Chemoselective synthesis of oligosaccharides of 2-deoxy-2-aminosugars

Article abstract of DOI:10.1021/jo062171d

(Chemical Equation Presented) Along with the application of the S-benzoxazolyl glycosides to the high-yielding synthesis of disaccharides of the 2-amino-2-deoxy series, chemoselective assembly of oligosaccharides containing multiple residues of 2-amino-2-

Full text of DOI:10.1021/jo062171d

glucosamine (GlcNAc) that is a component of fungal cell wall
and arthropod integuments,3 heparin, a linear sulfated poly-
sackecharide consisting of alternating GlcNAc and L-iduronic
acid units that is a major factor in diverse biological processes
including blood coagulation, viral infections, cell growth,
inflammation, etc.,4,5 and the lipid-A region of antigenic
lipopolysaccharides, an amphiphilic macromolecule composed
of two D-glucosamine residues that has been shown to affect a
variety of inflammatory processes.6,7 Multiple glycosamino
residues have also been found in a variety of tumor-associated
glycosphingolipids.8 Although it is now possible to selectively
cleave, isolate, purify, and characterize certain classes of natural
glycostructures, their accessibility in pure form is still limited.
As a result, methods for the synthesis of glycosides and
oligosaccharides containing 2-deoxy-2-amino residues have been
the focus of a considerable amount of research.9-11
Chemoselective Synthesis of Oligosaccharides of
2-Deoxy-2-aminosugars
Aileen F. G. Bongat, Medha N. Kamat, and
Alexei V. Demchenko*
Department of Chemistry and Biochemistry, UniVersity of
MissourisSt. Louis, One UniVersity BouleVard, St. Louis,
Missouri 63121
demchenkoa@umsl.edu
ReceiVed October 18, 2006
A vast majority of naturally occurring glycosamine residues
are N-acetylated and linked via a 1,2-trans (â-D-gluco/galacto)
linkage. However, it has been shown that glycosylation of
complex aglycones with glycosyl donors bearing a 2-acetamido-
2-deoxy functionality is usually impractical.9,11 Unlike the
reactive acyloxonium intermediate formed via participatory
assistance of the 2-O-acetyl moiety in neutral sugars (see
Scheme 1a), the 1,2-O,N-oxazoline intermediate (Scheme 1b)
formed during glycosidation of N-acetylated glucosamine
derivatives is rather stable. This significantly decreases the rate
of glycosylation and yields, especially if unreactive or sterically
hindered glycosyl acceptors are used.
As such, following the general theory that neighboring group
participation promotes efficient formation of 1,2-trans-linked
glycosides, various 2-amino substituents have already been
reported. These include N-trifluoroacetyl (trifluoroacetamido,
NHTFA),12 N-phthaloyl (phthalimido, NPhth),13,14 N-trichloro-
ethoxycarbonyl (trichloroethoxycarbamoyl, NHTroc),15 and
other substituents.16-25 In spite of a variety of classes of glycosyl
Along with the application of the S-benzoxazolyl glycosides
to the high-yielding synthesis of disaccharides of the
2-amino-2-deoxy series, chemoselective assembly of oli-
gosaccharides containing multiple residues of 2-amino-2-
deoxyglycoses is reported. This modified armed-disarmed
approach is relying on the observation that 2-N-trichloroet-
hoxycarbonyl derivatives of S-benzoxazolyl glycosides are
significantly more reactive than their 2-N-phthaloyl coun-
terparts in MeOTf-promoted glycosylations. This allowed
efficient chemoselective synthesis of 1,2-trans-linked oli-
gosaccharides, the disarmed reducing end of which can be
activated for immediate second step glycosidation in the
presence of a more powerful activator, AgOTf. As a result
of this two-step activation, trans-trans-patterned trisaccha-
rides could be assembled in a highly efficient manner. This
result differs from the classic armed-disarmed technique,
according to which usually cis-trans-patterned oligosac-
charides are generated.
(3) Synowiecki, J.; Al-khateeb, N. A. Crit. ReV. Food Sci. Nutr. 2003,
43, 145-171.
(4) Poletti, L.; Lay, L. Eur. J. Org. Chem. 2003, 2999-3024.
(5) Linhardt, R. J.; Toida, T. Acc. Chem. Res. 2004, 37, 431-438.
(6) Rossignol, D. P.; Hawkins, L. D.; Christ, W. J.; Kobayashi, S.;
Kawata, T.; Lynn, M.; Yamatsu, I.; Kishi, Y. In Endotoxin in Health and
Disease; Brade, H., Opal, S. M., Vogel, S. N., Morrison, D. C., Eds; Marcel
Dekker: New York. 1999; pp 699-717.
(7) Kusumoto, S.; Oikawa, M. In Glycoscience: Chemistry and Chemical
Biology; Fraser-Reid, B., Tatsuta, K., Thiem, J., Eds.; Springer: New York;
2001; Vol. 3, pp 2107-2148.
(8) Hakomori, S.; Zhang, Y. M. Chem. Biol. 1997, 4, 97-104.
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The involvement of complex glycostructures in the patho-
genesis of deadly diseases such as AIDS, cancer, pneumonia,
meningitis, and hepatitis is now well-recognized. This knowl-
edge has been translated into an appreciation of carbohydrates
as targets for modern therapeutics.1,2 Among a variety of
biologically important carbohydrates are the prokaryotic and
eukaryotic glycoconjugates, which are comprised mainly of
residues of the 2-amino-2-deoxy-â-D-glucopyranosyl (D-glu-
cosamino) series. Most representative examples include, but are
not limited to, chitin, a linear homopolymer of 2-acetamido-D-
(10) Debenham, J.; Rodebaugh, R.; Fraser-Reid, B. Liebigs Ann./Recl.
1997, 791-802.
(11) Bongat, A. F. G.; Demchenko, A. V. Carbohydr. Res. 2007, in press.
(12) Wolfrom, M. L.; Bhat, H. B. J. Org. Chem. 1967, 32, 1821-1823.
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39, 90-115.
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L. V. Tetrahedron 1985, 41, 3363-3375.
(15) Ellervik, U.; Magnusson, G. Carbohydr. Res. 1996, 280, 251-260.
(16) Debenham, J. S.; Madsen, R.; Roberts, C.; Fraser-Reid, B. J. Am.
Chem. Soc. 1995, 117, 3302-3303.
(17) Kwon, O.; Danishefsky, S. J. J. Am. Chem. Soc. 1998, 120, 1588-
1599.
(1) Carbohydrate-Based Drug DiscoVery; Wong, C. H., Ed.; Wiley: New
York, 2003.
(2) Carbohydrate Drug Design; Klyosov, A. A., Witczak, Z. J., Platt,
D., Eds.; American Chemical Society: Washington, DC, 2006; Vol. 932.
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(19) Castro-Palomino, J. C.; Schmidt, R. R. Tetrahedron Lett. 2000, 41,
629-632.
10.1021/jo062171d CCC: $37.00 © 2007 American Chemical Society
Published on Web 01/25/2007
1480
J. Org. Chem. 2007, 72, 1480-1483

SCHEME 1
donors tested in these glycosylations, the yields achieved in these
glycosylations are still far from being satisfactory.
already reported that benzoxazolyl derivatives of neutral sugars
can be activated with mildly electrophilic promoters such as
AgOTf, MeOTf, Cu(OTf)2, or NIS/TfOH.27,33 Also in applica-
tion to our new targets, 2-N-substituted glycosyl donors,
activations with either AgOTf or MeOTf gave the best outcome;
the key reactions are summarized in Table 1. Glycosyl donors
1-3 performed very well in each reaction attempted, affording
the corresponding disaccharide derivatives 9-12 in high yields
and complete stereoselectivity (Table 1). As anticipated, gly-
cosidation of 2-acetamido derivative 4 was sluggish and
incomplete even in prolonged experiments (16-48 h). This
reaction was negatively affected by the formation of a relatively
unreactive 1,2-oxazoline intermediate.
The initial purpose of the study reported herein was to
improve the yields for the introduction of 2-deoxy-2-N-
substituted-â-D-glucopyranosyl residues in oligosaccharides. We
assumed that this goal could be achieved by applying novel
thioimidoyl glycosidation methodology, the development of
which has been the primary focus of our research program.
Among the thioimidates investigated, we have already reported
that 1-S-benzoxazolyl (SBox) derivatives make excellent gly-
cosyl donors due to their accessibility, stability, and high
stereoselectivity and yields in glycosylations achieved under
mild activation conditions.26,27
We have also observed that, while AgOTf-promoted gly-
cosidations of 1-3 were complete in less than 15 min,
significantly different results have been recorded in MeOTf-
promoted glycosylations. Thus, we noted that typically 1-2 h
were required for glycosidation of NPhth (1) and NHTFA (3)
derivatives, whereas NHTroc glycosyl donor (2) could be
glycosidated in a matter of minutes (<5-15 min) under
essentially the same reaction conditions. Therefore, we antici-
pated that this observation could give rise to a complementary
glycosylation approach for chemoselective glycosidation of
2-aminosugars similar to that discovered by Fraser-Reid34 and
explored by others29,35,36 for the neutral sugars.
While a significant disparity in reaction rates between NPhth-
and NHTroc-protected derivatives has been observed,15,37 no
systematic studies have yet become available. The possibility
of chemoselective activation of NTroc-protected donors over
NPhth-protected acceptors for chemoselective oligosaccharide
synthesis has only been applied once by Baasov’s group in a
sequential one-pot oligosaccharide synthesis employing tolyl
thioglycosides.38 Another relevant report explores the chemose-
Nowadays, the majority of oligosaccharides are synthesized
in a convergent-selective or chemoselective fashion.28 Neverthe-
less, persistent attempts to apply these findings to 2-aminosugars
have yet to emerge. Therefore, the ultimate goal of these studies
would be the development of a chemoselective strategy for the
synthesis of oligosaccharides containing multiple sequential
residues of 2-amino-2-deoxysugars.
With these intentions in mind, we obtained four novel
N-substituted SBox glycosides 1-4 (Figure 1), among which
the 2-acetamido donor 4 was mainly intended for comparative
studies. These compounds were synthesized from either glycosyl
acetates with 2-mercaptobenzoxazole in the presence of a Lewis
acid or glycosyl halides, bromides or chlorides, by reaction with
2-benzoxazolethione, potassium or sodium salt in the presence
of a suitable crown ether, 18-crown-6 or 15-crown-5, respec-
tively. High yields in the range of 80-95% and complete
stereoselectivity were recorded for these transformations.
Having obtained SBox glycosides 1-4, which were found
to be stable crystalline or amorphous solids, we turned our
attention to investigating their glycosyl donor properties in
reactions with common glycosyl acceptors 5-8.29-32 We have
(29) Veeneman, G. H.; van Boom, J. H. Tetrahedron Lett. 1990, 31,
275-278.
(30) Garegg, P. J.; Hultberg, H. Carbohydr. Res. 1981, 93, C10-C11.
(31) Koto, S.; Takebe, Y.; Zen, S. Bull. Chem. Soc. Jpn. 1972, 45, 291-
293.
(20) Benakli, K.; Zha, C.; Kerns, R. J. J. Am. Chem. Soc. 2001, 123,
9461-9462.
(21) Donohoe, T. J.; Logan, J. G.; Laffan, D. D. P. Org. Lett. 2003, 5,
4995-4998.
(32) Sollogoub, M.; Das, S. K.; Mallet, J.-M.; Sinay, P. C. R. Acad. Sci.
1999, 2, 441-448.
(22) Barroca, N.; Schmidt, R. R. Org. Lett. 2004, 6, 1551-1554.
(23) Dahl, R. S.; Finney, N. S. J. Am. Chem. Soc. 2004, 126, 8356-
8357.
(33) Kamat, M. N.; Demchenko, A. V. Org. Lett. 2005, 7, 3215-3218.
(34) Mootoo, D. R.; Konradsson, P.; Udodong, U.; Fraser-Reid, B. J.
Am. Chem. Soc. 1988, 110, 5583-5584.
(24) Arihara, R.; Nakamura, S.; Hashimoto, S. Angew. Chem., Int. Ed.
2005, 44, 2245-2249.
(35) Douglas, N. L.; Ley, S. V.; Lucking, U.; Warriner, S. L. J. Chem.
Soc., Perkin Trans. 1 1998, 51-65.
(25) Boysen, M.; Gemma, E.; Lahmann, M.; Oscarson, S. Chem.
Commun. 2005, 3044-3046.
(36) Zhang, Z.; Ollmann, I. R.; Ye, X. S.; Wischnat, R.; Baasov, T.;
Wong, C. H. J. Am. Chem. Soc. 1999, 121, 734-753.
(37) Dullenkopf, W.; Castro-Palomino, J. C.; Manzoni, L.; Schmidt, R.
R. Carbohydr. Res. 1996, 296, 135-147.
(26) Demchenko, A. V.; Kamat, M. N.; De Meo, C. Synlett 2003, 1287-
1290.
(27) Demchenko, A. V.; Malysheva, N. N.; De Meo, C. Org. Lett. 2003,
5, 455-458.
(28) Demchenko, A. V. Lett. Org. Chem. 2005, 2, 580-589.
(38) Fridman, M.; Solomon, D.; Yogev, S.; Baasov, T. Org. Lett. 2002,
4, 281-283.
J. Org. Chem, Vol. 72, No. 4, 2007 1481

TABLE 1. Synthesis of 1,2-trans-Linked Disaccharides 9-12
yield, %
entry
1
donor
acceptor
promoter
product
a-b-c-d
1-2-3-4
5
MeOTf
AgOTf
MeOTf
AgOTf
MeOTf
AgOTf
MeOTf
AgOTf
9
92-88-89-79a
90-91-93-87a
84-89-78-ndb
86-88-86-nd
87-88-84-nd
85-90-89-nd
92-92-80-nd
90-88-84-nd
2
3
4
1-2-3-4
1-2-3-4
1-2-3-4
6
7
8
10
11
12
a Synthesis of 9d: incomplete reaction (ca. 70% conversion in 16 h); the yield is based on the acceptor recovered. b nd: no data reported; the reaction
was too slow (ca. 20-40% conversion in 24 h) to have practical application.
SCHEME 2
FIGURE 1. Differently N-substituted SBox glycosyl donors.
lective activation of the 2-NPhth-protected glycosyl donor over
the 2-azido acceptor. Unfortunately, only a modest yield of 31%
could be achieved.39 Other representative examples of the
selective activation of derivatives of the 2-deoxy-2-amino series
make use of remote arming or disarming protecting groups40
or the glycosyl donor preactivation concept.41
To explore this opportunity, we obtained a suitable glycosyl
acceptor 13, which was then glycosylated with glycosyl donor
2, as illustrated in Scheme 2. We determined that this coupling
is best accomplished at a reduced temperature (5 °C); under
these reaction conditions, the disaccharide 14 was obtained in
complete â-stereoselectivity and a high yield of 82%. Finally,
to reiterate the potency of SBox 2-aminoglycosides as glycosyl
donors, subsequent AgOTf-promoted glycosidation of disac-
charide 14 with glycosyl acceptor 5 at room temperature gave
trisaccharide 15 in 73% yield and with complete â-selectivity.
In a similar fashion, based on the significant difference in the
glycosylation rates, 2-TFA or 2-acetamido-protected glycosyl
acceptors could also be glycosidated with NTroc glycosyl
donor 2.
cosides can be chemoselectively activated over a 2-NPhth SBox
glycosyl acceptor. Two-step sequential activation leads to the
trans-trans-linked oligosaccharides. This result significantly
differs from the classic Fraser-Reid’s armed-disarmed approach
developed for neutral sugars, according to which a 1,2-cis
linkage is usually introduced first.34,42 It is to be expected that
the strategy developed would also complement Baasov’s ap-
proach based on S-aryl glycosides.38 Since the SBox glycosides
can be selectively activated over the S-alkyl/aryl moiety,26
a
longer oligosaccharide sequence could be obtained by the
application of a combination of chemoselective and selective
activation protocols.
Experimental Section
In summary, we investigated the application of the SBox
glycosyl donors to the stereoselective and high-yielding syn-
thesis of the 1,2-trans glycosides of the 2-amino-2-deoxysugars.
In addition, we discovered that 2-NTroc-protected SBox gly-
Preparation of the SBox Glycosides. Method A. Typical
procedure for the preparation from glycosyl halides: Crown ether
(18-crown-6, 0.2 mmol) and salt (KSBox, 3.0 mmol) were added
to a stirred solution of a glycosyl halide (1.0 mmol) in dry acetone
(10 mL) under argon. The reaction mixture was stirred for 1-16 h
at rt. Upon completion, the mixture was diluted with CH2Cl2 (30
mL) and washed with 1% aq NaOH (15 mL) and water (3 × 10
(39) Hansson, J.; Garegg, P. J.; Oscarson, S. J. Org. Chem. 2001, 66,
6234-6243.
(40) Ritter, T. K.; Mong, K.-K. T.; Liu, H.; Nakatani, T.; Wong, C.-H.
Angew. Chem., Int. Ed. 2003, 42, 4657-4660.
(41) Yamada, T.; Kinjyo, S.; Yoshida, J.; Yamago, S. Chem. Lett. 2005,
34, 1556-1557.
(42) Fraser-Reid, B.; Wu, Z.; Udodong, U. E.; Ottosson, H. J. Org. Chem.
1990, 55, 6068-6070.
1482 J. Org. Chem., Vol. 72, No. 4, 2007

mL). The organic phase was separated, dried over MgSO4, and
concentrated in vacuo. The residue was purified by column
chromatography on silica gel (ethyl acetate-hexane gradient
elution) to afford the corresponding SBox glycoside. Method B.
Typical procedure for the preparation from glycosyl acetates: The
solution of a glycosyl acetate (0.128 mmol), 2-mercaptobenzoxazole
(0.256 mmol), and activated molecular sieves (3 Å, 100 mg) in
CH2Cl2 (1.0 mL) was stirred under argon for 30 min at rt. The
Lewis acid (BF3-OEt2, AlCl3, ZrCl4, or TMSOTf, 0.256 mmol)
was then added dropwise, and the reaction mixture was kept for
45 min at rt. After that, another portion of 2-mercaptobenzoxazole
(0.256 mmol) and Lewis acid (0.256 mmol) were added, and the
reaction mixture was kept for 1.5-16 h at rt. Upon completion,
the mixture was diluted with CH2Cl2 (10 mL), the solid was filtered
off, and the residue was washed with CH2Cl2 (2 × 10 mL). The
combined filtrate (30 mL) was washed with 1% aq NaOH (15 mL)
and water (3 × 10 mL). The organic layer was separated, dried
over MgSO4, and concentrated in vacuo. The residue was purified
by column chromatography on silica gel (ethyl acetate-hexane
gradient elution) to afford the corresponding SBox glycoside.
Benzoxazolyl-3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-1-thio-
â-D-glucopyranoside (1) was obtained by Method B as white
crystals in 85% yield: Rf ) 0.53 (toluene-ethyl acetate, 3/2, v/v);
mp 132-134 °C (ether-hexane); [R]2D5 145 (c ) 1.00, CHCl3);
mp 133-135 °C; 1H NMR δ 1.89, 2.06, 2.07 (3s, 9H, 3 × COCH3),
4.23-4.12 (m, 2H, J5,6a ) 4.6 Hz, J5,6b ) 2.1 Hz, H-6b, H-5), 4.36
(dd, 1H, J6a,6b ) 12.4 Hz, H-6a), 4.68 (dd, 1H, J2,3 ) 10.5 Hz,
H-2), 5.29 (dd, 1H, J4,5 ) 9.7 Hz, H-4), 5.98 (dd, 1H, J3,4 ) 9.6
Hz, H-3), 6.52 (d, 1H, J1,2 ) 10.9 Hz, H-1), 7.86-7.26 (m, 8H,
aromatic); 13C NMR δ 20.6, 20.8, 20.9, 53.6, 62.0, 68.6, 71.5, 76.6,
77.4, 81.3, 110.3, 119.3, 124.1 (×2), 124.7 (×2), 129.2 (×2), 131.6,
134.7, 141.8, 152.1, 160.0, 169.7, 167.4, 170.2, 170.6; HRMS-
FAB [M + H]+ calcd for C27H25N2O10S, 569.1230; found,
569.1219.
113.8, 117.6, 118.7, 125.0, 125.0, 141.2, 152.2, 157.8, 161.8, 169.5,
170.9, 171.8; HRMS-FAB [M + H]+ calcd for C21H22F3N2O9S,
535.0998; found, 535.1000.
Benzoxazolyl-2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-
â-D-glucopyranoside (4) was obtained as white crystals in 70%
yield: Rf ) 0.53 (acetone-toluene, 1/1, v/v); mp 127-129 °C
(ether-hexane); [R]D25 4.3 (c ) 1.0, CHCl3); 1H NMR δ 1.92,
2.02, 2.06, 2.07 (4s, 12H, COCH3), 3.89-3.94 (m, 1H, J5,6a ) 4.8
Hz, J5,6b ) 2.2 Hz, H-5), 4.14 (dd, 1H, J6a,6b ) 12.6 Hz, H-6b),
4.27 (dd, 1H, H-6a), 4.45 (dd, 1H, J2,3 ) 10.0 Hz, H-2), 5.19 (dd,
1H, J4,5 ) 9.6 Hz, H-4), 5.26 (dd, 1H, J3,4 ) 9.7 Hz, H-3), 5.68 (d,
1H, J1,2 ) 10.7 Hz, H-1), 6.02 (d, 1H, NH), 7.27-7.61 (m, 4H,
aromatic); 13C NMR δ 20.8, 20.9 (×2), 23.3, 53.6, 62.1, 68.1, 74.0,
77.4, 85.2, 110.5, 118.8, 124.7, 124.8, 141.6, 152.1, 162.5, 169.4,
170.5, 170.9, 171.6; HRMS-FAB [M
C21H24N2O9SNa, 503.1100; found, 503.1093.
+
H]+ calcd for
Preparation of Di- and Trisaccharides. Method A. Typical
AgOTf-promoted glycosylation procedure (activation of the SBox
glycosides): A mixture the glycosyl donor (0.11 mmol), glycosyl
acceptor (0.10 mmol), and freshly activated molecular sieves (3
Å, 200 mg) in ClCH2CH2Cl (2 mL) was stirred under argon for
1.5 h. Freshly conditioned AgOTf (0.22 mmol) was added, and
the reaction mixture was stirred for 1-2 h at rt. The mixture was
diluted with CH2Cl2, filtered to remove the solids, and the residue
was washed with CH2Cl2. The combined filtrate (30 mL) was
washed with 20% aq NaHCO3 (15 mL) and water (3 × 10 mL).
The organic phase was separated, dried over MgSO4, and concen-
trated in vacuo. The residue was purified by column chromatog-
raphy on silica gel (ethyl acetate-hexane gradient elution) to afford
a di- or an oligosaccharide derivative. Method B. Typical MeOTf-
promoted glycosylation procedure (activation of SBox glyco-
sides): A mixture of the glycosyl donor (0.11 mmol), glycosyl
acceptor (0.10 mmol), and freshly activated molecular sieves (3
Å, 200 mg) in ClCH2CH2Cl (2 mL) was stirred for 2 h under argon.
MeOTf (0.33 mmol) was added, and the reaction mixture was stirred
for 1-2 h at rt. Triethylamine (0.5 mL) was added to neutralize
the reaction, and the mixture was diluted with CH2Cl2 (30 mL),
the solids were filtered off, and the residue was washed with
CH2Cl2. The combined filtrate was washed with water (4 × 10
mL), and then the organic phase was separated, dried over MgSO4,
and concentrated in vacuo. The residue was purified by column
chromatography on silica gel (ethyl acetate-hexane gradient
elution) to yield the corresponding disaccharide.
Benzoxazolyl-3,4,6-tri-O-acetyl-2-deoxy-2-trichloroethoxycar-
bamoyl-1-thio-â-D-glucopyranoside (2) was obtained as a white
amorphous solid in 73% yield: Rf ) 0.55 (toluene-ethyl acetate,
3/2, v/v); [R]2D5 19.3 (c ) 1.00, CHCl3); H NMR δ 1.96, 2.00,
1
2.01 (3s, 9H, 3 × COCH3), 3.86-3.91 (m, 1H, J5,6a ) 4.8 Hz,
H-5), 4.05-4.12 (m, 2H, H-2, H-6b), 4.22 (dd, 1H, J6a,6b ) 12.5
Hz, H-6a), 4.63 (s, 2H, CH2CCl3), 5.12 (dd, 1H, J3,4 ) 9.7 Hz,
H-4), 5.28 (dd, 1H, J2,3 ) 9.8 Hz, H-3), 5.68 (d, 1H, J1,2 ) 10.7
Hz, H-1), 5.69 (d, 1H, NH), 7.20-7.53 (m, 4H, aromatic); 13C NMR
δ 20.8, 20.8, 20.9, 55.9, 62.0, 68.2, 73.5, 74.7, 76.9, 84.8, 95.4,
110.4, 118.9, 124.8, 128.8, 141.5, 152.1, 154.5, 161.9, 169.6, 170.9,
171.1; HRMS-FAB [M + H]+ calcd for C22H24Cl3N2O10S,
613.0217; found, 613.0217.
Acknowledgment. The authors thank the American Heart
Association (AHA0660054Z) and the National Institutes of
General Medical Sciences (GM077170) for financial support
of this research and NSF for grants to purchase the NMR
spectrometer (CHE-9974801) and the mass spectrometer (CHE-
9708640) used in this work. Dr. R. E. K. Winter and Mr. J.
Kramer are thanked for HRMS determinations.
Benzoxazolyl-3,4,6-tri-O-acetyl-2-deoxy-2-trifluoroacetamido-
1-thio-â-D-glucopyranoside (3) was obtained as an off-white
amorphous solid in 70% yield: Rf ) 0.51 (toluene-ethyl acetate,
1
25
1/1, v/v); [R]D 21.3 (c ) 1.0, CHCl3); H NMR δ 2.01, 2.03, 2.09
(3s, 9H, 3 × COCH3), 3.95-4.00 (m, 1H, J5,6a ) 4.9 Hz, J5,6b
)
Supporting Information Available: Extended experimental
data, characterization, and spectral data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
2.2 Hz, H-5), 4.15 (dd, 1H, J6a,6b ) 12.6 Hz, H-6b), 4.27 (dd, 1H,
H-6a), 4.50 (dd, 1H, J2,3 ) 10.2 Hz, H-2), 5.19 (dd, 1H, J4,5 ) 9.8
Hz, H-4), 5.46 (dd, 1H, J3,4 ) 9.8 Hz, H-3), 5.76 (d, 1H, J1,2
)
10.7 Hz, H-1), 7.21-7.56 (m, 4H, aromatic), 7.73 (d, 1H, NH);
13C NMR δ 20.6, 20.8, 20.9, 62.1, 68.0, 73.8, 77.2, 84.0, 110.6,
JO062171D
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