) as a pale
yellow viscous oil. Rf 0.56 (3:1 hexanes–EtOAc); [α]D –9.7 (1.0 c, CHCl3); 1H NMR (498 MHz;
CDCl3): δ 7.39–7.26 (m, 17H, Ar), 7.04 (d, 2H, J = 7.9 Hz, Ar), 5.15 (dd, 1H, J = 10.1, 9.2 Hz,
Hꢀ2), 4.89 (d, 1H, J = 11.0 Hz, PhCH2O), 4.77 (d, 1H, J = 11.0 Hz, PhCH2O), 4.73 (d, 1H, J =
11.0 Hz, PhCH2O), 4.65 (d, 1H, J = 11.0 Hz, PhCH2O), 4.57 (d, 1H, J = 10.2 Hz, Hꢀ1), 4.44 (d,
1H, J = 11.8 Hz, PhCH2O), 4.42 (d, 1H, J = 11.8 Hz, PhCH2O), 3.94 (dd, 1H, J = 9.4, 9.4 Hz, Hꢀ
4), 3.83–3.80 (m, 2H, Hꢀ6, Hꢀ7a), 3.78 (dd, 1H, J = 9.1, 9.1 Hz, Hꢀ3), 3.63 (dd, 1H, J = 11.5, 9.1
Hz, Hꢀ7b), 3.51 (dd, 1H, J = 9.8, 1.7 Hz, Hꢀ5), 3.46 (s, 3H, OCH3), 2.29 (s, 3H, (ArCH3)), 1.26
(s, 9H, C(CH3)3); 13C NMR (126 MHz; CDCl3): δ 176.8 (C=O), 138.3 (Ar), 138.1(4) (Ar),
138.1(1) (Ar), 137.8 (Ar), 132.7 (Ar), 130.4 (Ar), 129.6 (Ar), 128.4 (3C, Ar, Ar, Ar), 127.7 (2C,
Ar, Ar), 127.6 (2C, Ar, Ar), 127.5 (Ar), 127.4 (Ar), 88.2 (Cꢀ1), 85.1 (Cꢀ3), 78.6 (Cꢀ5), 76.9 (Cꢀ
4), 76.2 (Cꢀ6), 75.1 (PhCH2O), 74.9 (PhCH2O), 73.4 (PhCH2O), 72.0 (Cꢀ2), 68.9 (Cꢀ7), 58.4
(OCH3), 38.8 (C(CH3)3), 27.2 (C(CH3)3), 21.1 (ArCH3); HRMS (ESI) Calc. for (M + NH4)
C41H52NO7S: 702.3459. Found 702.3445.
pꢀTolyl 2,3,4,7ꢀtetraꢀOꢀbenzylꢀ6ꢀOꢀmethylꢀ1ꢀthioꢀ
D
ꢀglyceroꢀβꢀ ꢀglucoꢀheptopyranoside (1).
L
To 16 (800 mg, 1.17 mmol) in anhydrous DMF (12 mL) under argon were sequentially added
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BnBr (280 ꢁL, 2.34 mmol) and NaH (94 mg, 2.34 mmol). The reaction mixture was stirred for
0.5 h, then heated to 60 °C and stirred for another 3 h. The mixture was then cooled to room
temperature and additional NaH (94 mg, 2.34 mmol) was added before the mixture was heated
again 60 °C and stirred for another 3 h. After cooling to room temperature, excess NaH was
quenched by addition of CH3OH (~1 mL). The mixture was then concentrated. The residue was
diluted with EtOAc (100 mL) and washed with a solution of brine (20 mL) and then H2O (20
mL). The organic layer was dried over Na2SO4, filtered, and concentrated. The resulting residue
was purified by flash chromatography (dry loading) in 10:1→4:1 hexanes–EtOAc to afford 1
(575 mg, 71%, 95% based on recovered 16 and substrate lacking Piv group) as a pale yellow
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viscous oil. Obtained [α]D –17.8 (0.7 c, CHCl3); reported [α]D –15.9 (0.7 c, CHCl3); H and C
NMR data matched that reported previously.
1
Supporting Information Available. H and 13C NMR spectra for compounds 9, 13, 14, 15a,
15b, and 16.
Corresponding Author
*Eꢀmail: tlowary@ualberta.ca (T.L.L.)
Notes
The authors declare no competing financial interest.
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Acknowledgment. This work is supported by the Alberta Glycomics Centre and Natural
Sciences and Engineering Research Council of Canada. R.A.A. thanks Alberta Innovates Health
Solutions and Alberta Innovates Technology Futures for graduate student scholarships.
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References:
(1) Sherman, P. M.; Ossa, J. C.; Wine, E. Curr. Opin. Gastroenterol. 2010, 26, 1−4.
(2) Pithadia, A. B.; Kakadia, N. Pharmacol. Rep. 2010, 62, 220−232.
(3) Mishu, B.; Blaser, M. J. Clin. Infect. Dis. 1993, 17, 104−108.
(4) Guerry, P.; Szymanski, C. M. Trends Microbiol. 2008, 16, 428−435.
(5) Bacon, D. J.; Szymanski, C. M.; Burr, D. H.; Silver, R. P.; Alm, R. A.; Guerry, P. Mol.
Microbiol. 2001, 40, 769−777.
(6) Guerry, P.; Poly, F.; Riddle, M.; Maue, A. C.; Chen, Y.ꢀH.; Monteiro, M. A. Front. Cell.
Infect. Microbiol. 2012, 2, 1−11.
(7) Monteiro, M. A.; Baqar, S.; Hall, E. R.; Chen, Y.ꢀH.; Porter, C. K.; Bentzel, D. E.;
Applebee, L.; Guerry, P. Infect. Immun. 2009, 77, 1128−1136.
(8) Poulin, M. B.; Nothaft, H.; Hug, I.; Feldman, M. F.; Szymanski, C. M.; Lowary, T. L. J.
Biol. Chem. 2010, 285, 493−501.
(9) Poulin, M. B.; Shi, Y.; Protsko, C.; Dalrymple, S. A.; Sanders, D. A. R.; Pinto, B. M.;
Lowary, T. L. ChemBioChem 2014, 15, 47−56.
(10) Michael, F. S.; Szymanski, C. M.; Li, J.; Chan, K. H.; Khieu, N. H.; Larocque, S.;
Wakarchuk, W. W.; Brisson, J.ꢀR.; Monteiro, M. A. Eur. J. Biochem. 2002, 269,
5119−5136.
(11) Szymanski, C. M.; Michael, F. S.; Jarrell, H. C.; Li, J.; Gilbert, M.; Larocque, S.;
Vinogradov, E.; Brisson, J.ꢀR. J. Biol. Chem. 2003, 278, 24509−24520.
(12) Peng, W.; Jayasuriya, A. B.; Imamura, A.; Lowary, T. L. Org. Lett. 2011, 13, 5290−5293.
(13) Takeuchi, M.; Taniguchi, T.; Ogasawara, K. Synthesis 1999, 2, 341−354.
(14) Harris, J. M.; Keränen, M. D.; Nguyen, H.; Young, V. G.; O'Doherty, G. A. Carbohydr.
Res. 2000, 328, 17−36.
(15) Ahmed, M. M.; Berry, B. P.; Hunter, T. J.; Tomcik, D. J.; O'Doherty, G. A. Org. Lett.
2005, 7, 745−748.
(16) Babu, R. S.; O'Doherty, G. A. J. Am. Chem. Soc. 2003, 125, 12406−12407.
(17) Shan, M.; Xing, Y.; O'Doherty, G. A. J. Org. Chem. 2009, 74, 5961−5966.
(18) Taniguchi, T.; Ohnishi, H.; Ogasawara, K. Chem. Commun. 1996, 1477−1478.
(19) Lee, D.; Williamson, C. L.; Chan, L.; Taylor, M. S. J. Am. Chem. Soc. 2013, 134,
8260−8267.
(20) Chan, L.; Taylor, M. S. Org. Lett. 2011, 13, 3090−3093.
(21) Nicolaou, K. C.; Cole, K. P.; Frederick, M. O.; Aversa, R. J.; Denton, R. M. Angew. Chem.
Int. Ed. 2007, 46, 8875−8879.
(22) Corey, E. J.; Kigoshi, H. Tetrahedron Lett. 1991, 32, 5025−5028.
(23) Balachari, D.; O'Doherty, G. A. Org. Lett. 2000, 2, 4033−4036.
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