C-5 modified S-benzoxazolyl sialyl donors: Towards more efficient selective sialylations

Article abstract of DOI:10.1002/ejoc.201100539

We previously reported that the selective activation of an S-benzoxazolyl (SBox) sialyl donor over a galactosyl acceptor equipped with a thioethyl anomeric moiety can be performed in high yield but with poor stereoselectivity. To optimize this strategy, w

Full text of DOI:10.1002/ejoc.201100539

FULL PAPER
DOI: 10.1002/ejoc.201100539
C-5 Modified S-Benzoxazolyl Sialyl Donors: Towards More Efficient Selective
Sialylations
Benjamin N. Harris,[a] Payal P. Patel,[a] Chase P. Gobble,[a] Matthew J. Stark,[a] and
Cristina De Meo*[a]
Keywords: Sialylation / Glycosylation / Bismuth / Glycoconjugates
We previously reported that the selective activation of an S-
benzoxazolyl (SBox) sialyl donor over a galactosyl acceptor
equipped with a thioethyl anomeric moiety can be performed
in high yield but with poor stereoselectivity. To optimize this
strategy, which allows the synthesis of complex carbo-
hydrates to be shortened, a range of SBox sialyl donors modi-
fied at C-5 were synthesized and tested. In particular, the
combination of the SBox leaving group and an oxazolidinone
at C-4,5 allowed superior stereocontrol in various solvents
and at different temperatures. Nearly complete stereoselec-
tivity was obtained in the presence of bismuth(III) triflate in
a dichloromethane/tetrahydrofuran (1:1) solvent system.
Introduction
cated by the intrinsic structural features of sialic acid, re-
Sialic acid containing glycoconjugates are natural com- sulting in poor yields and/or stereoselectivities.[3–5] Al-
plex molecules, which are involved in numerous biological though notable progress has been made in this research
phenomena, ranging from cell–cell adhesion and mobility field in the last decade, good yields along with complete
to oncogenesis and recognition by viruses and bacteria.[1,2] control of stereoselectivities for the synthesis of sialosides
Therefore, the synthesis and biomedical investigations of is still a goal to be reached. Perhaps one of the most chal-
sialic acids and bioconjugates thereof is an important tool lenging linkages to be stereocontrolled is the synthesis of
for a better understanding of their biological roles and for α(2–6)-sialosides, which in general can be accomplished in
designing sialotherapeutics. Glycosylations to form anom- high yields but with modest stereoselectivities. On the other
eric linkages of sialic acid (sialylations) are often compli- hand, this type of linkage is very common in glycoconju-
Scheme 1. (a) Selective activation for the synthesis of sialosides; (b) 4,5-oxazolidinone-directed α-sialylation.
gates and therefore is associated with many important bio-
[a] Southern Illinois University Edwardsville,
logical phenomena. For example, hemmaglutinin of the hu-
man influenza A virus can specifically recognize α(2–6)-
linked sialic acid. Previously, we reported that the use of
thioimidoyl leaving groups allows high yields in sialylations
Edwardsville, IL 62026, USA
Fax: +1-618-650-3556
E-mail: cdemeo@siue.edu
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100539.
Eur. J. Org. Chem. 2011, 4023–4027
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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B. N. Harris, P. P. Patel, C. P. Gobble, M. J. Stark, C. De Meo
FULL PAPER
of various galactosyl acceptors to be achieved.[6] In ad-
dition, we demonstrated that sialyl thioimidate donor 1a
can be selectively activated over galactosyl acceptors
equipped with an S-ethyl anomeric moiety (Scheme 1a). Be-
cause the resulting disaccharide is already equipped with
the thioethyl leaving group, it can be glycosidated directly
to obtain larger oligosaccharides without the necessity to
perform the intermediate protecting group manipulations
between the glycosylation steps. This approach has been al-
ready adopted by other research groups.[7,8] For instance,
Hung et al. reported a very efficient one-pot synthesis of a
hemmaglutinin-binding trisaccharide (and its analogs) by
selective activation of donor 1a over an S-tolyl acceptor in
high yields.[8] Unfortunately, only modest stereoselectivities
were observed in sialylations of primary galactosyl ac-
ceptors, and this important drawback stands out as a sig-
nificant limitation in the broadening of the scope of this
promising selective activation concept.
As a part of a parallel investigation, we reported that the
introduction of a C-5 oxazolidinone moiety can dramati-
cally improve the efficiency of sialylation for the synthesis
of α(2–6) linkages, obtaining high yields and stereoselecti-
vity in the presence of various solvents and temperatures
(Scheme 1b).[9,10] Similar observations were concomitantly
reported by the groups of Takahashi and Crich.[11–14] To
adapt both thioimidoyl and the C-5 modification ap-
proaches to chemical sialylation, herein we report a cooper-
ative study of these two concepts. For this purpose we pre-
pared a range of SBox sialyl donors (1b–d, Figure 1) modi-
fied at C-5 and performed a comprehensive study of their
(2–6)-sialidations with diacetone galactose 5 and thioethyl
acceptor 2 under various reaction conditions.
Scheme 2. Synthesis of SBox sialyl donors 1b–d. Reagents and con-
ditions: (a) 1. ICl (1 m in DCM), DCM, 3 Å MS; 2. KSBox, 18-
crown-6, acetone or HSBox, DIPEA, DCM, 62–72%.
In our previous study we reported[6] that the coupling
between SBox sialyl donor 1a and diacetone galactose ac-
ceptor 5 in the presence of N-iodosuccinimide (NIS) and
triflic acid in acetonitrile gives disaccharide 6a with a good
yield of 70% (Table 1, Entry 1). Because relatively low
stereoselectivity was detected (α/β = 1.6:1), we assumed that
these reaction conditions (NIS/TfOH, MeCN) would be a
good starting point for studying the effect of various C-5
protecting groups in new sialyl donors 1b–d. Immediately
itbecameapparentthattheintroductionofanadditionalacet-
yl group resulted in a dramatic increase in the reactivity of
sialyl donor 1b in comparison to that of its monoacetylated
counterpart 1a. Thus, disaccharide 6b was formed nearly
instantaneously and was isolated in 96% yield (Table 1, En-
try 2). This increase in reactivity of N-acetylacetamido-pro-
tected sialic acid derivatives correlates well with the study
of S-methyl sialyl donors by Boons.[15] Unfortunately, the
stereoselectivity of this reaction remained low, and disac-
charide 6b was obtained as a 1.2:1 mixture of α/β-anomers.
A somewhat different effect was observed with 5-triflu-
roacetamido-protected sialyl donor 1c. Whereas no notable
increase in reactivity was detected in comparison to that of
N-acetamido donor 1a, a slightly improved yield of 78%
and a notably higher stereoselectivity (α/β = 5:1) were ob-
served (Table 1, Entry 3). A further improvement in stereo-
selectivity (α/β = 10:1) was achieved in the coupling of C-5
oxazolidinone modified SBox donor 1d. Resulting disacchar-
Table 1. Glycosylation of sialyl donors 1a–d with glycosyl acceptor
5.[a]
Figure 1. SBox sialyl donors 1a–d.
Entry
Donor
Time
[min]
Product
Yield
[%]
Ratio (α/β)
Results and Discussion
1[6]
2
3
1a
1b
1c
1d
960
5
960
60
6a
6b
6c
6d
70
96
78
50
1.6:1
1.2:1
5:1
We found that the synthesis of sialyl donors 1b–d could
be achieved by direct conversion of the respective C-5 modi-
fied thiophenyl donors 4b–d[15–17] in the presence of iodine
chloride followed by treatment with 2-mercaptobenzoxazole
(in the presence of DIPEA) or its potassium salt in the pres-
ence of 18-crown-6 (Scheme 2).
4
10:1
[a] Yields were calculated on anomeric mixtures isolated by size-
exclusion chromatography (LH-20), and the α/β ratio was calcu-
lated by integration of free-standing signals in the H NMR spec-
trum.
1
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C-5 Modified S-Benzoxazolyl Sialyl Donors
ide 6d was isolated in an average yield of 50% (Table 1, nantly as the α-anomer (α/β = 2:1), but with a notable de-
Entry 4).
crease in yield (Table 2, Entry 5). Further improvement in
This initial comparison study supports the general belief stereoselectivity emerged with the application of sialyl do-
that modification at C-5 has a profound effect on the out- nor 1d in dichloromethane at –78 °C. Thus, disaccharide 3d
come of sialylations.[18] The acquired results indicate that was obtained with good stereoselectivity and moderate
diacetyl modification increases the reactivity and yield, yield (α/β = 11:1, 50%; Table 2, Entry 6). The increase in
whereas oxazolidinone modification provides better ste- yield along with a slight decrease in stereoselectivity was
reocontrol of the sialylations. Overall, these results correlate recorded in the presence of a mixture of dichloromethane/
well with our earlier study of sialyl donors equipped with a tetrahydrofuran (1:1) at 0 °C (α/β = 6:1, 74%; Table 2, En-
thiophenyl leaving group, wherein similar trends in yields try 6). By lowering the temperature to –40 °C it was pos-
and stereoselectivities were obtained.[9] Extended experi- sible to reach a higher stereoselectivity (α/β = 15:1, 54%;
mental and direct comparison data are available as a part Table 2, Entry 7).
of the Supporting Information.
This result is an indication that oxazolidinone-protected
As sialyl thioimidates offer a significant advantage over sialyl donor 1d provides superior stereoselectivity for the
conventional thioglycosides by offering the possibility of formation of the α-(2–6) linkage through selective acti-
their selective activation over other leaving groups, further vation. Relatively high yields and/or stereoselectivities have
study emphasized the reaction conditions that would allow also been achieved in several solvent systems at different
for selective activation. For this purpose, we investigated the temperatures when 1d was used as the donor, proving the
selective activation of sialyl donors 1a–d over thioglycoside importance of oxazolidinone protection at C-5 (see the Sup-
acceptor 2. To ensure the selective nature of activation of porting Information).
the SBox leaving group, its activation was performed in the
Further refinement of the reaction conditions required
presence of AgOTf, reaction conditions under which the S- the search for different promoters that could allow even
ethyl moiety remains entirely inert. Previously, we noticed higher yields while maintaining the high stereoselectivity for
that silver triflate promoted reactions are extremely sluggish the coupling of 1d and acceptor 2 (Table 3). Similarly to
in MeCN; therefore, these sialylations were initially per- that reported for acetamido donor 1a,[6] we noticed that the
formed in dichloromethane at –40 °C.[6] Although nearly activation of oxazolidinone-protected donor 1d with Cu-
quantitative yield for the formation of disaccharide 3a was (OTf)2 lead to a notable increase in the reaction time in
achieved, no stereoselectivity preference was detected comparison to AgOTf-promoted activations. Resultantly,
(Table 2, Entry 1). In an attempt to invert the stereoselecti- coupling product 3d was obtained after 3 d in average
vity, we sialidated donor 1c by using tetrahydrofuran/ yields. Nevertheless, good stereoselectivities were main-
dichloromethane, a solvent system that was found advan- tained in tetrahydrofuran used either as a mixture with
tageous for the α-stereoselective sialylation of thioglycos- dichloromethane or neat (Table 3, Entries 1 and 2). Further
ides.[10] Also herein, disaccharide 3c was obtained predomi- improvement emerged with the glycosylation of sialyl donor
1d with acceptor 2 in the presence of bismuth(III) triflate in
dichloromethane/tetrahydrofuran. In this case, the desired
Table 2. Glycosylation of sialyl donors 1a–d with glycosyl acceptor
2.[a]
disaccharide was obtained in an improved yield and with
nearly complete stereoselectivity (66%, α/β = 20:1; Table 3,
Entry 3). These reaction conditions appear optimal for the
Table 3. Glycosylation of sialyl donor 1d under different reaction
conditions.[a]
Entry
Donor
Conditions
Product
Yield
[%]
Ratio (α/β)
1[6]
2
3
4
5
6
7
8
1a
1a
1b
1c
1c
1d
1d
1d
A, –40 °C
3a
3a
3b
3c
3c
3d
3d
3d
98
Ͻ5
76
96
67
50
74
54
1:1
–
1:1.3
1:4
2:1
11:1
6:1
A
A
A
B
A
B
Entry Product Promoter Conditions Time Yield Ratio (α/β)
[min] [%]
1
2
3
4
3d
3d
3d
6d
Cu(OTf)2
Cu(OTf)2
Bi(OTf)3
Bi(OTf)3
A
B
A
A
4320
4320
960
5
57
40
66
92
9:1
13:1
20:1
7:1
B, –40 °C
15:1
[a] Yields were calculated on anomeric mixtures isolated by size-
[a] Yields were calculated on anomeric mixtures isolated by size-
exclusion chromatography (LH-20), and the α/β ratio was calcu-
exclusion chromatography (LH-20), and the α/β ratio was calcu-
1
1
lated by integration of free-standing signals in the H NMR spec-
lated by integration of free-standing signals in the H NMR spec-
trum.
trum.
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B. N. Harris, P. P. Patel, C. P. Gobble, M. J. Stark, C. De Meo
FULL PAPER
solvent (2 mL/0.1 mmol of donor) with activated molecular sieves
(3 Å) overnight under an argon atmosphere. The reaction was pro-
moted the next day with NIS/TfOH (2 equiv./1 equiv. donor) or
AgOTf (2 equiv./1 equiv. donor) or Bi(OTf)3 (3 equiv./1 equiv. do-
nor) or Cu(OTf)2 (3 equiv./1 equiv. donor). The reaction mixture
was stirred until TLC analysis indicated that the reaction had gone
to completion or no further reaction was observed after more than
24 h. The reaction mixture was then diluted with CH2Cl2, filtered
through Celite, and washed with a saturated solution of NaHCO3
[if AgOTf, Cu(OTf)2, or Bi(OTf)3 was used] or NaS2O3 (if NIS/
TfOH was used) and brine. The organic phase was filtered and
concentrated in vacuo. The residue was purified by size-exclusion
column chromatography (Sephadex LH-20; MeOH/CH2Cl2, 1:1) to
afford 3b–d.
formation of the α-(2–6) linkage through selective acti-
vation of the SBox leaving group over thiogalactosyl ac-
ceptor 2 at this stage. An excellent yield and somewhat
lower stereoselectivity was also observed for the coupling
of 1d with acceptor 5 under practically the same reactions
conditions (92%, α/β = 7:1; Table 3, Entry 4). Sialylations
of 1a–c in the presence of Bi(OTf)3 gave similar results to
those shown for silver triflate promoted couplings (see the
Supporting Information for further details).
Conclusions
C-5 modified SBox sialyl donors 1b–d were synthesized
and tested towards traditional and selective glycosylations
under several reaction conditions. The general outcome of
the sialylations was somewhat similar to that previously ob-
served for thiosialyl donors. In fact, an increase in reactivity
was observed for the C-5 modifications as in diacetyl and
trifluoroacetyl when compared to the common acetamido
donor; however, the stereoselectivity of the sialylation reac-
tion was dependent on the reaction conditions. In fact,
Methyl
amido-3,5-dideoxy-2-thio-α-
[Benzoxazol-2-yl-4,7,8,9-tetra-O-acetyl-5-(N-acetyl)acet-
-glycero- -galactonon-2-ulopyranoside]-
D
D
onate (1b): To a solution of 4b[15] (1.7227 g, 2.75 mmol) and acti-
vated 3 Å molecular sieves (2.75 g) in anhydrous CH2Cl2 (27.5 mL)
was added iodine monochloride (1 m in CH2Cl2, 3.0 mL,
3.03 mmol) at 0 °C. The reaction mixture was stirred at 0 °C for
3 h. Upon completion, the reaction mixture was filtered over Celite,
washed with sodium thiosulfate and then brine, concentrated, and
dried in vacuo to afford the chlorinated product. This product was
whereas the use of acetonitrile for the traditional sialyla- immediately dissolved in anhydrous acetone (13.8 mL) and
KSBox[19] (0.572 g, 3.03 mmol) was added followed by 18-crown-
6-ether (0.073 g, 0.275 mmol). The reaction mixture was then
stirred at room temperature under an argon atmosphere for 16 h.
Upon completion, the reaction mixture was evaporated under re-
duced pressure to remove acetone, dissolved in CH2Cl2, washed
with 1% NaOH (1ϫ) and brine (3ϫ), evaporated under reduced
pressure, and concentrated in vacuo. The residue was purified by
tions allowed better α-stereocontrol, selective sialylations
required further tuning of the reaction conditions to obtain
good α-stereoselectivities. Very differently from other C-5
modifications is the behavior of SBox sialyl donor 1d bear-
ing an oxazolidinone moiety at C-4,5. As already noticed
for thiosialyl donors, the presence of the trans-fused ring
system allows better stereocontrol of sialylations. In par-
ticular, in the presence of bismuth(III) triflate it was pos-
sible to improve the stereoselectivity of the selective acti-
column chromatography (5% acetone/toluene) to afford 1b as a
white foam (1.31 g, 72%). Rf = 0.51 (acetone/toluene, 1:4). [α]2D6
=
7.73 (c = 1, CHCl3). Data for 1bα: 1H NMR (CDCl3): δ = 1.96,
vation of the SBox sialyl donor over the thioethyl galactosyl 1.97, 2.01, 2.05 (4 s, 12 H, OCOCH3), 2.30, 2.37 (2 s, 6 H, COCH3),
2.28–2.35 (m, J3ax,3eq = 12.9 Hz, J3ax,4 = 10.7 Hz, 1 H, 3-Hax), 3.12
(dd, J3ax,3eq = 12.9 Hz, J3eq,4 = 5.1 Hz, 1 H, 3-Heq), 3.81 (s, 3 H,
OCH3), 4.15 (dd, J9b,8 = 7.2 Hz, J9b,9a = 12.6 Hz, 1 H, 9b-H), 4.14–
acceptor to nearly complete α-stereoselectivity. This finding
will allow for more efficient selective α(2–6) sialylations and
may provide a new tool for performing high-throughput se-
quential glycosylations in one pot. Further investigations of
other galactosyl acceptors are currently ongoing.
4.24 (m, J5,4 = 10.6 Hz, J5,6 = 10.1 Hz, 1 H, 5-H), 4.33 (dd, J9a,8
=
2.8 Hz, 1 H, 9a-H), 5.03 (dd, J6,7 = 1.7 Hz, 1 H, 6-H), 5.10 (dd,
J7,8 = 7.0 Hz, 1 H, 7-H), 5.20–5.26 (m, 1 H, 8-H), 5.50–5.61 (ddd,
J3ax,4 = 10.7 Hz, 1 H, 4-H), 7.60–7.75 (m, 4 H, aromatic) ppm. 13
C
NMR (CDCl3): δ = 20.7, 20.9, 25.9, 27.9, 29.7, 39.3, 53.7, 56.8,
61.4, 66.9, 67.2, 69.8, 72.8, 76.6, 77.0, 77.4, 86.6, 110.9, 120.1,
124.7, 126.0, 141.6, 152.5, 256.9, 167.5, 169.5, 169.8, 170.1,
170.5 ppm. HR MS (FAB): calcd. for C29H35N2O14S [M + H]+
667.1809; found 667.1803.
Experimental Section
General Synthesis of Sialyl Donors 1b–d: To a solution of 4b–d[15–17]
and activated 3 Å molecular sieves in anhydrous CH2Cl2 was added
at 0 °C iodine monochloride (1 m in CH2Cl2). The reaction mixture
was then stirred at 0 °C for 3 h. Upon completion, the reaction
mixture was diluted with dichloromethane, filtered over Celite,
washed with sodium thiosulfate and then brine, concentrated, and
dried in vacuo to afford the chlorinated product. This product was
immediately dissolved in anhydrous acetone and KSBox[19] was
added with 18-crown-6 ether. Alternatively, the residue was dis-
solved in dry CH2Cl2 and 2-mercaptobenzoxazole (HSBox) was
added followed by the addition of DIPEA; the reaction mixture
was stirred at room temperature under an argon atmosphere for
16 h. Upon completion, the reaction mixture was diluted with
CH2Cl2 and washed with 1% aq. NaOH and then brine, evaporated
under reduced pressure, and concentrated in vacuo. The residue
was purified by column chromatography (5% acetone/toluene) to
afford 1b–d.
Methyl [Benzoxazol-2-yl-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-thio-
5-trifluoroacetamido-α-D-glycero-D-galactonon-2-ulopyranoside]-
onate (1c): To a solution of 4c[16] (777 mg, 1.19 mmol) and activated
3 Å molecular sieves (1.19 g) in anhydrous CH2Cl2 (11.9 mL) was
added iodine monochloride (1 m in CH2Cl2, 1.3 mL, 1.31 mmol) at
0 °C. The reaction mixture was then stirred at 0 °C for 3 h. Upon
completion, the reaction mixture was washed with sodium thiosul-
fate and then brine, concentrated, and dried in vacuo to afford
the chlorinated product. This product was immediately dissolved in
anhydrous CH2Cl2 (5.95 mL) and 2-mercaptobenzoxazole (HSBox,
2.69 mg, 1.78 mmol) was added followed by the addition of DIPEA
(294 μL, 1.78 mmol) dropwise. The reaction mixture was stirred at
room temperature under an argon atmosphere for 16 h. Upon com-
pletion, the reaction mixture was evaporated under reduced pres-
sure and concentrated in vacuo. The residue was purified by col-
umn chromatography (5% ethyl acetate/toluene) to afford 1c as a
General Glycosylation Procedure: A solution of donor 1b–d was
stirred in a 2:1 molar ratio with acceptor 2[20] or 5 in the desired
4026
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Eur. J. Org. Chem. 2011, 4023–4027

C-5 Modified S-Benzoxazolyl Sialyl Donors
white foam (528 mg, 65%). Rf = 0.58 (ethyl acetate/toluene, 2:3).
Supporting Information (see footnote on the first page of this arti-
cle): Selected NMR spectra and full characterization of new com-
pounds.
1
[α]2D6 = 16.1 (c = 0.5, CHCl3). Data for 1cα: H NMR (CDCl3): δ
= 1.94, 1.95, 2.03, 2.05 (4 s, 12 H, OCOCH3), 2.43 (dd, J3ax,3eq
12.9 Hz, J3ax,4 = 11.8 Hz, 1 H, 3-Hax), 2.98 (dd, J3eq,4 = 4.8 Hz, 1
H, 3-Heq), 3.80 (s, 3 H, OCH3), 3.97 (dd, J5,NH = 10.2 Hz, J5,6
=
=
Acknowledgments
10.7 Hz, 1 H, 5-H), 4.16 (dd, J9b,9a = 12.6 Hz, 1 H, 9b-H), 4.33
(dd, J9a,8 = 2.2 Hz, 1 H, 9a-H), 4.41 (dd, J6,7 = 1.8 Hz, 1 H, 6-H),
5.08 (ddd, J4,5 = 10.4 Hz, 1 H, 4-H), 5.21–5.27 (m, 2 H, 7-H, 8-H),
We thank the Research Corporation – Cottrell College Science
6.89 (d, 1 H, NH), 7.33–7.76 (m, 4 H, aromatic) ppm. 13C NMR Award (CC6776) and Southern Illinois University Edwardsville
(CDCl3): δ = 6.3, 20.2, 20.5, 20.6, 20.8, 36.0, 49.8, 53.7, 61.6, 67.2,
68.3, 69.9, 74.4, 76.5, 77.0, 77.4, 86.2, 110.9, 120.1, 124.7, 126.0,
141.5, 167.6, 169.8, 170.2, 170.5, 170.8 ppm. HRMS (FAB): calcd.
for C27H30F3N2O13S [M + H]+ 679.14207; found 679.14203.
Summer Research Fellowship for support.
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[12] H. Tanaka, Y. Nishiura, T. Takahashi, J. Org. Chem. 2009, 74,
4383.
[13] D. Crich, W. Li, J. Org. Chem. 2007, 72, 2387.
[14] D. Crich, W. Li, J. Org. Chem. 2007, 72, 7794.
[15] A. V. Demchenko, G. J. Boons, Tetrahedron Lett. 1998, 39,
3065.
[16] N. E. Byramova, A. B. Tuzikov, N. V. Bovin, Carbohydr. Res.
1992, 237, 161.
[17] K. Benakli, C. Zha, R. J. Kerns, J. Am. Chem. Soc. 2001, 123,
9461.
OCH3), 2.70 (t, J3ax,3eq = 12.4 Hz, 1 H, 3-Hax), 3.09 (t, J5,6
10.0 Hz, J5,NH = 1.6 Hz, 1 H, 5-H), 3.17 (dd, J3eq,4 = 3.8 Hz, 1 H,
3-Heq), 3.79 (s, 3 H, OCH3), 4.01–4.11 (ddd, J3ax,4 = 1.9 Hz, J4,5
=
=
10.8 Hz, 1 H, 4-H), 4.24 (dd, J9b,8 = 3.4 Hz, J9b,9a = 12.8 Hz, 1 H,
9b-H), 4.30 (dd, J9a,8 = 2.2 Hz, 1 H, 9a-H), 4.37 (dd, J6,7 = 1.8 Hz,
1 H, 6-H), 5.04 (dd, J7,8 = 9.2 Hz, 1 H, 7-H), 5.30–5.34 (m, 1 H,
[18] C. De Meo, U. Priyadarshani, Carbohydr. Res. 2008, 343, 1540.
[19] M. N. Kamat, N. P. Rath, A. V. Demchenko, J. Org. Chem.
2007, 72, 6938.
8-H), 5.35 (d, 1 H, H-NH), 7.33–7.75 (m, 4 H, aromatic) ppm. 13
C
NMR (CDCl3): δ = 21.1, 21.3, 21.5, 38.5, 54.5, 58.1, 61.9, 68.5,
69.5, 77.2, 77.7, 78.1, 87.5, 111.6, 120.7, 125.5, 126.5, 142.2, 153.0,
159.4, 168.5, 170.0, 171.1, 172.1 ppm. HRMS (FAB): calcd. for
C24H27N2O12S [M + H]+ 567.12847; found 567.12842.
[20] W. Birberg, H. Lonn, Tetrahedron Lett. 1991, 32, 7453.
Received: April 18, 2011
Published Online: June 8, 2011
Eur. J. Org. Chem. 2011, 4023–4027
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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