Remote participation-assisted synthesis of β-mannosides

Article abstract of DOI:10.1002/ejoc.200400616

The stereoselectivity of β-mannosylation can be improved with the use of a participating moiety at C-4 (O-anisoyl, O-thiocarbamoyl). This improvement was achieved in glycosidations of S-ethyl and, especially, S-benzoxazolyl (SBox) mannosides. Wiley-VCH Ve

Full text of DOI:10.1002/ejoc.200400616

FULL PAPER
Remote Participation-Assisted Synthesis of β-Mannosides
Cristina De Meo,[a] Medha N. Kamat,[a] and Alexei V. Demchenko*[a]
Keywords: Carbohydrates / Glycosylation / Remote participation / Stereoselective synthesis
The stereoselectivity of β-mannosylation can be improved
with the use of a participating moiety at C-4 (O-anisoyl, O-
thiocarbamoyl). This improvement was achieved in glycosid-
ations of S-ethyl and, especially, S-benzoxazolyl (SBox) man-
nosides.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
S-Ethyl glycosides, which have proven to be excellent gly-
cosyl donors, were initially employed in our studies.[42,43] In
order to investigate the remote effect on β-mannosylation,
we obtained two thiomannosides modified at position C-4:
1a (p-methoxybenzoyl, anisoyl) and 1b (N,N-diethylthiocar-
bamoyl, Scheme 1). Their synthesis was accomplished by
simple acylation (anisoyl chloride/pyridine or Et2NCSCl/
NaH/DMF, respectively) of the known 4-OH precursor
1c.[44] It is noteworthy that both the anisoyl[45] and thiocar-
bamoyl[46,47] moieties have already been tested as remote
participating groups on other sugar models.
For comparison, ethyl-2,3,4,6-tetra-O-benzyl-1-thio-α-d-
mannopyranoside (1d)[48] was used. Also, it has been pre-
viously documented that the 4,6-O-benzylidene acetal helps
to improve the stereoselectivity of β-mannosylation by con-
formational modification of the transition state.[15,49] For
this purpose we included ethyl-2,3-di-O-benzyl-4,6-O-ben-
zylidene-1-thio-α-d-mannopyranoside (1e)[44] in our com-
parative studies. On the other hand, compounds 2 and 3 [50]
were selected as suitable glycosyl acceptors.
Introduction
The majority of carbohydrates found in nature exist as
polysaccharides, glycoconjugates or glycosides in which
monosaccharide units are connected by glycosidic
bonds.[1–5] The necessity to form either a 1,2-cis- or 1,2-
trans-glycosidic bond with complete stereoselectivity is the
main reason chemical O-glycosylation is considered among
the greatest challenges of modern synthetic chemistry. To
address these issues, many new synthetic methodologies and
strategies have been developed.[6–8] However, all of these de-
velopments are compromised when applied to the stereose-
lective synthesis of 1,2-cis-glycosides,[9–11] among which β-
mannosides stand out as a particular challenge.[12–14] As a
result, the synthesis of natural glycostructures containing
one or more linkages of this type is problematic. Despite
significant efforts and considerable progress made in the
area of stereoselective β-mannosylation by Crich[15–20] and
others,[21–41] each particular case still requires careful selec-
tion of techniques, protecting groups, promoters and syn-
thetic strategies.
Having analysed possible mechanistic pathways, we as-
sumed that upon promoter-assisted departure of the leaving
group (S-ethyl), oxacarbenium ion A will be formed
(Scheme 1). Subsequently, it is quite possible that participa-
tion would occur via acyloxonium ion B. It should be noted
Results and Discussion
As a part of a program to develop novel methods for the that in support of the feasibility of such a pathway, cyclic
synthesis of 1,2-cis-glycosides, we report here our attempt orthoesters (1,4- and 1,2,4-) of the d-gluco series have been
to address the synthetic challenges associated with stereose- isolated and characterised.[51–54] Presumably, in order to fa-
lective β-mannosylation. We decided to investigate whether cilitate the remote participation, the oxacarbenium ion
a participating moiety (ester or thioester group) capable of- might have to first adopt a different pyranose ring confor-
donation of a lone pair of electrons from the remote posi- mation (such as AЈ ).
tion of C-4 of the glycosyl donor would influence the ste-
reochemical outcome of mannosylations.
Glycosidation of the perbenzylated 1d was performed
under standard reaction conditions for the thioglycoside ac-
tivation[42,43] with the use of NIS/TMSOTf as a promoter
and molecular sieves (4 Å) in DCM. As anticipated, coup-
ling of 1d with either 2 or 3 preferentially afforded the α-
linked products 4 and 5, respectively. These results are listed
in Table 1 (entries 1 and 2). We found that this result could
[a]
Department of Chemistry & Biochemistry,
University of Missouri – St. Louis,
One University Boulevard, St. Louis, Missouri 63121-4499, USA
Fax: (internat.) +1-314-516-5342
E-mail: demchenkoa@umsl.edu
706
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/ejoc.200400616
Eur. J. Org. Chem. 2005, 706–711

Remote Participation-Assisted Synthesis of β-Mannosides
FULL PAPER
Scheme 1.
be slightly improved in terms of β-stereoselectivity by low- participation from the C-4 position. For these studies we
ering the reaction temperature to –70 °C (entry 3). Varying selected a fairly bulky S-benzoxazolyl (SBox) anomeric
other reaction conditions such as the promoter (MeOTf, moiety recently developed in our laboratory.[55,56] The ade-
DMTST, IDCP) and/or solvent (MeCN, DCM/ether, quately protected glycosyl donor 11a (Scheme 2) was ob-
DCM/toluene) did not result in significant improvements in tained from the corresponding S-ethyl glycoside 1a via bro-
stereoselectivity. As initially anticipated, the glycosyl donor mination with Br2 followed by treatment with KSBox in the
1e appeared to be more β-stereoselective. Thus, preferential presence of 18-crown-6 in 58 % yield after two steps. This
formation of the β-linked disaccharides 6 and 7 was de- is a typical procedure for the synthesis of the SBox glyco-
tected in these experiments (entries 4 and 6).
sides.[56] Similarly, the perbenzylated SBox mannoside 11c
was synthesised in 79% yield from 1d to be used for com-
parison. Unfortunately, our efforts to obtain 11b from 1b
according to this two-step pathway resulted in very low yi-
elds (15–20%). Therefore, we decided to explore the pos-
sibility of its direct synthesis from thioglycoside 11b in the
presence of a mild thiophilic promoter. This transformation
was successfully achieved with HSBox in the presence of
iodonium(dicollidine) perchlorate[57] and molecular sieves
(4 Å). As a result, 11b was obtained from 1b in 49% yield.
Table 1. NIS/TMSOTf-promoted glycosidations of the SEt manno-
sides 1a, b, e, d in CH2Cl2.
En- Do- Acc.
try nor
Temperature
Pro- Yield, % α/β ra-
duct
tio
1
1d
2
3
3
2
3
3
2
3
3
room temp.
room temp.
–70 Ǟ 0 °C
room temp.
room temp.
–70 °C
room temp.
room temp.
–70 °C Ǟ room
temp.
4
5
5
6
7
7
8
9
9
86
98
99
98
99
99
99
63
90
2.7:1
1.6:1
1.3:1
1:1.4
1.2:1
1:2.1
1.6:1
1.2:1
1:1.5
2
3
4
5
6
7
8
9
1d
1d
1e
1e
1e
1a
1a
1a
10
11
1b
1b
3
3
room temp.
–70 °C Ǟ room
temp.
10
10
63
64
1:1.1
1:1.5
Subsequently, we turned our attention to the glycosid-
Scheme 2.
ation of mannosyl donors 1a and 1b bearing participating
moieties at C-4. Unfortunately, the new mannosyl donors
were only slightly β-stereoselective at low temperatures. In
Initial experiments with perbenzylated SBox glycoside
this respect, the thiocarbamoyl moiety allowed a marginally 11c were rather discouraging since no significant improve-
higher stereoselectivity at room temperature. Although ment was observed in comparison with that of S-ethyl man-
some improvement was achieved in facilitating the acyl- noside 1d. These results are presented in Table 2 (entries 1
oxonium ion B formation, the pyranose chair flip (A Ǟ and 2). Conversely, to our delight, SBox glycosyl donors
AЈ , Scheme 1) does not seem to be a favoured pathway for bearing the anisoyl and thiocarbamoyl participating groups
the thioglycosides of the d-manno series.
11a and 11b, respectively, provided relatively high stereo-
We reasoned that if a sterically bulky leaving group were selectivities, thus providing encouraging support for the re-
placed in the axial position at the anomeric centre, the 1,3- mote participation concept. As listed in Table 2, these reac-
diaxial interactions would facilitate the chair in adopting a tions were performed in CH2Cl2 at low temperature (–70 °C
1
C
conformation and would therefore favour subsequent Ǟ room temp.). Interestingly, a number of promoters avail-
4
Eur. J. Org. Chem. 2005, 706–711
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
707

C. De Meo, M. N. Kamat, A. V. Demchenko
FULL PAPER
able for the activation of the SBox-functionality such as Ag- and l-fuco[62,63] series. Initially, this influence was attributed
OTf, MeOTf or NIS/TMSOTf provided consistent β-stereo- to the electron-withdrawing effect of an ester group at a
selectivity with a respectable ratio α/β = 1:3–5 (entries 3–7, remote position.[64,65] As more experimental data has been
Table 2).
acquired, the importance of remote participation has come
to the foreground. For example, it has been previously dem-
onstrated that for the glycosyl donors of the d-galacto
series, an electron-withdrawing substituent at C-4 which is
not capable of participation, such as 2,2,2-trifluoroethyl,
does not affect the stereoselectivity. Conversely, remote
groups capable of participation have a dramatic effect.[45]
In the present work the improvement was especially notable
when a bulky SBox substituent was used as the leaving
group at the anomeric centre.
Table 2. Glycosidation of the SBox mannosides 11a–c with glycosyl
acceptors 3, 12–14 in CH2Cl2.
En-
try
Do-
nor
Acc.
Promoter
Prod- Yield, % α/β ra-
uct
tio
1
11c
3
AgOTf
5
5
9
9
9
65
72
83
96
57
1:1.5
1:2.2
1:3.1
1:3.5
1:3.2
2
3
4
5
11c
11a
11a
11a
3
3
3
3
MeOTf
AgOTf
MeOTf
NIS/
TMSOTf
AgOTf
NIS/
TMSOTf
MeOTf
MeOTf
MeOTf
MeOTf
MeOTf
MeOTf
6
7
11b
11b
3
3
10
10
82
66
1:4.9
1:3.3
Experimental Section
General Remarks: Column chromatography was performed on sil-
ica gel 60 (EM Science, 70–230 mesh), reactions were monitored
by TLC on Kieselgel 60 F254 (EM Science). The compounds were
detected by examination under UV light and by charring with 10%
sulfuric acid in methanol. Solvents were removed under reduced
pressure at Ͻ40 °C. DCM, MeNO2 and MeCN were distilled from
CaH2 immediately prior to use. Anhydrous DMF (EM Science)
was used as received. Methanol was dried by heating to reflux with
magnesium methoxide, distilled and stored under argon. Pyridine
was dried by heating to reflux with CaH2 and then distilled and
stored over molecular sieves (3 Å). Molecular sieves (3 Å), used for
reactions, were crushed and activated in vacuo at 390 °C over 8 h
in the first instance and then for 2–3 h at 390 °C directly before
8
9
10
11
12
13
11c
11a
11c
11a
11c
11a
12
12
13
13
14
14
15
16
17
18
19
20
83
76
83
69
72
59
1:5.9
1:7.0
1:2.5
1:3.0
1:2.3
1:2.7
[a] AgOTf or NIS/TMSOTf-promoted glycosylations were initiated
at –70 °C, whereas MeOTf-promoted reactions were initiated at –
20 °C, the temperature was then allowed to gradually increase to
room temperature.
Subsequently, we turned our attention to the glycosyla-
tion of a range of secondary glycosyl acceptors 12–14 (Fig- use. AgOTf (Acros) was coevaporated with toluene (3× 10 mL) and
ure 1).[58–60] These experiments were performed under stan-
dried in vacuo for 2–3 h directly prior to application. Optical rota-
tions were measured on a Jasco P-1020 polarimeter. 1H NMR spec-
dard reaction conditions in the presence of MeOTf. As a
result, disaccharides 15–20 (Figure 1) were obtained with
tra were recorded at 300MHz and 13C NMR spectra were recorded
at 75MHz (Bruker Avance instrument). HRMS measurements were
high stereoselectivities and yields (Table 2, entries 8–13).
made with a JEOL MStation (JMS-700) Mass Spectrometer.
Synthesis of Glycosyl Donors
Ethyl 2,3,6-Tri-O-benzyl-4-O-(p-methoxybenzoyl)-1-thio-α-D-man-
nopyranoside (1a): Anisoyl chloride (2.03 mmol, 277 µL) was added
dropwise to a stirred solution of ethyl-2,3,6-tri-O-benzyl-1-thio-α-
d-mannopyranoside (1c, 300 mg, 0.61 mmol) in pyridine (2.0 mL)
under argon. The reaction mixture was kept for 16 h at room tem-
perature, quenched with MeOH (5 mL) and concentrated in vacuo.
The residue was coevaporated with toluene (3× 15 mL) and puri-
fied by silica gel column chromatography (ethyl acetate/hexane gra-
dient elution) to afford 1a as a colourless syrup (300 mg, 79%). Rf
= 0.50 (ethyl acetate/toluene, 1:9, v/v). [α]2D2 = +44.0 (c = 1.0,
CHCl3). 1H NMR (300 MHz, CDCl3): δ = 6.89–7.96 (m, 19 H,
aromatic), 5.62 (dd, J4,5 = 9.7 Hz,1 H, H-4), 5.42 (br. s, 1 H, H-1),
4.72 (s, 2 H, CH2Ph), 4.49 (s, 2 H, CH2Ph), 4.46 (dd, 2 J = 12.2 Hz,
2 H, CH2Ph), 4.32 (m, J5,6a = 6.2, J5,6b = 3.1 Hz, 1 H, H-5), 3.95
(m, 1 H, CH2 aCH3), 3.84–3.91 (m, J3,4 = 8.7 Hz, 2 H, H-2,3),
3.86–3.91 (m, 5 H, H-2,3, OCH3), 3.67 (dd, J6a,6b = 11.0 Hz, 1 H,
H-6a), 3.62 (dd, 1 H, H-6b), 2.65 (m, 2 H, CH2CH3), 1.28 (t, 3 H,
CH2CH3)ppm. 13C NMR (75 MHz, CDCl3): δ = 163.66, 138.37,
138.23, 137.99, 132.13, 128.56, 128.48, 128.35, 128.16, 128.06,
127.87, 127.81, 127.72, 127.52, 113.77, 82.32, 77.43, 76.03, 73.60,
Figure 1. Structures of the glycosyl acceptors 12–14 and disaccha-
rides 15–20.
Conclusions
In conclusion, these results demonstrate that the stereo-
selectivity of β-mannosylation can be improved with the use 72.57, 71.90, 71.17, 70.05, 69.40, 55.69, 25.46, 15.07 ppm. HR-FAB
MS [M + H]+ calcd. for C37H41O7S 629.2573, found 629.2571
of a participating moiety at C-4 for compounds of the d-
manno series. Previously, similar long-range participation
Ethyl 2,3,6-Tri-O-benzyl-4-O-(N,N-diethylthiocarbamoyl)-1-thio-α-
-mannopyranoside (1b): NaH (60%, 32 mg, 0.40 mmol) was added
has been demonstrated for sugars of the d-galacto[45,47,61]
D
708
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2005, 706–711

Remote Participation-Assisted Synthesis of β-Mannosides
FULL PAPER
portionwise to a stirred solution of 1c (200 mg, 0.80 mmol) and
N,N-diethylthiocarbamoyl chloride (92 mg, 0.60 mmol) in DMF
(2.0 mL) at 0 °C. The temperature was allowed to gradually rise to
room temperature and the reaction mixture was stirred for 16 h. It
wasthen poured into ice-water (50 mL) and stirred for an additional
30 min. The aqueous layer was extracted with ethyl acetate/Et2O
(1:1, v/v, 3× 15 mL). The organic layers were combined and washed
with water (3× 20 mL), dried (MgSO4) and concentrated in vacuo
to dryness. The residue was purified by silica gel column chroma-
tography (ethyl acetate/hexane gradient elution) to afford 1b as a
white foam (208 mg, 84%). Rf = 0.56 (ethyl acetate/toluene, 1:9, v/
v). [α]2D2 = +48.9 (c = 1.0, CHCl3). 1H NMR (300 MHz, CDCl3): δ
lid removed by filtration and the residue washed with CH2Cl2.
Thefiltrates were combined (30 mL) and washed with 20% aq.
NaHCO3 (15 mL) and water (3× 10 mL). The organic phase was
separated, dried with MgSO4 and concentrated in vacuo. The resi-
due was purified by silica gel column chromatography (ethyl ace-
tate/toluene gradient elution) to afford 11b as a clear syrup in 49%
yield. Rf = 0.60 (ethyl acetate/toluene, 1:9, v/v). [α]2D2 –5.9 (c = 1.0,
CHCl3). 1H NMR (300 MHz, CDCl3): δ = 6.66–7.70 (m, 19 H,
aromatic), 6.37 (dd, J4,5 = 9.8 Hz, 1 H, H-4), 6.04 (d, J1,2 = 1.2 Hz,
1 H, H-1), 4.65 (dd, 2J = 11.9 Hz, 2 H, CH2Ph), 4.53 (dd, 2J =
12.2 Hz, 2 H, CH2Ph), 4.46 (m, 1 H, H-5), 4.44 (dd, 2 J = 11.5 Hz,
2 H, CH2Ph), 4.00 (m, 1 H, CH2 aCH3), 3.82–3.94 (m, J3,4
9.8 Hz, 2 H, H-2,3), 3.74 (d, J5,6a = J5,.6b = J6a,6b = 4.7 Hz, 2 H,
=
= 7.26–7.40 (m, 18 H, aromatic), 6.17 (dd, J4,5 = 8.7 Hz, 1 H, H-
4), 5.39 (d, J1,2 = 2.4 Hz, 1 H, H-1), 4.70 (dd, J = 12.4 Hz, 2 H, H-6a,6b), 3.63 (m, 1 H, CH2 bCH3), 3.38 (m, 1 H, CH2 aCH3), 3.18
2
CH2Ph), 4.56 (dd, 2J = 11.9 Hz, 2 H, CH2Ph), 4.54 (dd, 2J =
12.1 Hz, 2 H, CH2Ph), 4.31 (m, 1 H, H-5), 3.95 (m, 1 H, CH2
(m, 1 H, CH2 bCH3), 1.24 (m, 3 H, CH2CH3), 1.01 (t, 3 H,
CH2CH3)ppm. 13C NMR (75 MHz, CDCl3): δ = 187.02, 177.00,
aCH3), 3.84–3.91 (m, J3,4 = 8.7 Hz, 2 H, H-2,3), 3.74–3.77 (m, 2 147.21, 138.10, 137.80, 131.47, 128.70, 128.63, 128.54, 128.27,
H, H-6a,6b), 3.66 (m, 1 H, CH2 bCH3), 3.18–3.42 (m, 2 H,
128.04, 127.88, 127.79, 127.72, 124.81, 124.03, 115.96, 109.70,
CH2CH3), 2.70 (m, 1 H, CH2CH3), 1.31 (t, 3 H, CH2CH3), 1.23 (t, 87.20, 80.65, 78.18, 74.97, 74.21, 73.61, 72.57, 72.37, 69.72, 48.48,
3 H, CH2CH3), 1.02 (t, 3 H, CH2CH3)ppm. 13C NMR (75 MHz, 43.53, 13.66, 12.09 ppm. HR-FAB MS [M + H]+ calcd. for
CDCl3): δ = 186.92, 138.53, 138.24, 138.11, 128.48, 128.41, 128.35, C39H43N2O6S2 699.2563, found 699.2567
128.11, 127.80, 127.74, 127.67, 127.54, 81.71, 75.94, 75.37, 74.30,
Benzoxazolyl 2,3,4,6-Tetra-O-benzyl-1-thio-α-D-mannopyranoside
73.47, 72.36, 71.83, 71.68, 70.10, 48.13, 43.34, 13.58, 12.03 ppm.
HR-FAB MS [M + H]+ calcd. for C34H44NO5S2 610.2661, found
610.2670
(11c): This was obtained from 1d, as described for the synthesis of
11a, as a colourless syrup in 79% yield. Rf = 0.60 (ethyl acetate/
toluene, 1:9, v/v). [α]2D2 –12.8 (c = 1.0, CHCl3). 1H NMR (300 MHz,
CDCl3): δ = 7.05–7.53 (m, 24 H, aromatic), 5.72 (d, J1,2 = 0.8 Hz,
1 H, H-1), 4.86 (dd, 2J = 11.4 Hz, 2 H, CH2Ph), 4.71 (s, 2 H,
CH2Ph), 4.65 (dd, 2J = 10.9 Hz, 2 H, CH2Ph), 4.47 (dd, 2J =
11.9 Hz, 2 H, CH2Ph), 4.12 (br. d, J2,3 = 1.2 Hz, 1 H, H-2), 3.97
(dd, J4,5 = 9.7 Hz, 1 H, H-4), 3.58–3.76 (m, 4 H, H-3,5,6a,6b)ppm.
13C NMR (75 MHz, CDCl3): δ = 163.27, 151.82, 141.71, 138.28,
138.16, 137.90, 137.81,128.52, 128.32, 128.27, 128.25, 128.17,
127.94, 127.88, 127.77, 127.64, 127.37, 124.33, 124.07, 118.61,
110.01, 84.65, 83.64, 80.52, 76.76, 76.58, 75.07, 74.92, 74.43, 73.44,
72.98, 69.07 ppm. HR-FAB MS [M + H]+ calcd. for C41H40NO6S
674.2576, found 674.2574.
Benzoxazolyl 2,3,6-Tri-O-benzyl-4-O-(p-methoxybenzoyl)-1-thio-α-
D-mannopyranoside (11a): A solution of 1a (300 mg, 0.477 mmol)
in CH2Cl2 (7.0 mL) together with activated molecular sieves (3 Å,
240 mg) was stirred under argon for 1 h. A freshly prepared solu-
tion of Br2 in CH2Cl2 (4.5 mL, 1:165, v/v) was then added and the
reaction mixture was kept for 5 min at room temp. After this, the
solid was removed by filtration and the filtrate was concentrated in
vacuo at room temp. The crude residue was then treated with
KSBox (0.57 mmol) and 18-crown-6 (0.04 mmol) in dry acetone
(5.0 mL) under argon for 2 h at room temp. Upon completion the
mixture was diluted with toluene, the solid removed by filtration
and the residuewashed with toluene. Thefiltrates(30 mL) were com-
bined and washed with 1% aq. NaOH (15 mL) and water (3×
10 mL). The organic layer was separated, dried with MgSO4 and
concentrated in vacuo. The residue was purified by silica gel col-
umn chromatography (ethyl acetate/toluene gradient elution) to af-
ford 11a as a colourless syrup (200 mg, 58%). Rf = 0.50 (ethyl ace-
tate/toluene, 1:9, v/v). [α]2D2–12.2 (c = 1.0, CHCl3). 1H NMR
(300 MHz, CDCl3): δ = 6.91–7.96 (m, 23 H, aromatic), 5.90 (d, J1,2
Synthesis of Disaccharides
Typical AgOTf-Promoted Glycosylation Procedure (Activation of
the SBox Glycosides 11a–c):
A mixture the glycosyl donor
(0.11 mmol), glycosyl acceptor (0.10 mmol) and freshly activated
molecular sieves (3 Å, 200 mg) in CH2Cl2 (2 mL) was stirred under
argon for 1.5 h. The reaction mixture was cooled to –70 °C and
freshly conditioned AgOTf (0.22 mmol) was added. The tempera-
ture was then allowed to gradually increase to room temperature
and the reaction mixture was stirred for 1–16 h. Upon completion,
the reaction mixture was diluted with CH2Cl2, the solid removed
by filtration and the residue washed with CH2Cl2. The filtrates were
combined (30 mL) and washed with 20% aq. NaHCO3 (15 mL)
and water (3× 10 mL). The organic phase was then separated, dried
with MgSO4 and concentrated in vacuo. The residue was purified
by silica gel column chromatography (ethyl acetate/hexane gradient
elution).
2
= 1.3 Hz, 1 H, H-1), 5.69 (dd, J4,5 = 9.5 Hz, 1 H, H-4), 4.96 (dd,
2
J = 11.5 Hz, 2 H, CH2Ph), 4.65 (dd, J = 12.2 Hz, 2 H, CH2Ph),
4.44 (dd, J = 11.7 Hz, 2 H, CH2Ph), 4.25 (br. d, H-2), 3.83–4.00
2
(m, J3,4 = 9.5 Hz, 2 H, H-3,5), 3.89 (s, 3 H, OCH3), 3.71 (d, J5,6a
= J5,.6b = J6a,6b = 4.8 Hz, 2 H, H-6a,6b)ppm. 13C NMR (75 MHz,
CDCl3): δ = 163.77, 152.06, 141.85, 138.11, 137.62, 137.47, 132.08,
128.81, 128.64, 128.51, 128.24, 128.12, 128.07, 127.84, 127.46,
124.59, 124.35, 122.23, 118.81, 113.84, 110.26, 84.76, 80.38, 79.48,
75.80, 74.97, 73.66, 72.67, 70.05, 68.89, 55.67 ppm. HR-FAB MS
[M + H]+ calcd. for C42H40NO8S 718.2475, found 718.2480
Typical MeOTf-Promoted Glycosylation Procedure (Activation of
Benzoxazolyl 2,3,6-Tri-O-benzyl-4-O-(N,N-diethylthiocarbamoyl)-1-
the SBox Glycosides 11a–c): A mixture the glycosyl donor
thio-α-
D
-mannopyranoside (11b):
A
mixture of 1b (44.3 mg,
(0.11 mmol), glycosyl acceptor (0.10 mmol) and freshly activated
molecular sieves (3 Å, 200 mg) in CH2Cl2 (2 mL) was stirred under
argon for 1.5 h. The reaction mixture was cooled to –20 °C and
MeOTf (0.33 mmol) was added. The temperature was then allowed
to gradually increase to room temperature and the reaction mixture
was stirred for 1–16 h. Upon completion, the reaction mixture was
diluted with CH2Cl2, the solid removed by filtration and the residue
washed with CH2Cl2. The filtrates were combined (30 mL) and
0.073 mmol), HSBox (21 mg, 0.145 mmol) and freshly activated
molecular sieves (4 Å, 120 mg) in CH2Cl2 (2 mL) was stirred under
argon for 1.5 h. The reaction mixture was then cooled to 0 °C and
iodonium(dicollidine)perchlorate (102 mg, 0.20 mmol) was added.
The temperature was then allowed to gradually increase to room
temperature and the reaction mixture was stirred for 24 h. Upon
completion, the reaction mixture was diluted with CH2Cl2, the so-
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709

C. De Meo, M. N. Kamat, A. V. Demchenko
FULL PAPER
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1
All synthesised disaccharides have appropriate H, 13C NMR and
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Acknowledgments
This work was supported by “The Foundation BLANCEFLOR
Boncompagni-Ludovisi, née Bildt” and the University of Missouri
Research Board. The authors also thank the NSF for grants to
purchase the NMR spectrometer (CHE-9974801) and the mass
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