On orthogonal and selective activation of glycosyl thioimidates and thioglycosides: Application to oligosaccharide assembly

Article abstract of DOI:10.1021/jo201117s

Discrimination among S-thiazolinyl (STaz), S-benzoxazolyl (SBox), and S-ethyl anomeric leaving groups was achieved by fine-tuning activation conditions. Preferential glycosidation of a certain leaving group is determined neither by the strength of the act

Full text of DOI:10.1021/jo201117s

ARTICLE
pubs.acs.org/joc
On Orthogonal and Selective Activation of Glycosyl Thioimidates and
Thioglycosides: Application to Oligosaccharide Assembly
Sophon Kaeothip and Alexei V. Demchenko*
Department of Chemistry and Biochemistry, University of Missouri—St. Louis, One University Boulevard, St. Louis, Missouri 63121,
United States
S Supporting Information
b
ABSTRACT: Discrimination among S-thiazolinyl (STaz),
S-benzoxazolyl (SBox), and S-ethyl anomeric leaving groups
was achieved by fine-tuning activation conditions. Preferential
glycosidation of a certain leaving group is determined neither by
the strength of the activating reagent nor by the stability of the
leaving group itself; instead, the type of activation plays the key
role. The activation conditions established herein were applied
to a sequential five-step synthesis of a hexasaccharide using
six monosaccharide building blocks equipped with six different
leaving groups.
Scheme 1. Selective Activation-Based Approach to Oligo-
saccharide Synthesis (for orthogonal strategy LGc = LGa)
’ INTRODUCTION
Traditional linear approaches to oligosaccharide assembly
are often cumbersome, and consequently the availability of com-
plex glycostructures remains insufficient to address challenges
of modern glycosciences.1ꢀ3 Recent strategic improvements
have significantly shortened the number of synthetic steps
required for oligosaccharide assembly.4 In principle, the use of
the selective activation concept wherein one leaving group is
activated in the presence of another offers flexible oligosaccharide
sequencing. This approach does not rely on the nature of the
protecting groups, such as the chemoselective armedꢀdisarmed
approach wherein the reactivity of the same leaving group on both
glycosyl donor and acceptor counterparts is adjusted by pro-
tecting groups.5ꢀ8 Instead, it requires a few leaving groups (LGa,
LGb, LGc, etc., Scheme 1) that can be sequentially activated.
Unfortunately, this relatively simple concept is limited to the
number of available leavings groups compatible with the principle
of sequential activation.9 In most cases, only two or at most three
leaving groups can be aligned for selective activation sequences.
In part, this limitation can be addressed by related semiortho-
gonal10,11 and orthogonal12,13 strategies. The only requirement
for the orthogonal approach is a set of two orthogonal leaving
groups (LGc = LGa, Scheme 1) and a pair of compatible
orthogonal activators. Although the orthogonal strategy is an
excellent concept for flexible sequencing of oligosaccharides, its
scope remained narrow. Indeed, only one example involving
orthogonal activation of the S-ethyl and fluoride leaving group
was known for about a decade since its invention in 1994.12,13 To
expand the orthogonal concept to other systems in 2004, we
reported that S-thiazolinyl (STaz) and S-alkyl/aryl glycoside
combination14,15 is a viable alternative of the original orthogonal
concept pioneered by Kanie, Ito, and Ogawa. More recently,
Hotha et al.16 introduced a similar concept using propargyl and
n-pentenyl glycosides as well as orthoesters thereof.
Very unexpectedly, it has been also determined that structu-
rally similar STaz vs S-benzoxazolyl (SBox) leaving groups17 also
represent a viable orthogonal pair. The uniqueness of this
approach is that both leaving groups employed are of essentially
the same class, glycosyl thioimidates. While reactions of both SBox
and STaz glycosyl donors promoted with MeOTf were very
effective, MeI or BnBr were only effective for the STaz glycosyl
donors. This discovery created a basis for the development of the
STaz-SBox orthogonal strategy, but it also signified the gap in our
understanding of the thioimidate activation. From our early
mechanistic study,18,19 we already knew that MeOTf-promoted
activation of the SBox glycosyl donors proceeds via the anomeric
sulfur atom (direct activation). This was confirmed by isolating the
departed S-methylated aglycone MeSBox (Scheme 2a).
To explain the different activation pattern of the STaz glycosyl
donors, we anticipated that their activation proceeds via the nitrogen
atom (remote activation). Indeed, this remote activation of STaz
Received: June 2, 2011
Published: July 28, 2011
r
2011 American Chemical Society
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Scheme 2. Activation of Thioimidates: A Study with SBox
(a)18,19 and STaz (b) Glycosides17
entry 9. Thus, glycosidation of 1 with fluoride acceptor 18
performed in the presence of MeOTf afforded disaccharide 19
in 95% yield.
On the basis of results summarized in Table 1, we conclude
that SBox glycosides are excellent glycosyl donors that can be
selectively activated over a variety of other leaving groups.
Particularly high yields have been achieved with the use of
thioglycosides, O-pentenyl glycosides, and glycosyl fluorides as
glycosyl acceptors. However, the activation of the SBox leaving
group over glycosyl acceptors equipped with a STaz moiety
represents a less efficient pathway toward multistep oligosaccharide
synthesis.
As a continuation of this study, a comprehensive investigation
of glycosyl donors equipped with the STaz leaving group
appealed to us as an attractive venue. Previously, we determined
that thioglycosides 21 and 24 and O-pentenyl glycoside 6
successfully withstand typical reaction conditions required for
the activation of STaz glycosides 20 or 23.15 These results are
depicted in Table 2 (entries 1ꢀ3). As aforementioned, while
SBox glycosides are generally more labile than their STaz
counterparts toward a variety of acidic or basic reagents, the
STaz leaving group can be successfully activated under alkylation
conditions in the presence of either BnBr or MeI. SBox glyco-
sides remain completely inert, and these selective activations
were successfully applied to the building blocks of both the
armed and disarmed series (entries 4 and 5, respectively). The
selective, as opposed to chemoselective, nature of this activation
was ultimately proven by the activation of the disarmed STaz
donor 20 over the “armed” SBox acceptor 27. The resulting
disaccharide 31 was isolated in 79% yield (entry 6). Glycosyla-
tion of secondary glycosyl acceptors 32 and 35 equipped with the
SBox moiety was equally successful, and the corresponding
disaccharides 33 and 36 were obtained in good yields and
complete 1,2-cis stereoselectivity (entries 7 and 8). On the basis
of the results summarized in Tables 1 and 2, we believe that if the
activation of one thioimidoyl leaving group over another is
required, the preferred mode for such activation is the activation
of the STaz glycosyl donor over the SBox glycosyl acceptor rather
than the opposite.
showed marginally slower reactions with a powerful promoter, such as
MeOTf.17 When weak alkylating reagents are used (MeI, BnBr), a
powerful nucleophile is needed to replace the iodine or bromine,
respectively. Evidently, this can be achieved with STaz glycosides that
bear the reactive nitrogen atom, but not with the SBox glycosides,
which can only be activated via the exocyclic sulfur.18,19 The credibility
of this working hypothesis was verified by a series of experiments in
which we isolated the N-benzylated byproduct whose identity was
proven by spectral and X-ray methods (Scheme 2b).17
’ RESULTS AND DISCUSSION
With a better understanding of the mechanistic pathways for
thioimidate activation, we were well positioned to undertake
further studies of the expeditious oligosaccharide assembly via
orthogonal and selective activation concepts. Previously, we
demonstrated that SBox leaving group in glycosyl donors
1 and 4 can be efficiently activated over glycosyl acceptor
2 equipped with an S-alkyl anomeric moiety (Table 1, entries 1
and 2) or O-pentenyl acceptor 6 (entry 3).18,20 These glycosyla-
tions were promoted by AgOTf, which is a very powerful
activator of thioimidates, but is entirely neutral toward thioglyco-
sides or pentenyl glycosides. Resultantly, disaccharides 3, 5, and 7
were obtained in nearly quantitative yields. Activations of SBox
glycosyl donors 8 and 11 over STaz glycosyl acceptors 9 and 12
in the presence of Cu(OTf)2 were also previously reported
(entries 4 and 5).15 Although the synthesis of 10 and 13 was
successful, our subsequent in-depth study indicated that the
additional reinforcement of the protecting groups was essential
for these couplings. Indeed, in both reactions armed glycosyl
donors and disarmed glycosyl acceptors are employed.
Further studies revealed that indeed SBox can be activated
over the STaz group independently of the protecting groups in
the presence of Bi(OTf)3 (entry 6).17 This finding created the
basis for the development of the thioimidate-only orthogonal
strategy for oligosaccharide synthesis because also STaz glyco-
sides can be activated over the SBox moiety under alkylation
conditions (vide supra). However, only relatively modest yields
in the 70% yield range could be generally obtained in the
presence of Bi(OTf)3. Our further efforts to improve this result
did not result in the improved yields. The investigation of
secondary glycosyl acceptors 9 and 16 (entries 7 and 8) provided
a similar glycosylation outcome to that of the primary acceptor
12. Continuing the search of other suitable selective activations,
we found that the SBox leaving group can be reliably activated
over glycosyl fluorides, and a representative example is shown in
Additionally, the investigation of thioglycosides as glycosyl
donors in selective activations seemed attractive because in all
previous examples, thioglycosides were used as glycosyl accep-
tors. Many reliable reaction conditions for the glycosidation
of thioglycosides have been developed,21 and some were found
compatible with selective activations. For example, NIS/
AgOTf-promoted activation of thioglycosides created a basis
for the first example of orthogonal activation over glycosyl
fluorides.12
MeOTf-promoted activation of thioglycosides22 allows for a
very selective activation over O-pentenyl glycosides (Table 3,
entries 1 and 2), which created a basis for the semiorthogonal
strategy for oligosaccharide synthesis.10 Thioglycosides (both
S-alkyl and S-aryl) can be also activated over STaz glycosides, and
this can be accomplished in the presence of NIS and TfOH
(entries 3 and 4).14,15 The use of catalytic TfOH is necessary
because a stoichiometric amount of TfOH would also trigger the
activation of the STaz leaving group. Although SEt and STaz
leaving groups can be reliably differentiated at the monosaccharide
level, it represents a particular difficulty at the advanced stage of
the assembly when oligosaccharide donor is used. Thus, we
noticed that the efficiency of the orthogonal activation of STaz vs
SEt drops at the stage of tetra- and pentasaccharides.15 Typically,
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Table 1. Activation of SBox Glycosyl Donors over Glycosyl Acceptors Bearing SEt, O-Pentenyl, STaz, or F Leaving Groups
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oligosaccharide donor is much less reactive than its respective
monosaccharide counterpart, and if additional amounts of TfOH
are required to ensure the completion of activation of the S-ethyl
donor, this can pose a problem for the acceptor equipped with
the STaz moiety that may be also activated in this enhanced
acidic environment.
Therefore, further search of promoters suitable for more
selective activation of thioglycosides over STaz glycosides
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Table 2. Activation of STaz Glycosyl Donors over Glycosyl Acceptors Bearing SEt, SPh, O-Pentenyl, or SBox Leaving Groups
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appealed to us as a useful expansion of this study. Herein, we
report that dimethyl(methylthio)sulfonium trifluoromethane-
sulfonate (DMTST)23 is unable to activate the STaz leaving
group, whereas it is a well-known activator for thioglycosides.24
This allowed us to perform reliable activations of various
thioglycosides over a broad range of STaz acceptors (entries
5ꢀ10, Table 3). We believe that the differential nature of
activation of the SEt and STaz moieties is due to the modes by
which these two leaving groups are activated: direct for S-alkyl
glycosides25 and remote for STaz glycosides.17 Herein the
formation of the anomeric sulfonium ion in case of thio-
glycosides25 is a more likely pathway than the formation of the
NꢀS bond, as it would have to be the case with the STaz
glycosides. The yields obtained here are in line with yields
obtained in DMTST activations of thioglycosides that typically
do not exceed the 80% range. Therefore, these results do not
support the selective nature of this activation that is actually very
efficient, as no activation of the STaz leaving group was noticed.
At this point, these results were deemed suitable for performing
selective activations with oligosaccharide building blocks. We
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Table 3. Activation of SEt Glycosyl Donors over Glycosyl Acceptors Bearing O-Pentenyl, STaz, or SBox Leaving Groups
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Scheme 3. Synthesis of Hexasaccharide 55 via the Five-Step Sequential Activation Strategy
believe that a further search of suitable promoters to differentiate
the reactivity of STaz and SEt leaving groups may help to
improve the outcome of these selective couplings. In this context,
we noticed that the differentiation between thioglycosides and
SBox glycosides can be also achieved in the presence of DMTST
(entry 11). However, the efficiency of this selective activation is
significantly lower than that of SEt over STaz, because the SBox
moiety is activated via the anomeric sulfur, a typical pathway for
the activation of S-ethyl glycosides.
AgClO4 and Cp2ZrCl2, and the resulting pentasaccharide 53 was
isolated in 84% yield. Finally, thioglycoside 53 was activated over
O-pentenyl glycosyl acceptor 54 in the presence of MeOTf. The
resulting hexasaccharide 55 was isolated in 72% yield.
It is noteworthy that the use of the O-pentenyl moiety at this
last stage represents an important practical aspect of oligosac-
charide synthesis. On one hand, O-pentenyl can be glycosidated
to elongate the sequence further or it can be easily hydrolyzed if
the complete deprotection is required. On another hand,
O-pentenyl glycoside represents a conjugation-amendable linker
that can be either used in thiolꢀene conjugation32 or converted
into thiol,33 aldehyde,34,35 or carboxylic acid and to effect other
common conjugation techniques.36ꢀ38
With the study of a variety of selective activations summarized
in Tables 1-3, we decided to undertake multistep sequential
selective activations. As a possible LGa for the first stage activa-
tion, we were initially considering the most common highly
reactive glycosyl donors: glycosyl bromides and trichloroaceti-
midates. In our hands, however, their activation over the STaz
leaving group was somewhat inconsistent.15 With the reinvesti-
gation of glycosyl thiocyanates, reactive glycosyl donors intro-
duced by Kochetkov,26ꢀ28 we determined that their activation can
be reliably achieved with Cu(OTf)2, reaction conditions under
which the STaz group reacts sluggishly.29 Indeed, Cu(OTf)2-
promoted activation of thiocyanate donor 50 over STaz glycosyl
acceptor 12 was very efficient, and the resulting disaccharide
14 was isolated in 89% yield (Scheme 3). The STaz moiety of
disaccharide 14 was then activated over SBox glycosyl acceptor
29 under alkylation conditions to afford the corresponding
trisaccharide 51 in 67% yield. Subsequently, the SBox leaving
group of 51 was activated over glycosyl fluoride acceptor 18 in
the presence of MeOTf. This selective activation resulted in the
formation of tetrasaccharide 52 in 87% yield. The activation of
glycosyl fluorides over thioglycosides is a well-established pro-
tocol, dating back to Nicolaou’s study of the two-step activation
strategy for oligosaccharide synthesis.30,31 Herein, a protocol
used in the original Ogawa orthogonal strategy was adopted.12
Thus, activation of glycosyl fluoride tetrasaccharide 52 over
thioglycosides acceptor 21 was performed in the presence of
’ CONCLUSIONS
We presented a thorough study of the selective activation of
differentleavinggroups that allowed us to align six different leaving
groups to perform a five-step synthesis of a linear hexasaccharide
from six monosaccharide building blocks. It is to be expected that
the same or similar sequential activation would be suitable for the
synthesis of other oligosaccharide sequences including those of
high biological significance and/or therapeutic relevance.
’ EXPERIMENTAL SECTION
General. Column chromatography was performed on silica gel 60
(70ꢀ230 mesh), and reactions were monitored by TLC on Kieselgel 60
F254. 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 <40 °C. Dichloromethane and 1,2-dichlor-
oethane were distilled from CaH2 directly prior to application. Methanol
was dried by refluxing with magnesium methoxide, distilled, and stored
under argon. Pyridine was dried by refluxing with CaH2 and then
distilled and stored over molecular sieves (3 Å). Molecular sieves
(3 Å and 4 Å), used for reactions, were crushed and activated in vacuo
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at 390 °C during 8 h in the first instance and then for 2ꢀ3 h at 390 °C
directly prior to application. AgOTf was coevaporated with toluene (3 ꢁ
10 mL) and dried in vacuo for 2ꢀ3 h directly prior to application.
DMTST was prepared in accordance to previously reported methods.
1H NMR spectra were recorded at 300 and 500 MHz, and 13C NMR
spectra were recorded at 75 and 125 MHz.
1.27 mmol). Analytical data for 34: Rf = 0.41 (ethyl acetate/hexane, 4/6,
v/v); [R]22D = +16.6° (c = 1, CHCl3); 1H NMR: δ, 3.32 (dd, 2H, JCH2S,
CH2N = 8.32 Hz, CH2S), 3.61ꢀ3.71 (m, 4H, H-3, 4, 6a, 6b), 3.92 (dd,
1H, J2,3 = 9.5 Hz, H-2), 4.00 (dd, 1H, J4,5 = 2.3 Hz), 4.10ꢀ4.24 (m, 2H,
CH2N), 4.39ꢀ4.50 (dd, 2H, J = 11.8 Hz, CH2Ph), 4.62 (d, 1H, 2J = 11.6
Hz, 1/2 CH2Ph), 4.69 ꢀ4.85 (m, 2H, CH2Ph), 4.95 (d, 1H, 2J = 11.58
Hz, 1/2 CH2Ph), 5.31 (d, 1H, J1,2 = 9.96 Hz, H-1), 7.27ꢀ7.34 (m, 20H,
aromatic) ppm; 13C NMR: δ, 35.2, 64.4, 68.5, 72.9, 73.6, 73.7, 74.9, 75.9,
77.8, 84.2, 85.3, 127.7 (ꢁ3), 127.8, 127.9, 128.1 (ꢁ2), 128.2 (ꢁ2),
128.4 (ꢁ3), 128.4 (ꢁ2), 128.5 (ꢁ5), 128.6 (ꢁ2), 138.0, 138.1, 138.3,
138.7, 164.2 ppm; HR-FAB MS [M + Na]+ calcd for C37H39NO5S2Na
664.2167, found 664.2164.
2-Thiazolinyl 2-O-Benzyl-4,6-O-benzylidene-1-thio-β-D-
galactopyranoside (16). A solution of ethyl 3-O-acetyl-2-O-ben-
zyl-4,6-O-benzylidene-1-thio-β-D-galactopyranoside39 (0.48 g, 1.08 mmol)
and activated molecular sieves (3 Å, 0.54 g) in CH2Cl2 (16 mL) was
stirred under argon for 1 h. A freshly prepared solution of Br2 in CH2Cl2
(10 mL, 1/165, v/v) was then added, and the reaction mixture was kept
for 10 min at rt. Next, the solid was filtered, and the filtrate was
concentrated in vacuo at rt and dried. The crude residue was then
treated with NaSTaz (2.16 mmol) and 15-crown-5 (0.21 mmol) in dry
acetonitrile (5 mL) under argon for 6 h at rt. Upon completion, the
mixture was diluted with dichloromethane, the solid was filtered, and the
residue was washed with dichloromethane (10 mL). The combined
filtrate was washed with 1% aq NaOH (1 ꢁ 15 mL) and water (2 ꢁ
15 mL). The organic layer was separated, dried with MgSO4, and
concentrated in vacuo. The residue was purified by silica gel column
chromatography to afford 2-thiazolinyl 3-O-acetyl-2-O-benzyl-4,6-O-
benzylidene-1-thio-β-D-galactopyranoside as a white foam in 80% yield
(0.44 g, 0.87 mmol). Selected analytical data: Rf = 0.62 (ethyl acetate/
2-Benzoxazolyl 2-O-Benzyl-4,6-O-benzylidene-1-thio-β-
D-galactopyranoside (35). A solution of ethyl 3-O-acetyl-2-O-
benzyl-4,6-O-benzylidene-1-thio-β-D-galactopyranoside39 (0.4 g, 0.90
mmol) and activated molecular sieves (3 Å, 0.45 g) in CH2Cl2
(14 mL) was stirred under argon for 1 h. A freshly prepared solution
of Br2 in CH2Cl2 (9 mL, 1/165, v/v) was then added, and the reaction
mixture was kept for 10 min at rt. Next, the solid was filtered, and the
filtrate was concentrated in vacuo at rt and dried. Crude residue was then
treated with KSBox (1.8 mmol) and 18-crown-6 (0.18 mmol) in dry
acetone (5 mL) under argon for 6 h at rt. Upon completion, the mixture
was diluted with dichloromethane (10 mL), the solid was filtered, and
the residue was washed with dichloromethane (5 mL). The combined
filtrate was washed with 1% aq NaOH (1 ꢁ 15 mL) and water (2 ꢁ
15 mL). The organic layer was separated, dried with MgSO4, and con-
centrated in vacuo. The residue was purified by silica gel column
chromatography to afford 2-benzoxazolyl 3-O-acetyl-2-O-benzyl-4,6-
O-benzylidene-1-thio-β-D-galactopyranoside as a colorless foam in
78% yield (0.375 g, 0.70 mmol). Selected analytical data: Rf = 0.75
(ethyl acetate/hexane, 7/3, v/v); 1H NMR: δ, 2.07 (s, 1H, CO2CH3),
3.76 (m. 1H, H-5), 4.03 (dd, 1H, J6a,6b = 12.6 Hz, H-6b), 4.25 (dd, 1H,
J2,3 = 9.7 Hz, H-2), 4.34 (dd, 1H, J6a,6b = 12.7 Hz, H-6a), 4.50 (dd, 1H,
J4,5 = 2.9 Hz, H-4), 4.72 (d, 1H, 2J = 10.92 Hz, 1/2 CH2Ph), 4.87 (d, 1H,
2J = 11.6 Hz, 1/2 CH2Ph), 5.07 (ddd, 1H, J = 3.47, 6.14, 9.63 Hz, H-3),
5.51, (s, 1H, >CHPh), 5.58 (d, 1H, J1,2 = 9.9 Hz, H-1), 7.27ꢀ7.48 (m,
14H, aromatic) ppm. 2-Benzoxazolyl 3-O-acetyl-2-O-benzyl-4,6-O-ben-
zylidene-1-thio-β-D-galactopyranoside was dissolved in methanol
(5 mL) containing 1 M NaOCH3, and the resulting mixture was stirred
for 1 h at rt. Dowex (H+) was added until neutral pH, and the resin was
filtered and washed successively with methanol. The combined filtrate
was concentrated in vacuo. The residue was purified by silica gel column
chromatography to obtain the title compound as a white solid in 70%
yield (0.25 g, 0.50 mmol). Analytical data for 35: Rf = 0.44 (ethyl
acetate/hexane, 7/3, v/v); [R]21D = ꢀ67.1° (c = 1, CHCl3); 1H NMR:
δ, 2.67 (d, 1H, J = 8.4 Hz, OH), 3.73 (m, 1H, H-5), 3.93 ꢀ3.98 (m, 2H,
H-2, 3), 4.05 (dd, 1H, J6a,6b = 12.7 Hz, H-6a), 4.31ꢀ4.38 (m, 2H, H-4,
6b), 4.88 (dd, 2H, J = 10.81 Hz, CH2Ph), 5.14 (d, 1H, J1,2 = 9.7 Hz, H-1),
5.57 (s, 1H, >CHPh), 7.24ꢀ7.80 (m, 14H, aromatic) ppm; 13C NMR:
δ, 60.1, 70.5, 74.5, 75.7, 75.9, 78.1, 84.8, 101.5, 110.2, 119.0, 124.4, 124.5,
124.6, 126.6 (ꢁ2), 128.0, 128.3 (ꢁ2), 128.4, 128.5 (ꢁ2), 129.5, 137.6,
137.9, 141.8, 151.9, 162.1 ppm; HR-FAB MS [M + Na]+ calcd for
C27H25NO6SNa 514.1300, found 514.1295.
1
hexane, 7/3, v/v); H NMR: δ, 2.05 (s, 3H, COOCH3), 3.37 (t, 2H,
CH2S), 3.63 (m, 1H, H-5), 4.00ꢀ4.05 (m, 2H, J2,3 = 9.7 Hz, H-2, 4),
4.17, 4.28 (m, 2H, CH2N), 4.36 (dd, 1H, J6a,6b = 11.3 Hz, H-6b), 4.55
(dd, 1H, J5,6a = 3.5 Hz, H-6a), 4.65 (d, 1H, 2J = 10.9 Hz, 1/2 CH2Ph),
4.83 (d, 1H, 2J = 10.9 Hz, 1/2 CH2Ph), 5.00 (dd, 1H, J3,4 = 3.5 Hz, H-3),
5.43 (d, 1H, J1,2 = 9.9 Hz, H-1), 5.50 (s, 1H, >CHPh), 7.26ꢀ7.54 (m,
10H, aromatic) ppm. 2-Thiazolinyl 3-O-acetyl-2-O-benzyl-4,6-O-ben-
zylidene-1-thio-β-D-galactopyranoside was dissolved in methanol
(5 mL) containing 1 M NaOCH3, and the resulting mixture was stirred
for 1 h at rt. Dowex (H+) was added until neutral pH, and the resin was
filtered off and washed successively with methanol. The combined
filtrate was concentrated in vacuo, and the residue was purified by silica
gel column chromatography to afford the title compound as a white solid
in 75% yield (0.30 g, 0.65 mmol). Analytical data for 16: Rf = 0.40 (ethyl
acetate); [R]25D = ꢀ15.3° (c = 1, CHCl3); 1H NMR: δ, 2.61 (s, 1H, J =
8.0 Hz), 3.69 (dd, 2H, JCH2S,CH2N = 8.3 Hz, CH2S), 3.61 (m, 1H, H-5),
3.74 (dd, 1H, J2,3 = 9.6 Hz, H-2), 3.85 (m, 1H, H-3), 4.03 (dd, 1H, J6a,6b
=
12.6 Hz, H-6a), 4.11ꢀ4.31 (m, 3H, H-4, CH2N), 4.38 (dd, 1H, H-6b),
4.83 (dd, 2H, J = 11.1 Hz, CH2Ph), 5.34 (d, 1H, J1,2 = 9.8 Hz, H-1), 5.56
(s, 1H, >CHPh), 7.26ꢀ7.52 (m, 10 H, aromatic) ppm. 13C NMR: δ,
35.3, 64.4, 69.2, 70.4, 74.6, 75.8, 75.9, 78.3, 84.5, 101.6, 126.7 (ꢁ2),
128.1, 128.4 (ꢁ4), 128.6 (ꢁ2), 129.5, 137.7, 138.0, 163.9 ppm; HR-
FAB MS [M + Na]+ calcd for C23H25NO5S2Na 482.1072, found
482.1080.
2-Thiazolinyl 2,3,4,6-Tetra-O-benzyl-1-thio-β-D-galacto-
pyranoside (34). The solution of ethyl 2,3,4,6-O-benzyl-1-thio-β-D-
galactopyranoside (46)40 (1.0 g, 1.71 mmol) and activated molecular
sieves (3 Å, 0.85 g) in CH2Cl2 (25 mL) was stirred under argon for 1 h.
Freshly prepared solution of Br2 in CH2Cl2 (16 mL, 1/165, v/v) was
then added, and the reaction mixture was kept for 5 min at rt. Next, the
solid was filtered, and the filtrate was concentrated in vacuo at rt. The
crude residue was then treated with NaSTaz (3.4 mmol) and 15-crown-5
(0.34 mmol) in dry acetonitrile (10 mL) under argon for 6 h at rt. Upon
completion, the mixture was diluted with dichloromethane (20 mL), the
solid was filtered, and the residue was washed with dichloromethane
(10 mL). The combined filtrate was washed with 1% aq NaOH (1 ꢁ
20 mL) and water (2 ꢁ 20 mL). The organic layer was separated, dried
with MgSO4, and concentrated in vacuo. The residue was purified
by silica gel column chromatography (ethyl acetateꢀtoluene gradient
elution) to afford the title compound as a white solid in 75% (0.82 g,
General Glycosylation Procedures. method A: Cu(OTf)2-Pro-
moted Glycosylation. A mixture the glycosyl donor (0.11 mmol),
glycosyl acceptor (0.10 mmol), and freshly activated molecular sieves
(4 Å, 200 mg) in (ClCH2)2 (2 mL) was stirred under argon for 1 h at rt.
Cu(OTf)2 (0.13ꢀ0.22 mmol) was added, and the reaction mixture was
stirred for 3ꢀ5 h at rt. Upon completion, the reaction mixture was
diluted with CH2Cl2, the solid was filtered, 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 concentrated in vacuo.
The residue was purified by column chromatography on silica gel
7394
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The Journal of Organic Chemistry
ARTICLE
(ethyl acetate/hexane gradient elution) to afford a di- or oligosaccharide
derivative. Anomeric ratios (if applicable) were determined by compar-
ison of the integral intensities of relevant signals in 1H NMR spectra.
Method B: A Typical Bi(OTf)3-Promoted Glycosylation Procedure. A
mixture the glycosyl donor (0.11 mmol), glycosyl acceptor (0.10 mmol),
and freshly activated molecular sieves (3 Å, 200 mg) in (ClCH2)2
(2 mL) was stirred under argon for 1 h at rt. The reaction mixture was
cooled to 0 °C, and then Bi(OTf)3 (0.22 mmol) was added. Next, the
reaction mixture was allowed to warm and was stirred for an additional
1ꢀ2 h at rt. Upon completion, the reaction mixture was diluted with
CH2Cl2, the solid was filtered, 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 concentrated in vacuo. The residue was purified by
column chromatography on silica gel (ethyl acetate/hexane gradient
elution) to afford a di- or oligosaccharide derivative. Anomeric ratios
(if applicable) were determined by comparison of the integral intensities
of relevant signals in 1H NMR spectra.
Cp2ZrCl2 (0.22 mmol) were then added, and the reaction mixture was
stirred for 3ꢀ5 h at rt. Upon completion, the reaction mixture was
diluted with CH2Cl2, the solid was filtered, 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 concentrated in vacuo. The residue
was purified by column chromatography on silica gel (ethyl acetate/
hexane gradient elution) to afford a di- or oligosaccharide derivative.
Anomeric ratios (if applicable) were determined by comparison of the
integral intensities of relevant signals in 1H NMR spectra.
2-Thiazolinyl 2,3,4-Tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-benzoyl-
β-D-glucopyranosyl)-1-thio-β-D-glucopyranoside (14). The
title compound was obtained by method B from benzoxazolyl 2,3,4,6-
tetra-O-benzoyl-1-thio-β-D-glucopyranoside (1)19 and 2-thiazolinyl
2,3,4-tri-O-benzoyl-1-thio-β-D-glucopyranoside (12)15 in 69% yield
as a white foam. The title compound was also obtained by method A
from 2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl thiocyanate (50)41
and 12 in 89%. Analytical data for 14 was in a good agreement with
those reported previously.42
Method C: MeOTf-Promoted Glycosylation Procedure. A mixture the
glycosyl donor (0.11 mmol), glycosyl acceptor (0.10 mmol), and freshly
activated molecular sieves (3 Å, 200 mg) in (ClCH2)2 (2 mL) was stirred
under argon for 1 h at rt. MeOTf (0.33 mmol) was added, and the
reaction mixture was stirred for 3ꢀ5 h at rt. Upon completion, the
reaction mixture was diluted with CH2Cl2, the solid was filtered, 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 concentrated in
vacuo. The residue was purified by column chromatography on silica gel
(ethyl acetate/hexane gradient elution) to afford a di- or oligosaccharide
derivative. Anomeric ratios (if applicable) were determined by compar-
ison of the integral intensities of relevant signals in 1H NMR spectra.
Method D: Typical BnBr-Promoted Glycosylation Procedure. A
mixture of the glycosyl donor (0.11 mmol), glycosyl acceptor (0.10
mmol), and freshly activated molecular sieves (3 Å, 200 mg) in
(ClCH2)2 (2 mL) was stirred under argon for 1 h. BnBr (0.33ꢀ0.99
mol) was added, and the reaction mixture was stirred for 24ꢀ36 h at
55 °C. Upon completion, the reaction mixture was diluted with CH2Cl2,
the solid was filtered, and the residue was washed with CH2Cl2. The
combined filtrate (30 mL) was washed with 20% aq NaHCO3 (10 mL)
and water (3 ꢁ 10 mL), and the organic phase was separated, dried with
MgSO4 and concentrated in vacuo. The residue was purified by column
chromatography on silica gel (ethyl acetate/hexane gradient elution) to
allow the corresponding disaccharide. Anomeric ratios (if applicable)
were determined by comparison of the integral intensities of relevant
signals in 1H NMR spectra.
Method E: DMTST-Promoted Glycosylation Procedure. A mixture of
glycosyl donor (0.11 mmol), glycosyl acceptor (0.10 mmol), and freshly
activated molecular sieves (4 Å, 200 mg) in (ClCH2)2 (2 mL) was stirred
under argon for 1 h at rt. The reaction mixture was cooled to 0 °C, and
then DMTST (0.033 mmol) was added. Next, the reaction mixture was
allowed to warm and was stirred for additional 4ꢀ6 h at rt. Upon
completion, the reaction mixture was quenched with triethylamine
(1 drop), the solid was filtered, the filtrate was diluted with CH2Cl2
(30 mL) and washed with 1% NaOH (15 mL) and water (3 ꢁ 10 mL).
The organic layer was separated, dried with MgSO4, filtered, and
concentrated in vacuo. The residue was purified by column chromatog-
raphy on silica gel (ethyl acetateꢀtoluene gradient elution) to obtain the
corresponding disaccharide. Anomeric ratios (if applicable) were deter-
mined by comparison of the integral intensities of relevant signals in 1H
NMR spectra.
2-Thiazolinyl 2-O-Benzyl-3-O-(2,3,4,6-O-tetrabenzyl-R/β-
D-glucopyranosyl)-4,6-O-benzylidene-1-thio-β-D-glucopyr-
anoside (15). This compound was obtained by method A from 2-
benzoxazolyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranoside (11)43 and
2-thiazolinyl 2-O-benzyl-4,6-O-benzylidene-1-thio-β-D-glucopyrano-
side (9)14 in 71% yield (R/β, 2.4/1) as a white foam. In addition, the
title compound was also obtained method E from ethyl 2,3,4,6-tetra-O-
benzyl-1-thio-β-D-glucopyranoside (40)40 and 2-thiazolinyl 2-O-benzyl-
4,6-O-benzylidene-1-thio-β-D-glucopyranoside (9)14 in 77% yield (R/β
= >25/1). Analytical data for compound 15 was in a good agreement
with those reported previously.14
2-Thiazolinyl 2-O-Benzyl-3-O-(2,3,4,6-tetra-O-benzyl-R-D-
galactopyranosyl)-4,6-O-benzylidene-1-thio-β-D-galacto-
pyranoside (17). This compound was obtained by method A from 2-
benzoxazolyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-galactopyranoside (8)44
and 2-thiazolinyl 2-O-benzyl-4,6-O-benzylidene-thio-β-D-galactopyra-
noside (16) in 52% yield (R/β = >25/1). In addition, this compound
was also achieved by method E from ethyl 2,3,4,6-tetra-O-benzyl-1-thio-
β-D-galactopyranoside (46)40 and 16 in 74% yield (R/β, 15/1) as a
white syrup. Analytical data for 17: Rf = 0.55 (ethyl acetate/toluene, 3/7,
v/v); [R]25D = +48.5° (c = 1, CHCl3); 1H NMR: δ, 3.31ꢀ3.39 (m, 4H,
H-6a0, 6b0, CH2S), 3.55 (dd, 1H, J4 ,5 = 9.7 Hz, J5 ,6a = 3.0 Hz, H-50),
3.73 (m, 1H, J5,6a = 2.0 Hz, H-5), 3.87ꢀ4.39 (m, 14H, 2 ꢁ CH2Ph,
0
0
0
0
CH2N, H-2, 3, 4, 6a, 6b, 20, 30, 40), 4.50ꢀ4.97 (m, 6H, 3 ꢁ CH2Ph), 5.30
0
0
0
(d, 1H, J1 ,2 = 3.7 Hz, H-1 ), 5.34 (d, 1H, J1,2 = 9.7 Hz, H-1), 5.48 (s, 1H,
>CHPh), 7.08ꢀ7.60 (m, 30H, aromatic) ppm; 13C NMR: δ, 35.2, 64.4,
69.2, 69.5, 69.7, 70.1, 72.0, 72.1, 73.1, 73.2, 74.9, 75.2, 75.6, 75.7, 76.2,
76.5, 76.7, 78.7, 84.9, 93.02, 101.5, 126.7 (ꢁ2), 127.5, 127.6 (ꢁ2), 127.7
(ꢁ2), 127.7 (ꢁ4), 127.8, 127.9 (ꢁ2), 128.3 (ꢁ3), 128.4 (ꢁ7), 128.5
(ꢁ4), 129.2, 137.9, 138.2, 138.4, 138.7 (ꢁ2), 138.9, 164.1 ppm; HR-
FAB MS [M + Na]+ calcd for C57H59NO10S2Na 1004.3478, found
1004.3475.
2,3,4-Tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-benzoyl-β-D-
glucopyranosyl)-βꢀD-glucopyranosyl Fluoride (19). The title
compound was obtained by method C from 2-benzoxazolyl 2,3,4,6-
tetra-O-benzoyl-1-thio-β-D-glucopyranoside (1)19 and 2,3,4-tri-O-ben-
zoyl-β-D-glucopyranosyl fluoride (18)45 in 95% yield as a white foam.
Analytical data for 19: Rf = 0.51 (ethyl acetate/toluene, 1/9, v/v);
1
[R]23 = +19.3° (c = 1, CHCl3); H NMR: δ, 3.97 (dd, 1H, J5 ,6a
=
0
0
D
0
0
0
0
0
4.1 Hz, J6a ,6b = 8.2 Hz, H-6a ), 4.15 (m, 3H, H-5, 5 , 6b ), 4.47 (dd, 1H,
J5,6a = 7.2 Hz, J6a,6b = 10.2 Hz, H-6a), 4.63 (dd, 1H, J5,6b = 3.0 Hz, J6a,6b
=
0
0
0
12.2 Hz, H-6b), 5.04 (d, 1H, J1 ,2 = 7.8 Hz, H-1 ), 5.29 (d, 1H, J1,2 = 5.9
Method F: AgClO4/Cp2ZrCl2-Promoted Glycosylation Procedure. A
mixture the glycosyl donor (0.11 mmol), glycosyl acceptor (0.10 mmol),
and freshly activated molecular sieves (4 Å, 200 mg) in (ClCH2)2
(2 mL) was stirred under argon for 1 h at rt. AgClO4 (0.22 mmol) and
0
0
0
Hz, H-1), 5.45ꢀ5.50 (m, 2H, H-2, 4), 5.56 (dd, 1H, J2 ,3 = 7.8 Hz, H-2 ),
0
0
0
5.68 (dd, 1H, J4 ,5 = 9.7 Hz, H-4 ), 5.74 (dd, 1H, J3,4 = 8.5 Hz, H-3), 5.94
(dd, 1H, J3 ,4 = 9.7 Hz, H-30), 7.18ꢀ7.95 (m, 35H, aromatic) ppm;
0
0
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The Journal of Organic Chemistry
ARTICLE
13C NMR: δ, 62.1, 67.6, 68.2, 68.7, 70.4, 70.5 (ꢁ2), 70.7, 70.9, 71.5,
71.9, 73.5, 101.1, 104.7, 107.2, 124.5 (ꢁ2), 127.4 (ꢁ4), 127.5 (ꢁ2),
127.6 (ꢁ6), 127.7, 127.8, 127.9, 128.0, 128.2, 128.4, 128.7, 128.9 (ꢁ5),
129.0 (ꢁ4), 129.1 (ꢁ2), 132.3, 132.4 (ꢁ2), 132.6 (ꢁ2), 132.7, 132.8,
137.0, 164.0, 164.3, 164.4 (ꢁ2), 164.5, 165.3, 165.4 ppm; HR-FAB MS
[M + Na]+ calcd for C61H49FO17Na 1095.2851, found 1095.2871.
2-Benzoxazolyl 2,3,4-Tri-O-benzyl-6-O-(2,3,4,6-tetra-
O-benzyl-R/β-D-glucopyranosyl)-1-thio-β-D-glucopyrano-
side (28). The title compound was obtained from 2-thiazolinyl
2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranoside (23)15 and 2-ben-
zoxazolyl 2,3,4-tri-O-benzyl-1-thio-β-D-glucopyranoside (27)46 by method
2- thiazolinyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-glucopyranoside (23)14
and 2-benzoxazolyl 2-O-benzyl-4,6-O-benzylidene-1-thio-β-D-glucopyr-
anoside (32)43 in 70% yield. Analytical data for 33: Rf = 0.59 (ethyl
acetate/toluene, 1/4, v/v); [R]28D = +37.9° (c = 0.5, CHCl3); 1H NMR:
0
0
0
0
δ, 3.30 (m, 2H, H-6a, 6b), 3.51 (dd, 1H, J1 ,2 = 3.6 Hz, J2 ,3 = 6.9 Hz,
H-20), 3.65 (dd, 1H, J4 ,5 = 9.7 Hz, H-40), 3.75 (m, 2H, J = 5.46 Hz,
H-6a0, 6b0), 3.89ꢀ4.05 (m, 4H, H-2, 30, 4, 5), 4.20 (d, 1H, 2J = 12.0 Hz,
1/2 CH2Ph), 4.29 (dd, 1H, J3,4 = 9.0 Hz, H-3), 4.37 (m, 2H, H-50, 1/2
CH2Ph), 4.50 (d, 1H, 2J = 12.0 Hz, 1/2 CH2Ph), 4.60 (d, 1H, 2J = 12.3
Hz, 1/2 CH2Ph), 4.73ꢀ4.91 (m, 5H, 2 ꢁ CH2Ph, 1/2 CH2Ph), 5.03 (d,
0
0
1H, 2J = 10.8 Hz, 1/2 CH2Ph), 5.48 (s, 1H, >CHPh), 5.58 (d, 1H, J1,2
=
9.6 Hz, H-1), 5.70 (d, 1H, J1 ,2 = 3.6 Hz, H-10), 6.94ꢀ7.72 (m, 34H,
aromatic) ppm; 13C NMR: δ, 68.1, 68.9, 70.1, 70.7, 71.5, 73.5, 75.3, 75.9,
76.5, 78.8, 79.2, 81.9, 82.2, 85.8, 96.4, 102.4, 110.4, 119.4, 124.8, 126.6
(ꢁ3), 127.6, 127.7 (ꢁ3), 127.8, 128.0 (ꢁ3), 128.13 (ꢁ3), 128.3 (ꢁ3),
128.3 (ꢁ3), 128.4 (ꢁ3), 128.4 (ꢁ3), 128.5, 128.7, 128.8, 129.7, 136.9,
137.0, 137.8, 138.1, 138.9, 139.1, 142.0, 142.1, 142.4, 142.6, 152.1, 160.9
ppm; HR-FAB MS [M + Na]+ calcd for C61H59NO11SNa 1036.3707,
found 1036.3716.
0
0
D in 85% yield (R/β = 3.2/1) as a colorless syrup. Analytical data for 28: Rf =
1
0.52 (ethyl acetate/hexane, 3/7, v/v); H NMR; δ, 3.28 (dd, 1H, J2,3
=
0
0
0
9.8 Hz, H-2), 3.82 (dd, 1H, J3 ,4 = 9.2 Hz, H-3 ), 3.42ꢀ3.82 (m, 10H, H-3, 4,
5, 6a, 6b, 20, 40, 50, 6a0, 6b0), 4.43ꢀ4.95 (m, 14H, 7 ꢁ CH2Ph), 5.09 (d, 1H,
0
0
0
J1 ,2 = 3.5 Hz, H-1 ), 5.38 (d, 1H, J1,2 = 10.1 Hz, H-1), 7.10ꢀ7.65 (m, 39H,
aromatic) ppm; 13CNMR:δ, 65.5, 68.7, 70.4, 72.3, 73.5, 75.0, 75.3, 75.7, 75.8,
77.4, 79.8, 80.3, 80.8, 81.8, 85.0, 86.7, 97.3, 119.2, 124.4, 124.6, 127.6 (ꢁ2),
127.6 (ꢁ2), 127.7 (ꢁ2), 127.8 (ꢁ2), 127.8 (ꢁ3), 128.0 (ꢁ3), 128.0 (ꢁ3),
128.1 (ꢁ3), 128.3 (ꢁ3), 128.5 (ꢁ3), 128.5 (ꢁ3), 128.6 (ꢁ3), 128.6 (ꢁ3),
128.7 (ꢁ2), 137.7, 138.2, 138.4, 138.5, 138.7, 138.7, 138.8, 139.0, 142.0,
152.0, 161.7 ppm; HR-FAB MS [M + Na]+ calcd for C68H67NO11SNa
1128.4333, found 1128.4368.
2-Benzoxazolyl 2-O-Benzyl-4,6-O-benzylidene-3-O-(2,3,4,6-
tetra-O-benzyl-R-D-galactopyranosyl)-1-thio-β-D-galacto-
pyranoside (36). This compound was obtained by method D from
2-thiazolinyl 2,3,4,6-tetra-O-benzyl-1-thio-β-D-galactopyranoside (34) and
2-benzoxazolyl 2-O-benzyl-4,6-O-benzylidene-1-thio-β-D-galactopyranoside
(35) in 77% yield (R/β = >25/1) as a white solid. Analytical data for 36:
Rf = 0.34 (ethyl acetate/toluene, 1/4, v/v); [R]25D = +41.1° (c = 1, CHCl3);
1H NMR: δ, 3.33 (dd, 1H, J5,6a = 5.7 Hz, J6a,6b = 9.7 Hz, H-6a), 3.46 (m, 1H,
H-50), 3.43 (m, 1H, H-30), 3.51 (dd, 1H, J5,6b = 2.8 Hz, H-6b), 3.71 (m, 1H,
2-Benzoxazolyl 2,3,4-Tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-
benzoyl-β-D-glucopyranosyl)-1-thio-β-D-glucopyranoside (30).
The title compound was obtained by method D from 2-thiazolinyl 2,3,4,6-
tetra-O-benzoyl-1-thio-β-D-glucopyranoside (20)15 and 2-benzoxazolyl
2,3,4-tri-O-benzoyl-1-thio-β-D-glucopyranoside (29)43 in 76% yield as a
colorless syrup. Analytical data for 30: Rf = 0.45 (ethyl acetate/hexane,
3/7, v/v); [R]24D = +48.5° (c = 1, CHCl3); 1H NMR; δ, 3.53 (dd, 1H,
J5,6b = 8.3 Hz, H-6b), 3.86 (dd, 1H, J6a,6b = 4.8 Hz, H-6a0), 4.12 (m, 1H,
J5,6b = 2.1 Hz, H-5), 3.92 ꢀ3.99 (m, 3H, H-2, 3, 6a0), 4.07ꢀ4.19 (m, 3H, H-2,
0
4, 40), 4.28 (dd, 1H, J6b ,6a = 12.7 Hz, H-6b ), 4.33 (s, 2H, CH2Ph), 4.41 (dd,
0
0
1H, J3,4 = 7.5 Hz, H-4), 4.50ꢀ4.66 (m, 4H, 2 ꢁ CH2Ph), 4.74ꢀ4.93 (m, 4H,
2 ꢁ CH2Ph), 5.31 (d, 1H, J1 ,2 = 3.5 Hz, H-10), 5.46 (d, 1H, J1,2 = 9.9 Hz,
H-1), 5.48 (s, 1H, >CHPh), 7.10ꢀ7.47 (m, 34H, aromatic) ppm; 13CNMR:
δ, 67.7, 69.1, 70.4, 71.9, 72.2, 73.1, 73.3, 75.2, 75.4, 75,7, 76.2, 76.5, 85.4, 92.9,
110.3, 119.1, 124.4, 124.6, 126.7 (ꢁ3), 127.6, 127.7 (ꢁ4), 127.8 (ꢁ3), 127.8
(ꢁ3), 127.9 (ꢁ4), 128.2 (ꢁ4), 128.3 (ꢁ3), 128.4 (ꢁ2), 128.4 (ꢁ2), 128.5
(ꢁ4), 128.5 (ꢁ4), 128.6 (ꢁ3), 129.3, 137.9, 138.0, 138.4, 138.7, 138.9,
142.1, 152.1, 161.1 ppm; HR-FAB MS [M + Na]+ calcd for C67H59NO11SNa
1036.3707, found 1036.3704.
H-50), 4.15 (m, 1H, H-5), 4.34 (dd, 1H, J5,6b =7.9Hz, H-6b ), 4.47(dd, 1H,
0
0
0
0
0
0
0
0 0
J6a ,6b =2.6Hz, H-6a ), 4.74(m, 1H, H-2), 5.43(d, 1H,J4 ,5 =8.4Hz, H-4 ),
0
0
0
5.68 (dd, 2H, H-3, 4), 5.72 (dd, 1H, J3 ,4 =9.6Hz, H-3 ), 5.90ꢀ5.99 (m, 3H,
H-1, 10, 20), 7.09ꢀ8.10 (m, 39H, aromatic) ppm; 13C NMR: δ, 63.3, 64.4,
67.8, 68.8, 79.4, 71.0, 72.3, 74.5, 77.6, 84.3, 110.5, 119.2, 121.4, 124.9, 124.9,
126.9 (ꢁ2), 128.7 (ꢁ5), 128.8 (ꢁ5), 128.9 (ꢁ2), 129.0, 129.1, 129.2,
129.5, 129.5, 130.5 (ꢁ3), 130.1 (ꢁ5), 130.3 (ꢁ5), 130.5 (ꢁ2), 133.3,
133.7, 133.8 (ꢁ3), 133.9, 134.7, 141.9, 152.2, 164.7, 165.5, 165.5, 165.6,
166.1, 166.4 ppm; HR-FAB MS [M + Na]+ calcd for C68H53NO18SNa
1226.2281, found 1226.2283.
2-Thiazolinyl 2,3,4-Tri-O-benzyl-6-O-(2,3,4,6-tetra-O-ben-
zyl-D-glucopyranosyl)-1-thio-βꢀD-glucopyranoside (44).
The title compound was obtained by method E from ethyl 2,3,4,6-
tetra-O-benzyl-1-thio-β-D-glucopyranoside (40)40 and 2-thiazolinyl
2,3,4-tri-O-benzyl-1-thio-β-D-glucopyranoside (43)42 in 83% yield (R/
β = 1.2/1) as a colorless foam. Analytical data for 44 was in good
agreement with those reported previously.42
2-Benzoxazolyl 2,3,4-Tri-O-benzyl-6-O-(2,3,4,6-tetra-O-
benzoyl-β-D-glucopyranosyl)-β-D-glucopyranosyl)-1-thio-
βꢀD-glucopyranoside (31). This compound was obtained by
method D from 2-thiazolinyl 2,3,4,6-tetra-O-benzoyl-1-thio-β-D-glu-
copyranoside (20)14 and 2-benzoxazolyl 2,3,4-tri-O-benzyl-1-thio-β-
D-glucopyranoside (27)46 in 79% yield as a colorless syrup. Analytical
2-Thiazolinyl 2,3,4-Tri-O-benzoyl-6-O-(2,3,4-tri-O-benzoyl-6-
O-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-β-D-glucopyra-
nosyl)-1-thio-βꢀD-glucopyranoside (47). The title compound was
obtained by method E from ethyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-
benzoyl-β-D-glucopyranosyl)-1-thio-βꢀD-glucopyranoside (22)47 and
2-thiazolinyl 2,3,4-tri-O-benzoyl-1-thio-β-D-glucopyranoside (12)15 in
67% yield as a white foam. Analytical data for 47: Rf = 0.46 (ethyl
acetate/toluene, 1/4, v/v); [R]21D = +5.8° (c = 1, CHCl3); 1H NMR; δ,
3.29ꢀ3.39 (m, 2H, CH2S), 3.59 (m, 1H, H-6a0), 3.85 (m, 2H,
data for 31: Rf = 0.56 (ethyl acetate/toluene, 2/8, v/v); [R]22
=
D
ꢀ3.4° (c = 0.5, CHCl3); 1H NMR: δ, 3.44ꢀ3.73 (m, 6H, H-2, 3, 4, 5,
6a, 6b), 4.10 (m, 1H, H-50), 4.34 (dd, 1H, J6a ,6b = 12.0 Hz, J52,6a = 4.9
0
0
0
Hz, H-6a0), 4.38 (dd, 1H, J5 ,6b = 2.8 Hz, H-6b ), 4.58 (d, 1H, J = 10.8
0
0
0
Hz, 1/2 CH2Ph), 4.73ꢀ4.92 (m, 6H, H-20, 2 ꢁ CH2Ph, 1/2 CH2Ph),
5.41 (dd, 2H, J = 10.3 Hz, H-1, 40), 5.71 (m, 1H, H-30), 5.89 (d, 1H,
J1 ,2 = 5.3 Hz, H-1 ), 7.08ꢀ7.92 (m, 39H, aromatic) ppm; 13C NMR:
δ, 63.4, 64.2, 67.6, 68.7, 69.3, 72.1, 75.2, 75.7, 75.9, 76.3, 78.6, 81.0,
85.1, 86.7, 97.8, 110.21, 119.1, 121.1, 124.5, 124.6, 126.6, 127.9 (ꢁ2),
128.0 (ꢁ3), 128.1 (ꢁ2), 128.3 (ꢁ3), 128.4 (ꢁ4), 128.5 (ꢁ4), 128.6
(ꢁ4), 128.6 (ꢁ4), 129.2, 129.4, 129.86 (ꢁ3), 130.1 (ꢁ2), 130.2
(ꢁ2), 133.1, 133.7, 135.1, 137.6, 137.9, 138.4, 141.9, 151.9, 161.7,
164.6, 165.3, 166.2 ppm; HR-FAB MS [M + Na]+ calcd for
C68H59NO15SNa 1184.3503, found 1184.3490.
0
0
0
H-50,6b00), 4.00 (m, 1H, 6a00), 4.13ꢀ4.29 (m, 2H, CH2N), 4.44 (m,
00
2H, H-5, 6a0), 4.66 (m, 1H, H-6b), 4.67 (d, 1H, J1 ,2 = 7.8 Hz, H-100),
00 00
00
00 00
00 00
5.04 (dd, 1H, J4 ,5 = 9.5 Hz, H-4 ), 5.11 (dd, 1H, J2 ,3 = 7.8 Hz, H-2 ),
5.21 (d, 1H, J1 ,2 = 7.9, H-10), 5.27 (dd, 1H, J2 ,3 = 4.0 Hz, H-20),
0
0
0
0
5.59ꢀ5.62 (m, 2H, H-300, 40), 5.65 (dd, 1H, J4,5 = 8.3 Hz, H-4), 5.77 (dd,
1H, J2,3 = 7.1 Hz, H-2), 5.78 (d, 1H, J1,2 = 7.9 Hz, H-1), 5.91 (dd, 1H,
0
0
0
J3,4 = 9.6 Hz, H-3), 6.15 (dd, 1H, J3 ,4 = 9.7 Hz, H-3 ), 7.15ꢀ8.10 (m,
50H, aromatic); 13C NMR; δ, 58.8, 63.5, 64.4, 68.2, 68.4, 69.8, 69.9,
70.6, 70.8, 72.0, 72.3, 72.5, 72.9, 73.0, 74.2, 74.3, 83.5, 100.2, 101.5,
2-Benzoxazolyl 2-O-Benzyl-4,6-O-benzylidene-3-O-(2,3,4,6-
O-tetra-benzyl-R-D-glucopyranosyl)-1-thio-β-D-glucopyrano-
side (33). This compound was obtained by method D from
7396
dx.doi.org/10.1021/jo201117s |J. Org. Chem. 2011, 76, 7388–7398

The Journal of Organic Chemistry
ARTICLE
125.5 (ꢁ2), 127.2, 127.9, 128.4 (ꢁ4), 128.5 (ꢁ7), 128.6 (ꢁ6), 128.8
(ꢁ3), 128.9 (ꢁ2), 129.0, 129.1 (ꢁ4), 129.2 129.3, 129.4 (ꢁ2), 129.5,
129.8, 129.9 (ꢁ2), 130.0 (ꢁ8), 130.1(ꢁ5), 130.2 (ꢁ2), 130.3(ꢁ4),
133.3 (ꢁ2), 133.4 (ꢁ2), 133.5 (ꢁ2), 133.6 (ꢁ2), 165.2, 165.3, 165.4,
165.6 (ꢁ2), 166.0 (ꢁ2), 166.4 ppm; HR-FAB MS [M + Na]+ calcd for
C91H75NO25S2Na 1668.3967, found 1668.4023.
J = 9.8), 5.28 (dd, 1H, J = 9.3 Hz), 5.34 (d, 1H, J = 6.2 Hz), 5.40 (dd, 1H,
J = 9.7 Hz), 5.46 (m, 1H), 5.53 (dd, 1H, J = 9.5 Hz), 5.62ꢀ5.70 (m,
3H), 5.75 (dd, 1H, J = 9.6 Hz), 5.79ꢀ5.85 (m, 2H), 6.16 (dd, 1H, J =
9.6 Hz), 7.22ꢀ8.10 (m, 65H, aromatic) ppm; 13C NMR: δ, 63.4, 68.1,
68.7, 68.9, 69.1, 69.7, 69.8, 70.2, 71.7, 72.0 (ꢁ3), 72.4, 72.5, 72.8, 72.9,
73.0, 73.8, 74.2, 74.7, 100.9, 101.5, 101.7, 106.2, 128.4 (ꢁ4), 128.5
(ꢁ6), 128.6 (ꢁ6), 128.7 (ꢁ6), 128.8 (ꢁ4), 128.9 (ꢁ4), 129.0 (ꢁ2),
129.1 (ꢁ4), 129.2 (ꢁ4), 129.5 (ꢁ2), 129.7 (ꢁ2), 129.8 (ꢁ2), 129.9
(ꢁ3), 130.0 (ꢁ6), 130.1 (ꢁ6), 130.2 (ꢁ2), 133.2 (ꢁ2), 133.3 (ꢁ3),
133.4 (ꢁ2), 133.5 (ꢁ3), 133.6, 133.7, 133.8 (ꢁ2), 134.1, 165.0, 165.2,
165.3 (ꢁ2), 165.4 (ꢁ3), 165.5, 165.7, 165.9 (ꢁ2), 166.0, 166.3 ppm;
HR-FAB MS [M + Na]+ calcd for C115H93FO33Na 2043.5481, found
2043.5452.
2-Thiazolinyl 2,3,4-Tri-O-benzoyl-6-O-(2,3,4-tri-O-ben-
zoyl-6-O-(2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl)-β-
D-glucopyranosyl)-1-thio-βꢀD-glucopyranoside (49). The
title compound was obtained by method E from ethyl 2,3,4-tri-O-
benzoyl-6-O-(2,3,4,6-tetra-O-benzoyl-β-D-galactopyranosyl)-1-thio-βꢀD-
glucopyranoside (48)42 and 2-thiazolinyl 2,3,4-tri-O-benzoyl-1-thio-β-
D-glucopyranoside (12)15 in 64% yield as a white foam. Analytical data
for 49: Rf = 0.44 (ethyl acetate/toluene, 1/4, v/v); [R]24D = +12.9° (c =
1, CHCl3); 1H NMR: δ, 3.28 (m, 1H), 3.37 (m, 1H), 3.54 (dd, 1H, J =
6.5 Hz), 3.88 (m, 2H), 3.97 (m, 2H, J = 8.7 Hz), 4.06 (d, 1H, J = 10.5
Hz), 4.11 (m, 1H), 4.26 (m, 1H), 4.43 (ddd, 1H, J = 5.8, 10.9 Hz), 4.54
(dd, 1H, J = 5.9 Hz), 4.59 (m, 1H), 4.65 (d, 1H, J = 7.7 Hz), 5.04 (dd,
1H, J = 9.4 Hz), 5.15 (m, 2H, J = 8.1, 9.3 Hz), 5.55 (dd, 1H, J = 9.4 Hz),
5.64 (dd, 1H, J = 9.58 Hz), 5.69 (dd, 1H, J = 9.8 Hz), 5.77ꢀ5.83 (m,
2H), 5.86ꢀ5.92 (m, 2H), 6.02 (d, 1H, J = 2.0 Hz), 7.20ꢀ8.20 (m, 50H,
aromatic) ppm; 13C NMR: δ, 57.7, 58.8, 63.5, 64.4, 68.3, 68.8, 69.9,
70.6, 71.7, 71.6, 72.3, 72.5, 72.9, 73.1, 74.3, 74.8, 78.4, 83.5, 100.2, 102.2,
125.5 (ꢁ2), 127.3, 127.9 (ꢁ4), 128.4 (ꢁ2), 128.5 (ꢁ3), 128.5, 128.6
(ꢁ4), 128.7 (ꢁ4), 128.8, 128.9 (ꢁ3), 129.0 (ꢁ3), 129.1 (ꢁ4), 129.2
129.3, 129.4 (ꢁ2), 129.5, 129.8 (ꢁ2), 129.9, 130.0 (ꢁ2), 130.1, 130.2
(ꢁ2), 130.3 (ꢁ2), 133.4 (ꢁ4), 133.5 (ꢁ4), 133.6 (ꢁ4), 136.3 (ꢁ2),
163.0, 165.2, 165.3 (ꢁ2), 165.5 (ꢁ2), 165.7 (ꢁ2), 165.9, 166.2 ppm;
HR-FAB MS [M + Na]+ calcd for C91H75NO25S2Na 1668.3967, found
1668.3940.
Ethyl O-(2,3,4-Tri-O-benzoyl-β-D-glucopyranosyl)-(1f6)-
O-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-(1f6)-O-
(2,3,4-tri-O-benzoyl-β-D-glucopyranosyl)-(1f6)-O-(2,3,
4-tri-O-benzoyl-β-D-glucopyranosyl)-(1f6)-2,3,4-tri-O-ben-
zoyl-1-thio-β-D-glucopyranoside (53). The compound was ob-
tained by method F from 52 and ethyl 2,3,4-tri-O-benzoyl-thio-β-D-
glucopyranoside (21)48 in 84% yield as a white solid. Analytical data for
53: Rf = 0.46 (ethyl acetate/toluene, 1.5/8.5, v/v); [R]26D = ꢀ9.3° (c =
1, CHCl3); 1H NMR: δ, 1.14 (t, 3H, SCH2CH3), 2.68 (m, 2H,
SCH2CH3), 3.58 (m, 1H, J = 5.5, 6.2 Hz), 3.67ꢀ3.75 (m, 3H),
3.85ꢀ3.92 (m, 6H), 4.02 (dd, 1H, J = 10.8 Hz), 4.12 (m, 1H), 4.35
(m, 1H), 4.48 (dd, 1H, J = 5.5, 12.1 Hz), 4.57 (dd, 1H, J = 11.0 Hz), 4.70
(d, 1H, J = 10.0 Hz), 4.76 (d, 1H, J = 7.7 Hz), 4.86 (m, 2H), 5.16 (d, 1H,
J = 7.9 Hz), 5.25 (dd, 1H, J = 9.6 Hz), 5.33 (dd, 1H, J = 9.3 Hz), 5.39 (dd,
1H, J = 9.6 Hz), 5.43ꢀ5.56 (m, 7H), 5.70 (dd, 1H, J = 9.7 Hz),
5.76ꢀ5.87 (m, 2H), 5.90ꢀ5.95 (m, 2H), 6.23 (dd, 1H, J = 9.7 Hz),
6.95ꢀ8.90 (m, 80H, aromatic) ppm; 13C NMR: δ, 14.9, 31.1, 63.5, 68.0
(ꢁ2), 69.0, 69.3, 69.7, 69.9, 70.1, 70.2, 70.7, 71.0, 72.2, 72.3, 72.4, 72.5
(ꢁ2), 72.7, 72.8, 73.0 (ꢁ2), 73.8, 74.2, 74.7, 78.4, 83.7, 101.2, 101.3,
101.4, 101.8, 128.2 (ꢁ3), 128.3 (ꢁ5), 128.4 (ꢁ6), 128.5 (ꢁ4), 128.6
(ꢁ3), 128.7 (ꢁ6), 128.8 (ꢁ3), 128.9 (ꢁ4), 129.0 (ꢁ4), 129.1 (ꢁ3),
129.2 (ꢁ4), 129.3 (ꢁ2), 129.5 (ꢁ2), 129.7 (ꢁ4), 129.8 (ꢁ7), 129.9
(ꢁ4), 130.0 (ꢁ9), 130.1 (ꢁ10), 133.1 (ꢁ2), 133.2 (ꢁ2), 133.3 (ꢁ2),
133.4 (ꢁ3), 133.5 (ꢁ2), 133.6, 133.8, 165.2 (ꢁ2), 165.3 (ꢁ3), 165.4
(ꢁ2), 165.6 (ꢁ2), 165.8, 165.9 (ꢁ4), 166.0, 166.3 ppm; HR-FAB MS
[M + Na]+ calcd for C144H120O41SNa 2559.6923, found 2559.6938.
4-Pentenyl O-(2,3,4-Tri-O-benzoyl-β-D-glucopyranosyl)-
(1f6)-O-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-(1f6)-
O-(2,3,4-tri-O-benzoyl-β-D-glucopyranosyl)-(1f6)-O-(2,3,4-tri-
O-benzoyl-β-D-glucopyranosyl)-(1f6)-O-(2,3,4-tri-O-benzoyl-
β-D-glucopyranosyl)-(1f6)-2,3,4-tri-O-benzoyl-β-D-glucopyr-
anoside (55). This compound was obtained by method C from 53 and
4-pentenyl 2,3,4-tri-O-benzoyl-β-D-glucopyranoside (54)16 in 72% yield
as a white solid. Analytical data for 53: Rf = 0.50 (ethyl acetate/toluene,
2/8, v/v); [R]22D = ꢀ10.5° (c = 1, CHCl3), 1H NMR: δ, 1.41ꢀ1.58 (m,
4H), 1.89 (m, 2H), 3.28 (m, 1H), 3.55 (m, 2H), 3.71 (dd, 1H, J = 11.5
Hz), 3.75ꢀ3.81 (m, 5H), 3.90ꢀ4.07 (m, 7H), 4.12 (m, 1H), 4.31 (m,
1H), 4.47 (dd, 1H, J = 5.4, 12.1 Hz), 4.56 (dd, 1H, J = 2.6, 9.3 Hz), 4.64 (d,
1H, J = 7.9 Hz), 4.75 (d, 1H, J = 1.6 Hz), 4.79ꢀ4.87 (m, 6H), 5.12 (d, 1H,
J = 7.8 Hz), 5.24 (dd, 1H, J = 9.7 Hz), 5.31 (dd, 1H, J = 1.8, 9.6 Hz),
5.38ꢀ5.55 (m, 9H), 5.58ꢀ5.63 (m, 1H), 5.68 (dd, 1H, J = 9.7 Hz), 5.67
(dd, 1H, J = 9.7 Hz), 5.86 (dd, 1H, J = 9.6 Hz), 5.90 ꢀ5.97 (m, 2H, J = 9.6
Hz), 6.06 (dd, 1H, J = 9.6 Hz), 6.16 (dd, 1H, J = 9.7 Hz), 6.90ꢀ8.00 (m,
95H, aromatic) ppm; 13C NMR: δ, 28.7, 29.9, 30.0 (ꢁ2), 31.1, 63.0, 63.4,
67.6, 68.2, 69.8, 69.9, 70.1, 70.5 (ꢁ2), 70.9 (ꢁ2), 72.1 (ꢁ2), 72.3 (ꢁ2),
72.4 (ꢁ3), 72.8 (ꢁ2), 72.9, 73.0 (ꢁ2), 74.5, 89.9 (ꢁ2), 101.2, 101.3
(ꢁ3), 101.4, 101.6, 115.0, 128.2 (ꢁ5), 128.3 (ꢁ5), 128.4 (ꢁ5), 128.5
(ꢁ7), 128.6 (ꢁ5), 128.7 (ꢁ6), 128.8 (ꢁ7), 129.00 (ꢁ10), 129.1 (ꢁ6),
129.2 (ꢁ6), 129.3 (ꢁ4), 129.4 (ꢁ4), 129.7 (ꢁ4), 129.8 (ꢁ8), 129.9
(ꢁ6), 130.0 (ꢁ12), 130.1 (ꢁ12), 130.2 (ꢁ6), 165.2 (ꢁ3), 165.3, 165.4
(ꢁ3), 165.5 (ꢁ2), 165.6 (ꢁ2), 165.7, 165.9 (ꢁ4), 166.0, 166.3 ppm;
2-Benzoxazolyl 2,3,4-Tri-O-benzoyl-6-O-(2,3,4-tri-O-ben-
zoyl-6-O-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-β-D-
glucopyranosyl)-1-thio-βꢀD-glucopyranoside (51). The title
compound was obtained by method D from 14 and 2-benzoxazolyl
2,3,4-tri-O-benzoyl-1-thio-β-D-glucopyranoside (29)43 in 67% yield as a
colorless syrup. Analytical data for 51: Rf = 0.48 (ethyl acetate/toluene,
1.5/8.5, v/v); [R]28D = +47.4° (c = 1, CHCl3); 1H NMR: δ, 3.43ꢀ3.45
0
0
0
0
0
(m, 2H, H-6a, 6b), 3.66 (dd, 1H, J5 ,6a = 5.5 Hz, J6a ,6b = 11.5 Hz, H-6a ),
3.84 (m, 1H, H-50), 4.06ꢀ4.16 (m, 3H, H-5, 500, 6b0), 4.30 (dd, 1H,
00
00
00
00
00
00
J5 ,6a = 5.1 Hz, J6a ,6b = 12.1 Hz, H-6a ), 4.54ꢀ4.58 (m, 2H, H-4, 6b ),
0
0
0
0
4.95 (d, 1H, J1 ,2 = 11.0 Hz, H-1 ), 5.22 (dd, 1H, H-4 ), 5.50ꢀ5.55 (m,
2H, H-20, 30), 5.60ꢀ5.69 (m, 2H, H-300, 400), 5.71 (dd, 1H, J3,4 = 9.6 Hz,
H-3), 5.77 (d, 1H, J1 ,2 = 5.3 Hz, H-100), 5.86 (dd, 1H, J2,3 = 9.7 Hz,
00 00
00 00
H-2), 5.95 (d, 1H, J2 ,3 = 9.5 Hz), 5.96 (d, 1H, J1,2 = 10.3 Hz, H-1),
7.15ꢀ8.10 (m, 54H, aromatic) ppm; 13C NMR: δ, 60.6, 63.0, 63.3, 68.1,
68.6, 69.3, 69.5, 70.0, 70.8, 71.7, 72.4, 72.4, 73.2, 74.3, 76.7, 77.6, 77.7,
84.1, 97.8, 102.0, 110.3, 119.1, 121.1, 124.6, 124.8, 126.6, 128.2 (ꢁ2),
128.4 (ꢁ2), 128.4 (ꢁ2), 128.5 (ꢁ4), 128.6 (ꢁ4), 128.8, 128.9, 129.0,
129.1, 129.1, 129.2, 129.4 (ꢁ3), 129.7, 129.8 (ꢁ2), 129.9 (ꢁ4), 130.0
(ꢁ4), 130.0 (ꢁ4), 130.0 (ꢁ4), 130.10 (ꢁ2), 130.3, 133.1, 133.2, 133.3
(ꢁ2), 133.4, 133.5, 133.6 (ꢁ2), 133.6, 134.4, 141.7, 152.0, 161.4, 164.5,
165.1, 165.2, 165.2, 165.4, 165.9, 166.0, 166.3 ppm; HR-FAB MS [M +
Na]+ calcd for C95H75NO26SNa 1700.4196, found 1700.4182.
O-(2,3,4-Tri-O-benzoyl-β-D-glucopyranosyl)-(1f6)-O-(2,3,4,
6-tetra-O-benzoyl-β-D-glucopyranosyl)-(1f6)-O-(2,3,4-tri-
O-benzoyl-β-D-glucopyranosyl)-(1f6)-2,3,4-tri-O-benzoyl-
β-D-glucopyranosyl Fluoride (52). The title compound was
obtained by method C from 51 and 2,3,4-tri-O-benzoyl-β-D-glucopyr-
anosyl fluoride (18)45 in 87% yield as a colorless syrup. Analytical data
for 52: Rf = 0.42 (ethyl acetate/toluene, 1/9, v/v); [R]25D = ꢀ2.0° (c =
1, CHCl3); 1H NMR: δ, 3.54 (m, 1H), 3.59 (m, 1H), 3.86 (m, 3H),
4.00ꢀ4.08 (m, 3H), 4.14 (dd, 1H, J = 12.1 Hz), 4.34 (m, 1H), 4.46 (dd,
1H, J = 4.9, 11.4 Hz), 4.60 (dd, 1H, J = 11.8 Hz), 4.76 (d, 1H, J = 7.7
Hz), 4.82 (d, 1H, J = 7.9 Hz), 5.11 (d, 1H, J = 7.8 Hz), 5.21 (dd, 1H,
7397
dx.doi.org/10.1021/jo201117s |J. Org. Chem. 2011, 76, 7388–7398

The Journal of Organic Chemistry
ARTICLE
HR-FAB MS [M + Na]+ calcd for C174H146O50Na 3057.8780, found
3057.8748.
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Supporting Information. 1H and 13C NMR spectra for
S
b
all new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
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’ AUTHOR INFORMATION
Corresponding Author
*E-mail: demchenkoa@umsl.edu.
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’ ACKNOWLEDGMENT
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This work was supported by awards from NIGMS
(GM077170) and NIAID (AI067494). Dr. Winter and Mr. Kramer
(UMꢀSt. Louis) are thanked for HRMS determinations.
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