Application of 2-substituted benzyl groups in stereoselective glycosylation

Article abstract of DOI:10.1021/jo502186f

The use of 2-O-(2-nitrobenzyl) and 2-O-(2-cyanobenzyl) groups controls stereoselective formation of 1,2-trans-glycosidic linkages via the arming participation effect. The observed stereoselectivity likely arises from the intramolecular formation of cyclic intermediate between the electron-rich substituent and the donor oxacarbenium ion providing the expected facial selectivity for attack of the glycoside acceptor. The stereodirecting effect of the 2-nitro- and 2-cyanobenzyl groups attached at the remote position (C-3, C-4, and C-6) of the donor molecule have also been investigated. To prove the postulated mechanism based on the participation effect of 2-substituted benzyl groups in the glycosylation stereoselectivity we used DFT theoretical calculation methodology.

Full text of DOI:10.1021/jo502186f

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Article
Application of 2-Substituted Benzyl Groups in Stereoselective Glycosylation
Szymon Buda, Miros#aw Nawój, Patrycja Go##biowska, Karol Dyduch, Artur Michalak, and Jacek Mlynarski
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo502186f • Publication Date (Web): 18 Dec 2014
Downloaded from http://pubs.acs.org on December 19, 2014
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Application of 2-Substituted Benzyl Groups in Stereoselective Glycosylation
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Szymon Buda, Mirosław Nawój, Patrycja Gołębiowska, Karol Dyduch, Artur Michalak and
Jacek Mlynarski*
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Faculty of Chemistry, Jagiellonian University, Ingardena 3, 30ꢀ060 Krakow
Eꢀmail: jacek.mlynarski@gmail.com.
TOC Graphic
Abstract: The use of 2ꢀOꢀ(2ꢀnitrobenzyl) and 2ꢀOꢀ(2ꢀcyanobenzyl) groups control
stereoselective formation of 1,2ꢀtransꢀglycosidic linkage via arming participation effect.
Observed stereoselectivity arise likely from the intramolecular formation of cyclic
intermediate between electron rich substituent and donor oxacarbenium ion providing
expected facial selectivity for the attack of the glycoside acceptor. The stereodirecting effect
of the 2ꢀnitroꢀ and 2ꢀcyanobenzyl groups attached at remote position (Cꢀ3, Cꢀ4, and Cꢀ6) of
donor molecule have also been investigated. To prove postulated mechanism based on
participation effect of 2ꢀsubstituted benzyl groups in the glycosylation stereoselectivity we
used DFT theoretical calculation methodology.
Introduction
Because of the importance and prominent role the oligosaccharides play in biology and
pharmaceutical industry, stereoselective formation of glycosidic bond are probably the most
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important aspect of modern carbohydrate chemistry.1 Despite many various strategies
available for the efficient and stereocontrolled synthesis diꢀ and oligosaccharides, this field
still deserves additional attention.2 The most commonly used strategy for the synthesis of
glycosidic bond involves nucleophilic coupling of suitably protected glycosyl acceptor (ROH)
with fully protected donor bearing a leaving group (LG) at its anomeric center.3 Nucleophilic
attack of a hydroxyl moiety of a glycosyl acceptor to the flattened oxacarbenium ion resulting
from the leaving group departure often leads to usually undesired αꢀ and βꢀanomers mixture.4
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Stereocontrolled synthesis of one anomer requires special techniques, among whose
the most reliable is selective equipment of donor molecule with the groups controlling
glycosylation via intramolecular stereodirecting effects. Thus, the most studied application of
2ꢀOꢀacyl functionality (Scheme 1, I) depends on neighboring group participation of ester
protecting group which gives a more stable oxacarbenium ion shielded by protecting group
from one site. An alcohol can attack the anomeric center from only one face providing 1,2ꢀ
transꢀglycoside. However, application of esterꢀtype substituents which electronically
deactivate donor molecule decrease the reaction yield, in many cases. In contrast, application
of etherꢀtype substituent (Scheme 1, II) which electronically activate donor usually lead to a
mixture of both anomers, resulting from unhindered approach of alcohol from both sites of
flattened oxacarbonium ion.
Interestingly, application of an electronꢀrich etherꢀtype substituent which could control
glycosylation via neighboring group participation has been neglected for many years. In 2005,
Demchenko demonstrated 1,2ꢀtrans glycosylation by developing the neighboring 2ꢀOꢀ
picolinyl (pyridylmethyl) ether.5 Pyridineꢀbased Nꢀdonor was demonstrated to be capable of
efficient participation when attached at Cꢀ2, but also at Cꢀ3, Cꢀ4, and Cꢀ6 position of glycosyl
donor.6 In the case of remote picolinyl substituent authors postulate intermolecular Hꢀbond
tethering with glycosyl acceptor instead of direct participation of nitrogen atom to anomeric
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position.6 Stereoselective 1,2ꢀcis glycosides by using (S)ꢀ(phenylthiomethyl)benzyl and 2ꢀOꢀ
(thiophenꢀ2ꢀyl)methyl protecting group have been demonstrated by Boons7 and Fairbanks,8
respectively. According to authors, observed αꢀselectivity results from the intramolecular
formation of a transition sixꢀmembered intermediate sulfonium/thiophenium ion, which then
undergoes nucleophilic substitution by the glycosyl acceptor from the αꢀsite. In parallel, some
other nonꢀbenzyl groups for participationꢀassisted or stereodirectiong glycosylation have been
recently introduced.9 In contrast, successful examples of regular benzyl ethers substituted at
aromatic ring (Scheme 1, III) have never been deeply explored. This concept, however, seems
to have great potential and the use of neighboring participation by using benzylꢀtype group
may have important impact on the field by combining at least two advantages: the use of
activated (armed) donor and easy oneꢀstep deprotection of all benzylꢀtype groups at the most
convenient stage.
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Here, we report the first use of 2ꢀsubstituted benzyl groups as stereodirecting
substituents for the formation of 1,2ꢀtransꢀglycosidic linkage. As the benzyls can be removed
after glycosylation, they can be used as stereodirecting protecting groups broadly expending
application of benzyl groups in carbohydrate chemistry and chemical glycosylation.
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Scheme 1. Glycosyl Donors with 2ꢀOꢀAcetylꢀ(1a), 2ꢀOꢀBenzylꢀ(1b), 2ꢀOꢀ(2ꢀNitrobenzyl)ꢀ
(1c) and 2ꢀOꢀ(2ꢀCyanobenzyl)ꢀ(1d) Groups
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Results and Discussion
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Previously we showed that that 1,2ꢀtrans stereoselectivity in glycosylation can be achieved by
using 2ꢀOꢀ(2ꢀnitrobenzyl) which can act as a neighboring glycosylation support of type III
(Scheme 1).10 Assuming that other substituted benzyl groups can show similar features and
takin into account relatively low stability of nitrobenzyl ethers we decided to broaden the
scope of this method and investigate whether similar effect can be achieved by using other
benzyl ethers. After initial trials we selected 2ꢀcyanobenzyl as comparatively promising
candidate to nitrobenzyl. Different geometry and electronic nature of both groups and
different availability of electron pairs further encouraged for comparison of both benzyl
groups. Moreover, in contrast to wellꢀknown external nitrile effect,11 discovering of similar
influence of cyano substituent from the same sugar remote position seemed to be highly
exciting.
As the starting comparison points, we decided to use perꢀOꢀbenzylated thioglucoside
1b and 2ꢀOꢀ(2ꢀnitrobenzyl)ꢀ(1c) as well as 2ꢀOꢀ(2ꢀcyanobenzyl) thioglucoside (1d) donors.
Both benzyl ethers (NBn, CNBn) could be efficiently prepared from the corresponding
alcohols by using routine methodology as that used for regular benzyl ehers. All three donors
1bꢀd as well as 2ꢀOꢀ(acetyl) thioglucoside (1a) were activated by treatment with Ph2SO and
triflic anhydride (Tf2O) in the presence of 2,4,6ꢀtriꢀtertꢀbutylꢀpyridine (TTBP) in
dichloromethane as a standard condition,12 and coupled with methanol to afford methyl
glucoside 2aꢀd (Table 1). According to expectation, glycosidation of donor 1a resulted in
exclusive formation of βꢀmethyl glucoside 2a although in low yield (44%) as combining
effect of disarming participating effect of ester substituent (Table 1, entry 1). In contrast,
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glycosidation of perꢀOꢀbenzylated donor 1b was more efficient yet unselective leading to a
mixture of both anomers in (1:1) ratio (Table 1, entry 2). This significant example of
unselective glycosylation in the presence of regular benzyl ether attached to Cꢀ2 position of
donor constitutes comparison point for forthcoming substituted benzyl groups. Indeed,
reactions of both 2ꢀOꢀ(2ꢀnitrobenzyl)ꢀ(1c) and 2ꢀOꢀ(2ꢀcyanobenzyl)ꢀ(1d) thioglucosides
turned out to be far more stereoselective. The desired 1,2ꢀtrans methyl glycosides 2c and 2d
were isolated in high yields and with high level of βꢀselectivity (Table 1, entries 3 and 4) thus
confirming assumed arming as well as participating effect of both substituted benzyl groups.
The reactions with donors 1c/1d methanol as acceptor proceed selectively in range of solvents
additionally proved prominent internal effect of 2ꢀnitroꢀ and 2ꢀcyanosubstituents.13
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Table 1. Glycosylation Reaction of Donors Containing Various 2ꢀOꢀSubstituents with
Methanol.
Donor
Product
Yield [α/β]
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2
44% (0:1)
91% (1:1)
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95% (1:12)
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82% (1:12)
Reaction were performed with donor 1aꢀd (0.074 mmol), MeOH (0.11 mmol), Ph2SO (0.081
mmol), TTBP (0.185 mmol), DCM (5 ml) at –40 °C to r.t. for 3 h.
The same series of donors 1aꢀd have been submitted to more demanding glycosylation
with methyl 2,3,4ꢀtriꢀOꢀbenzylꢀαꢀDꢀglucopyranoside (3) having primary hydroxyl group at Cꢀ
6. Results of this trialꢀbyꢀfire for new benzyl ethers have been collected in Table 2.
Glycosylation with 1a as acceptor produced disaccharide 4a in a modest yield but with
complete βꢀstereoselectivity (Table 2, entry 1). Glycosylation of donors 1bꢀ1d showed that
the stereoselectivity of glycosylation was highly dependent on the electronic structure of
benzyl ether at Cꢀ2. However with all three armed donors yield of isolated disaccharides (4bꢀ
4d) were high the βꢀstereoselectivity of the process was considerable for 2ꢀOꢀ(2ꢀnitrobenzyl)ꢀ
(1c) and 2ꢀOꢀ(2ꢀcyanobenzyl)ꢀ(1d) thioglucosides only (Table 2, entries 2 vs. 3,4). The fact
that the glycosylation lead principally to the formation of βꢀanomers provides strong support
that the reactions proceed through neighboring participation of substituted benzyl ethers from
αꢀsite of anomeric position in donor ring. The stereocontrolling effect of the 2ꢀnitrobenzylꢀ
and 2ꢀcyanobenzyl groups were accompanied by a great influence on general reaction yield
(Table 2, entry 1 vs. 3,4) which may be referred to arming effect of newly used benzyl ethers
(NBn and CNBn).
Table 2. Glycosylation Reaction with 6ꢀOH Acceptor 3
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Donor
Product
Yield [α/β]
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2
42% (0:1)
60% (1:1)
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4
88% (1:3)
86% (1:3)
Reaction were performed with donor 1aꢀd (0.074 mmol), acceptor 3 (0.11 mmol), Ph2SO
(0.081 mmol), TTBP (0.185 mmol), DCM (5 ml) at –40 °C to r.t. for 3 h.
Subsequent investigations focused on glycosylation of donor 1d with 2ꢀcyanobenzyl
groups as relatively more stable and synthetically more useful when compared to 2ꢀnitroꢀ
counterpart. More investigations and results with donor 1c have been presented in our
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previous work.10 The synthetic scope of the current 2ꢀcyanobenzyl protecting group was
examined by changing the structure of acceptors (Table 3). The glycosylation of 1d with 5,
which has a secondary hydroxyl group at Cꢀ4, proceed smoothly and afforded the desired Oꢀ
glycoside 8 with high βꢀselectivity and high yield (Table 3, entry 1). The glycosylation of 1d
with 6 and 7, which have equatorially hydroxyl group at Cꢀ2 and Cꢀ3, respectively, also
afforded disaccharides 9 and 10 with predominant formation of βꢀanomers (Table 3, entries 2
and 3). Reaction of nonꢀsugar alcohols (propan2ꢀol, benzyl alcohol and nonanꢀ1ꢀol)
proceeded even better, and resulted in a formation of expected βꢀanomers, exclusively (Table
3, entries 4ꢀ6).
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Table 3. Example of Various Glycosyl Acceptors Tested in Glycosylation with Donor 1d
Acceptor
Product
Yield (α/β)
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67% (1:5)
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MeO
O
O
O
O
O
Ph
34% (1:5)
BnO
BnO
OBn
OCNBn
OBn
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72% (1:4)
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propan-2-ol
benzyl alcohol
nonan-1-ol
78% (0:1)
67% (1:10)
54% (0:1)
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6
R1 = iPr
R1 = Bn
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R1 = C9H19
Reaction were performed with donor 1d (0.074 mmol), acceptor (0.11 mmol), Ph2SO (0.081
mmol), TTBP (0.185 mmol), DCM (5 ml) at – 40 °C to r.t for 3 h.
In order to prove the applicability of the new methodology in organic synthesis we
examined possibility of mild deprotection of thus utilized 2ꢀbenzyl ethers from glucoside 2c
and 2d (Scheme 1). Both ethers were easily cleaved when using standard debenzylation
conditions (H2/PdꢀC). This methodology can be used for convenient deprotection of all benzyl
substituents when necessary. Additionally, 2ꢀnitrobenzyl protecting group can be also
selectively cleaved in the presence of other benzyl groups by light irridation14 affording
methyl 3,4,6ꢀtriꢀOꢀbenzylꢀβꢀDꢀglucopyranoside (14) in high yield. This mild deprotection
method can further open up new areas of application of 2ꢀnitrobenzyl as arming participating
protecting group.
Scheme 2. Pd/C Hydrogenation and Selective UVꢀlight Deprotection of 2ꢀNitrobenzyl Group
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This successful application of 2ꢀnitrobenzyl (NBn) and 2ꢀcyanobenzyl (CNBn) as
arming participating groups controlling 1,2ꢀtransꢀglycosidic bond formation rely on the
assumption of neighboring group participation of both tested benzyl ethers. Thus, we
postulate that the oxocarbenium ion is controlled as a stable intermediate by electrons of 2ꢀOꢀ
CNBn (Scheme 3) or 2ꢀOꢀNBn protecting group. Formal participation of the nitrogen (CN) or
oxygen (NO2) will give a more stable oxacarbenium ion providing βꢀglycosides after alcohol
attack from only one face providing 1,2ꢀtransꢀglycoside (Scheme 3).
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Scheme 3. Proposed Participating Group Concept by Using Cyanobenzyl Group
To exclude alternative explanations,15 and to prove previously postulated mechanism
based on participation of 2ꢀsubstituted benzyl groups in the glycosylation, we used DFT
theoretical calculation methodology. The main goal of the theoretical (DFT) calculations was
to investigate the electronic structure of the cationic form of IV (see Scheme 2) with and
without presence of leaving anion (OTf), to verify the possibility of formation of an intraꢀ
molecular bond between the nitrile group and the cationic carbon centre. The minimum
energy structure of the cation is shown in Figure 1, structure A. In the absence of anion, a
strong, ‘single’ bond between nitrogen atom from nitrile group and carbon from glucose ring
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is formed: the distance is 1.506Å, and the calculated bondꢀorder is 0.968. As the result, the
carbonꢀnitrogen bond in nitrile group can be described as ‘double’ bond, with the bond order
of 2.110, and the bond length equal to 1.236Å. In addition, the significant interaction between
the carbon atom of nitrile group and the ether oxygen can be observed, characterized by the
bond order value of 0.670 and the distance of 1.625Å. This may result from shifting electron
density toward glucose ring and formation of a partial positive charge on the nitrile carbon
atom. Thus, in the cationic structure A two additional fiveꢀmember rings are observed.
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For neutral systems in which cationic glucose derivative is neutralized by OTf anion,
two low energy structures were obtained from geometry optimization, presented in Figure 1
(panels B and C). Here, the structure with unbounded nitrile group is slightly lower in energy
(by c.a. 1 kcal/mol), than the structure in which the bond between the nitrile nitrogen and the
glucose carbon atom is preserved. However, since the energy difference is relatively low
(below 1 kcal/mol), it can be expected that these structures can coexist.
Two conclusions emerge from comparison of the structures presented in Figure 1.
Firstly, the bond between oxygen atom of OTf anion and the respective glucose carbon is
longer/weaker in structure B (bond length: 1.525Å; bond order: 0.908) than in structure C
(bond length: 1.413Å; bond order: 1.077). Secondly, the comparison of structures A and C
leads to a conclusion that the interaction between cationic species and anion results in
strengthening of nitrogenꢀcarbon bond for C (increase in bond order from 0.968 to 1.065),
while for structure B such interaction is not observed ꢀ the distance between nitrogen atom
and glucose carbon is 5.871Å. These results support our assumption about participation of the
nitrogen of CN group via formation of CꢀN bond with anomeric center of the oxacarbenium
ion efficiently shielding αꢀface providing 1,2ꢀtransꢀglycoside (Scheme 3).
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Figure 1. Comparison of bond lengths (top value) and bond orders (bottom value) for
optimized models of structure I for cationic molecule (panel A), and neutral systems
including anion (panels B and C). For structures B and C, the electronic energy difference is
also presented.
In order to draw qualitative conclusions concerning the interaction of the analyzed
system with nucleophiles, the molecular electrostatic potential (MEP) was characterized for
compounds B and C, the colourꢀcoded contour is presented in Figure 2. A comparison clearly
shows that in the vicinity of the respective carbon atom undergoing the nucleophilic attack,
the MEP is more positive for structure C than for B. Thus, it may be predicted, that the
structure C will be more reactive towards nucleophilic attack. This further strengthens the
conclusion about the importance of the intraꢀmolecular bond between the nitrile nitrogen atom
and the carbon atom of glucose, as a possible origin of the experimentally observed
stereoselectivity.
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Figure 2. Molecular Electrostatic Potential (MEP), colourꢀcoded on the electron density
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isosurface (ρ = 0.001 a.u.) for structures B (left) and C (right); the arrow points to the
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respective carbon atom that can be attacked by a nucleophile in the glycosylation reaction
mechanism.
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It was also interesting whether participating effect of 2ꢀsubstituted benzyl groups
could be visible from remote positions of donors. The effect that these remote substituents
may have on the reaction stereoselectivity was estimated at this stage. To asses this
possibility, we tested a series of novel glycosyl donors equipped with 2ꢀnitrobenzyl (NBn)
and 2ꢀcyanobenzyl (CNBn) groups at remote positions i.e. Cꢀ6 (16, 17), Cꢀ4 (18, 19) and Cꢀ3
(20, 21). Results of this study collected in Table 4 showed that observed level of
stereoselectivity controlled by remote benzyl groups is not exceptionally high, while
formation of either
thioglycoside 18 and 19 gave disaccharide 24 and 25 with reversed
entry 1). In contrast, isomers with 4ꢀ ꢀsubstituted benzyl groups 18 and 19 showed tendency
for predominant formation of ꢀglycosides 24 and 25 (Table 4, entry 2) while 3ꢀ ꢀsubstituted
αꢀ or
β
ꢀanomers supported our assumptions. Thus, 6ꢀ
Oꢀequiped
αꢀselectivity (Table 4,
O
β
O
donors were simply unselective (Table 4, entry 3).
Table 4. Example of Remote Control in Glycosylation.
O
OMe
OBn
O
O
O
OMe
OBn
Ph2SO, TTBP
Tf2O
H O
BnO
R1 =
R1O
R2O
donor
16-21
OBn
DCM,
molecular sieves
BnO
OBn
OR3
OBn
3
22-27
Donor
Product
Yield [α/β]
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73% (2:1)
85% (2:1)
22: R1=NBn, R2=R3=Bn
23: R1=CNBn, R2=R3=Bn
1
2
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79% (1:3)
93% (1:2)
24: R2=NBn, R1=R3=Bn
25: R2=CNBn, R1=R3=Bn
98% (1:1)
80% (1:1)
26: R3=NBn, R1=R2=Bn
27: R3=CNBn, R1=R2=Bn
3
Reaction were performed with donor 16ꢀ21 (0.074 mmol), 3 (0.11 mmol), Ph2SO (0.081
mmol), TTBP (0.185 mmol), DCM (5 ml) at –40 °C to r.t. for 3 h.
Explanation for various modes of participating group effect is showed in Scheme 3. 2ꢀ
Nitro and 2ꢀcyano substituted benzyl groups attached to Cꢀ4 position can interact with
oxacarbenium ion in cisꢀfacial relation providing expected
glycoside acceptor. Direct interaction between 6ꢀ ꢀsubstituted benzyl groups with anomeric
center resulted in predominant formation of ꢀglycosides (Scheme 4) while nonꢀselective
reaction of 3ꢀ ꢀsubstituted thioglycoside resulted from ineffective shielding interaction of
substituent and anomeric center.
βꢀselectivity for the attack of the
O
α
O
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Scheme 4. Remote Participation of 2ꢀcyanoꢀ and 2ꢀnitrobenzyl Groups
Conclusions
In summary, we presented that 2ꢀsubstituted benzyl protecting groups can efficiently control
stereoselective formation of 1,2ꢀtransꢀglycosidic linkage thus acting as armed participating
groups. We demonstrated that 1,2ꢀtransꢀstereoselectivity can be achieved by using 2ꢀ
Oꢀ(2ꢀ
nitrobenzyl) and 2ꢀ ꢀ(2ꢀcyanobenzyl) ethers, which can act as neighboring glycosylation
O
support. This ether group can also enhance the reaction yield by activation (arming) glycosyl
donors, in contrast to broadly used deactivating esters. Similar yet lower stereoselectivity can
be achieved by using remote benzyl groups. Easy protection and selective deprotection of
presented 2ꢀnitrobenzyl 2ꢀcyanobenzyl group further confirms its usefulness in the synthesis.
Experimental Section
General Information. All starting materials and reagents were obtained from commercial
sources and used as received unless otherwise noted. All solvents used were freshly distilled
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prior to use. Optical rotations were measured at room temperature with a polarimeter. Highꢀ
resolution mass spectra were acquired using electrospray (ESI) ionization mode with a timeꢀ
1
ofꢀflight (TOF) detector. H NMR spectra were recorded on spectrometers operating at 300,
9
500 and 600 MHz in CDCl3. Data were reported as follows: chemical shifts in parts per
million (ppm) from tetramethylsilane as an internal standard, integration, multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, dd = doubleꢀdoublet, m = multiplet, br = broad),
coupling constants (in Hz), and assignment. 13C NMR spectra were measured at 75, 125 or
150 MHz with complete proton decoupling. Chemical shifts were reported in ppm from the
residual solvent as an internal standard. Reactions were controlled using TLC on silica
[aluꢀplates (0.2 mm)]. Plates were visualized with UV light (254 nm) and by treatment with:,
aqueous cerium(IV) sulfate solution with molybdic and sulfuric acid followed by heating. All
organic solutions were dried over anhydrous sodium sulfate. Reaction products were purified
by flash chromatography using silica gel 60 (240ꢀ400 mesh).
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All the DFT calculations presented here are based on the Amsterdam Density Functional
(ADF2013) program.16ꢀ19 Structures were fully optimized using the BeckeꢀPerdew exchangeꢀ
correlation functional (BP86).20,21 For obtained geometries dispersion correction to energy
was calculated using BP86ꢀD3 with BeckeꢀJohnson Damping.22,23 Full electron basis set with
a tripleꢀzeta STO basis containing two sets of polarization functions, was adopted for all of
the elements (TZ2P). Auxiliary s, p, d, f and
g STO functions, centered on all nuclei, were
used to fit electron density and obtain accurate Coulomb potentials in each SCF cycle.
Relativistic effects were included using the ZORA formalism. The contours and the colorꢀ
coded plots of the molecular electrostatic potential were plotted based on ADFꢀGUI
interface.24 NalewajskiꢀMrozek bondꢀmultiplicity indices25,26 implemented in ADF program
were used to quantify selected bondꢀorders.
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Synthesis and spectroscopic data for compound 1a-1c, 2a-c, 3, 4a-c, 14, 15 were described
previously.10 Synthesis of known compound 5 have been performed based on method
presented by Cheng,27 known compounds 6 and 7 were prepared based on method presented
by Potter.28
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Phenyl 3,4,6ꢀtriꢀOꢀbenzylꢀ2ꢀOꢀ(oꢀcyanobenzyl)ꢀ1ꢀthioꢀ
βꢀDꢀglucopyranoside (1d, Scheme 1):
Phenyl 2ꢀ ꢀacetylꢀ3,4,6ꢀtriꢀ ꢀbenzylꢀ1ꢀthioꢀ ꢀDꢀglucopyranoside (3 g, 5.1 mmol, 1 equiv.)
O
O
β
was dissolved in CH3OH (15 mL) and KCN (36 mg, 0.5 mmol) was added. The reaction was
stirred for 2 h, and another 36 mg KCN was added. After an additional two hours, TLC
indicated that the reaction was complete, and the mixture was concentrated in vacuo and dry
in high vacuo for 3 h. To the crude oil was added anhydrous MeCN (40 mL) and the solution
was cooled to 0 °C. Sodium hydride (245 mg, 60% dispersion in mineral oil, 6.1 mmol, 1.2
equiv.) was added carefully; the mixture was stirred at 0 °C for 30 minutes. Then
oꢀ
cyanobenzyl bromide (1.21 g, 5.6 mmol, 1.1 equiv.) was added in 3 mL MeCN solution, and
the mixture was allowed to warm to room temperature overnight. The mixture was quenched
with methanol (3 mL). The phases were separated and the aqueous phase was extracted with
ethyl acetate (4
× 20 mL). The combined organic extracts were dried over Na2SO4, filtered
and concentrated in vacuo. Purification of the residue by crystallization from mixture
EtOH/H2O
afforded
phenyl
3,4,6ꢀtriꢀ
O
ꢀbenzylꢀ2ꢀ
O
ꢀ(o
ꢀcyanobenzyl)ꢀ1ꢀthioꢀ
βꢀDꢀ
glucopyranoside (1d) (2.7 g, 78%); mp: 92 – 93 oC; [α]D20 = –15.0 (
c
= 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3) δ 7.68 (d,
J
= 7.8 Hz, 1H), 7.63 (dd,
J
= 7.7, 1.2 Hz, 1H), 7.61 – 7.50 (m,
= 12.5 Hz, 1H), 4.86 (s, 2H),
3H), 7.42 – 7.19 (m, 20H), 5.08 (d,
J
= 12.5 Hz, 1H), 4.99 (d,
J
4.83 (d,
J
= 10.9 Hz, 1H), 4.69 (d,
J = 9.7 Hz, 1H), 4.65 (d, J = 7.3 Hz, 1H), 4.61 (d, J = 12.1
Hz, 1H), 4.54 (d,
J
= 12.1 Hz, 1H), 3.86 – 3.64 (m, 4H), 3.55 (m, 2H); 13C NMR (75 MHz,
CDCl3) δ 141.9, 138.3, 138.2, 138.1, 133. 4, 132.7, 132.6, 132.0, 129.0, 128.6, 128.4, 127.9,
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127.8, 127.7, 127.6, 117.2, 110.9, 87.1, 86.5, 81.1, 79.1, 77.9, 77.2, 75.7, 75.0, 73.4, 72.3,
4
5
6
69.0; HRMS (ESIꢀTOF): calcd. for C41H39NO5S [M
+Na]+: 680.2447, found 680.2433.
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Synthesis of donors 16ꢀ21 have been performed from corresponding alcohols with free
hydroxyl groups at Cꢀ3, Cꢀ4, and Cꢀ6. Synthesis and spectroscopic data for phenyl 2,3,4ꢀtriꢀ
Oꢀbenzylꢀ1ꢀthioꢀ
β
ꢀDꢀglucopyranoside was described by McGarrigle and coꢀworkers.29
ꢀDꢀglucopyranoside have been performed
Synthesis of phenyl 2,3,6ꢀtriꢀOꢀbenzylꢀ1ꢀthioꢀ
β
based on method presented by Møller.30 Phenyl 2,4,6ꢀtriꢀOꢀbenzylꢀ1ꢀthioꢀ
glucopyranoside have been prepared based on method presented by Kanie.31
βꢀDꢀ
General procedures for the preparation of 16, 18 and 20 (Procedure A)
Sugar derivate with free hydroxyl group (1 eq.) and tetrabutylammonium bromide (0.1 eq.)
was dissolved in CH2Cl2 (10 ml). Then was added 33% KOH solution (10 ml) and the
mixture was vigorously stirred at room temperature for 30 minutes. After this time,
oꢀ
nitrobenzyl bromide (1.5 eq.) was added and the reaction was stirred until complete
consumption of starting material (monitored by TLC). Then water (20 ml) was added and the
mixture extracted with CH2Cl2 (3
× 30 mL). The combined organic layer was dried over
Na2SO4, filtered and concentrated in vacuo. Purification of the residue by crystallization from
mixture EtOH/H2O to give corresponding products.
General procedures for the preparation of 17, 19 and 21 (Procedure B)
The starting material (1 eq.) was dissolved in anhydrous MeCN (15 mL) and the solution was
cooled to 0 °C. Sodium hydride (60% dispersion in mineral oil, 2 eq.) was added carefully
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and the mixture was stirred at 0 °C for 1 h. Then
o
ꢀcyanobenzyl bromide (1.5 eq.) was added
4
5
6
7
8
in 1 mL MeCN solution and the mixture was allowed to warm to room temperature overnight.
The mixture was quenched with methanol (1 mL) and the aqueous phase extracted with ethyl
9
acetate (4
× 20 mL). The combined organic extracts were dried over Na2SO4, filtered and
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concentrated in vacuo. Purification of the residue by crystallization from mixture EtOH/H2O
afforded corresponding products.
Phenyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(oꢀnitrobenzyl)ꢀ1ꢀthioꢀβꢀDꢀglucopyranoside (16, Table 4);
Compound 16 was obtained as white solid (490 mg, 55%); mp: 92 – 93 oC; [α]D20 = –3.7 (
1.0, CHCl3); 1H NMR: (600 MHz, CDCl3) δ 8.09 (dd,
c =
J
= 8.2, 1.2 Hz, 1H), 7.85 (dd,
J
= 7.9,
= 8.2, 1.4, 0.7
Hz, 1H), 7.41 – 7.39 (m, 2H), 7.35 – 7.22 (m, 16H), 4.95 – 4.89 (m, 3H), 4.88 – 4.84 (m, 3H),
4.75 (d, = 10.3 Hz, 1H), 4.69 (d, = 9.8 Hz, 1H), 4.62 (d, = 11.1 Hz, 1H), 3.84 (dd,
10.7, 1.9 Hz, 1H), 3.79 (dd,
1.0 Hz, 1H), 7.61 (td,
J = 7.7, 1.2 Hz, 1H), 7.58 – 7.56 (m, 2H), 7.43 (ddd, J
J
J
J
J =
J
= 10.7, 4.7 Hz, 1H), 3.74 (t,
J = 8.9 Hz, 1H), 3.67 (t, J = 9.4 Hz,
1H), 3.56 – 3.52 (m, 1H), 3.53 (dd,
J
= 9.7, 8.7 Hz, 1H); 13C NMR: (151 MHz, CDCl3) δ
146.9, 138.3, 138.0, 137.9, 135.4, 133.8, 133.7, 133.7, 132.0, 128.9, 128.6, 128.5, 128.5,
128.5, 128.4, 128.2, 128.2, 127.9, 127.9, 127.8, 127.5, 124.8, 124.6, 87.4, 86.8, 80.8, 78.8,
77.7, 75.9, 75.4, 75.1, 69.8, 69.8; HRMS (ESIꢀTOF): calcd. for C40H39NO7S [
700.2345, found 700.2329.
M
+Na]+:
Phenyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(oꢀcyanobenzyl)ꢀ1ꢀthioꢀβꢀDꢀglucopyranoside (17, Table 4);
Compound 17 was obtained as white solid (800 mg, 92%); mp: 84 oC; [α]D20 = +1.8 (
CHCl3); 1H NMR: (600 MHz, CDCl3) δ 7.63 (dd,
= 7.7, 0.8 Hz, 1H), 7.59 (dd, J = 7.8, 0.7
c
= 1.0,
J
Hz, 1H), 7.58 – 7.53 (m, 3H), 7.40 – 7.21 (m, 19H), 4.91 (d,
10.3 Hz, 1H), 4.85 (d, = 11.0 Hz, 2H), 4.76 (d, = 13.1 Hz, 1H), 4.74 (d,
4.69 (d, = 9.8 Hz, 1H), 4.69 (d, = 12.6 Hz, 1H), 4.62 (d, = 11.0 Hz, 1H), 3.84 (dd,
10.8, 1.9 Hz, 1H), 3.79 (dd, = 10.8, 4.7 Hz, 1H), 3.72 (t, = 8.9 Hz, 1H), 3.65 (t,
J
= 10.9 Hz, 1H), 4.90 (d,
J =
J
J
J
= 10.3 Hz, 1H),
J
J
J
J =
J
J
J
= 9.4 Hz,
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1H), 3.55 – 3.51 (m, 1H), 3.52 (dd,
J
= 9.7, 8.7 Hz, 1H); 13C NMR: (151 MHz, CDCl3) δ
4
5
6
7
8
142.1, 138.3, 138.0, 137.9, 133.7, 132.8, 132.6, 132.0, 128.9, 128.5, 128.4, 128.3, 128.2,
127.9, 127.9, 127.8, 127.7, 127.4, 117.2, 111.0, 87.4, 86.8, 80.9, 78.9, 77.6, 75.9, 75.4, 75.1,
9
70.9, 69.8; HRMS (ESIꢀTOF): calcd. for C41H39NO5S [M
+Na]+: 680.2447, found 680.2407.
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Phenyl 2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(oꢀnitrobenzyl)ꢀ1ꢀthioꢀβꢀDꢀglucopyranoside (18, Table 4);
Compound 18 was obtained as white solid (720 mg, 78%); mp: 77 oC; [α]D20 = +12.7 (
CHCl3); 1H NMR: (600 MHz, CDCl3) δ 8.03 (dd,
= 8.2, 1.2 Hz, 1H), 7.64 (dd, J = 7.8, 0.9
c
= 1.0,
J
Hz, 1H), 7.60 – 7.57 (m, 2H), 7.52 (td,
(m, 16H), 5.19 (d, = 14.8 Hz, 1H), 4.99 (d,
(d, = 11.1 Hz, 1H), 4.71 (d, = 10.3 Hz, 1H), 4.69 (d,
1H), 4.58 (d, = 11.9 Hz, 1H), 4.51 (d, = 11.8 Hz, 1H), 3.77 (dd, J
J
= 7.7, 1.2 Hz, 1H), 7.40 – 7.37 (m, 3H), 7.34 – 7.13
= 14.8 Hz, 1H), 4.90 (d, = 10.3 Hz, 1H), 4.86
= 9.8 Hz, 1H), 4.66 (d, = 11.1 Hz,
= 10.9, 1.9 Hz, 1H), 3.74
J
J
J
J
J
J
J
J
J
– 3.69 (m, 3H), 3.56 – 3.51 (m, 2H); 13C NMR: (151 MHz, CDCl3) δ 146.8, 138.1, 138.0,
135.0, 133.8, 133.5, 131.9, 128.9, 128.6, 128.4, 128.3, 128.3, 128.2, 127.9, 127.8, 127.7,
127.6, 127.5, 127.5, 124.8, 124.5, 87.5, 86.6, 80.9, 79.0, 78.0, 75.7, 75.4, 73.4, 71.0, 69.1;
HRMS (ESIꢀTOF): calcd. for C40H39NO7S [M
+Na]+: 700.2345, found 700.2338.
Phenyl 2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(oꢀcyanobenzyl)ꢀ1ꢀthioꢀβꢀDꢀglucopyranoside (19, Table 4);
o
20
Compound 19 was obtained as white solid (800 mg, 89%); mp: 86 C; [α]D = –1.4 (c = 1.0,
1
CHCl3); H NMR: (600 MHz, CDCl3) δ 7.60 – 7.57 (m, 3H), 7.45 (td,
J
= 7.7, 1.3 Hz, 1H),
= 11.2 Hz, 1H), 4.90 (d, = 10.3
= 11.2 Hz, 1H), 4.70 (d, = 10.3 Hz, 1H), 4.67
= 11.9 Hz, 1H), 3.81 (d, = 3.2 Hz,
7.38 – 7.21 (m, 20H), 4.97 (d,
Hz, 1H), 4.82 (d, = 12.2 Hz, 1H), 4.78 (d,
(d, = 9.8 Hz, 1H), 4.60 (d,
J
= 12.2 Hz, 1H), 4.91 (d,
J
J
J
J
J
J
J
= 11.9 Hz, 1H), 4.56 (d,
J
J
13
2H), 3.73 – 3.69 (m, 2H), 3.54 – 3.50 (m, 2H); C NMR: (151 MHz, CDCl3) δ 141.6, 138.3,
138.3, 138.0, 133.8, 132.8, 132.0, 128.9, 128.8, 128.4, 128.3, 128.2, 128.0, 127.9, 127.7,
127.6, 127.6, 127.5, 117.4, 111.3, 87.4, 86.5, 80.9, 78.9, 77.9, 75.6, 75.3, 73.3, 72.2, 69.0;
HRMS (ESIꢀTOF): calcd. for C41H39NO5S [M
+Na]+: 680.2447, found 680.2419.
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Phenyl 2,4,6ꢀtriꢀOꢀbenzylꢀ3ꢀOꢀ(oꢀnitrobenzyl)ꢀ1ꢀthioꢀβꢀDꢀglucopyranoside (20, Table 4);
4
5
6
7
8
9
Compound 20 was obtained as white solid (690 mg, 75%); mp: 103 oC; [α]D20 = –7.1 (
CHCl3); 1H NMR: (600 MHz, CDCl3) δ 8.05 (dd,
c
= 1.0,
= 7.8, 0.8
= 7.1 Hz, 1H), 7.37 –
= 15.4 Hz, 1H), 4.89
= 10.9 Hz, 1H), 4.63 (d, = 12.1 Hz,
= 11.0 Hz, 1H), 4.56 (d, = 12.3 Hz, 1H), 3.79 (dd,
= 10.8, 1.9 Hz, 1H), 3.77 – 3.73 (m, 2H), 3.70 (t, = 9.3 Hz, 1H), 3.53 (dd, = 9.7, 8.7 Hz,
J
= 8.2, 1.2 Hz, 1H), 7.84 (dd, J
Hz, 1H), 7.60 – 7.57 (m, 2H), 7.54 (td,
7.18 (m, 16H), 7.09 – 7.07 (m, 2H), 5.25 (d,
(d, = 10.4 Hz, 1H), 4.67 (d, = 9.8 Hz, 1H), 4.65 (d,
1H), 4.58 (d, = 10.8 Hz, 1H), 4.57 (d,
J
= 7.7, 1.2 Hz, 1H), 7.39 (t,
J
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J
= 15.4 Hz, 1H), 5.20 (d,
J
J
J
J
J
J
J
J
J
J
J
1H), 3.51 – 3.48 (m, 1H). 13C NMR: (151 MHz, CDCl3) δ 146.6, 138.2, 137.8, 137.7, 135.6,
133.9, 133.6, 131.9, 128.9, 128.4, 128.3, 128.3, 128.1, 127.8, 127.8, 127.8, 127.7, 127.6,
127.5, 124.6, 87.6, 86.6, 80.9, 79.0, 77.7, 75.4, 74.9, 73.5, 71.5, 68.9. HRMS (ESIꢀTOF):
calcd. for C40H39NO7S [M
+Na]+: 700.2345, found 700.2307.
Phenyl 2,4,6ꢀtriꢀOꢀbenzylꢀ3ꢀOꢀ(oꢀcyanobenzyl)ꢀ1ꢀthioꢀβꢀDꢀglucopyranoside (21, Table 4);
o
Compound 21 was obtained as white solid (1.05 g, 77%); mp: 122 C; [α]D20 = +2.0 (
c
= 1.0,
= 7.8, 1.1 Hz, 1H),
= 7.7, 1.3 Hz, 1H), 7.35 – 7.22 (m, 17H), 7.15 –
= 12.9 Hz, 1H), 5.02 (d, = 12.9 Hz, 1H), 4.91 (d, = 10.4 Hz, 1H),
= 11.0 Hz, 1H), 4.67 (d, = 11.0 Hz, 1H), 4.67 (d, = 9.7 Hz, 1H), 4.60 (d, = 12.0
Hz, 1H), 4.57 (d, = 11.0 Hz, 1H), 4.54 (d, = 12.0 Hz, 1H), 3.77 (dd, = 10.9, 1.9 Hz, 1H),
3.73 – 3.70 (m, 2H), 3.67 (t, = 9.3 Hz, 1H), 3.53 (dd, = 9.7, 8.5 Hz, 1H), 3.51 – 3.48 (m,
CHCl3); 1H NMR: (600 MHz, CDCl3) δ 7.59 – 7.57 (m, 2H), 7.56 (dd,
7.53 (dd, = 7.8, 0.5 Hz, 1H), 7.45 (td,
7.13 (m, 2H), 5.08 (d,
4.72 (d,
J
J
J
J
J
J
J
J
J
J
J
J
J
J
J
1H); 13C NMR: (151 MHz, CDCl3) δ 142.2, 138.2, 137.9, 137.9, 133.9, 132.7, 132.6, 131.9,
128.9, 128.3, 128.1, 127.8, 127.8, 127.7, 127.6, 127.4, 117.2, 110.8, 87.6, 87.0, 80.8, 79.0,
77.7, 75.2, 74.9, 73.4, 72.8, 68.9; HRMS (ESIꢀTOF): calcd. for C41H39NO5S [
680.2447, found 680.2400.
M
+Na]+:
General procedures of glycosylation for compound 2a-d, 4a-d, 8-13, 22-27
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9
o
To cooled solution (ꢀ40 C) of donor (0.076 mmol, 1.0 eq.), Ph2SO (0.084 mmol, 1.1 eq.),
TTBP (0.19 mmol, 2.5 eq.) and freshly activated molecular sieves (3 Å, 100 mg) in 5 ml of
CH2Cl2 was added Tf2O (0.084 mmol, 1.1 eq.). The mixture was allowed to stir at the same
temperature about 15 minutes, next acceptor (0.114 mmol, 1.5 eq.) was added. The mixture
was allowed to warm to RT. After 3 h, 5eq. of Et3N was added and the mixture was stirring
next 15 minutes in RT. The reaction was then quenched with aqueous NH4Cl and extracted
with CH2Cl2. The organic layer was washed with water, dried over MgSO4, and concentrated
in vacuo. The crude product was purified by flash column chromatography on silica gel with
hexane/EtOAc to afford the desired glycosides.
10
11
12
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Methyl 3,4,6ꢀtriꢀOꢀbenzylꢀ2ꢀOꢀ(oꢀcyanobenzyl)ꢀ
α
/
β
ꢀDꢀglucopyranoside (2d, Table 1);
1
Compound 2d was obtained as colorless oil (36 mg; 82%; α/β = 1:12); H NMR (300 MHz,
CDCl3) δ 7.60 (dd,
Hz, 1H), 7.38 – 7.23 (m, 15H), 7.15 (m, 2H), 5.15 (d,
1H), 4.87 (d, = 11.7 Hz, 1H), 4.80 (d, = 11.7 Hz, 1H), 4.79 (d,
J
= 7.8, 0.9 Hz, 1H), 7.54 (dd,
J
= 7.8, 0.9 Hz, 1H), 7.48 (td,
= 12.6 Hz, 1H), 4.88 (d,
= 11.1 Hz, 1H), 4.63 (d, J
J
= 7.6, 1.4
J
J = 12.6 Hz,
J
J
J
= 12.9 Hz, 1H), 4.55 (d,
J = 12.9 Hz, 1H), 4.52 (d, J = 11.1 Hz, 1H), 4.33 (d, J = 7.8 Hz, 1H,
H1ꢀ
β
), 3.80 – 3.59 (m, 4H), 3.57 (s, 3H), 3.51 – 3.40 (m, 2H); 13C NMR (75 MHz, CDCl3) δ
142.2, 138.6, 138.2, 138.1, 132.8, 132.7, 129.1, 128.3, 127.9, 127.8, 127.7, 127.6, 127.5,
117.4, 111.6, 104.4, 84.5, 82.4, 77.9, 77.2, 75.6, 75.0, 74.9, 73.5, 71.7, 68.9, 57.0; HRMS
(ESIꢀTOF): calcd. for C36H37NO6 [
M
+Na]+: 602.2519, found 602.2495.
Methyl
2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(3,4,6ꢀtriꢀOꢀbenzylꢀ2ꢀOꢀ(oꢀcyanobenzyl)ꢀα/βꢀDꢀ
glucopyranosyl)ꢀ
α
ꢀDꢀglucopyranoside (4d, Table 2); Compound 4d was obtained as colorless
oil (66 mg, 86%,
α
/
β = 1:3); 1H NMR (600 MHz, CDCl3) δ 7.54 (m, 1.6H), 7.40 (d,
J = 7.7
Hz, 1.3H), 7.38 – 7.20 (m, 40H), 7.16 (d,
CBn, 0.27H, = 1.8 Hz, H1 ), 4.95 (m, 3.26H), 4.87 – 4.75 (m, 6.1H), 4.71 (d,
Hz, 1H), 4.65 (d,
J = 6.9 Hz, 5H), 5.18 (d, J = 13.2 Hz, 1.27H, HCHꢀ
o
J
’ꢀ
α
J
J
= 10.9
= 10.2
J
= 11.9 Hz, 2H), 4.61 – 4.51 (m, 6H), 4.47 (m, 0.78H), 4.38 (d,
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Hz, 1H), 4.36 (d,
J = 7,8 Hz, 1H, H1’ꢀβ) 4.16 (d, J = 10.7 Hz, 1H), 3.96 (m, 1.74H), 3.87 (m,
4
5
6
7
8
0.3H), 3.82 – 3.62 (m, 7.45H), 3.62 – 3.55 (m, 2.85H), 3.51 (m, 1.24H), 3.46 – 3.41 (m,
1.2H), 3.41 – 3.37 (m, 6H), 3.35 (s, 0.8H), 3.32 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 142.2,
139.0, 138.5, 138.4, 138.3, 138.2, 138.1, 132.9, 132.7, 132.6, 132.4, 128.4, 128.3, 128.2,
128.1, 128.00, 127.9, 127.8, 127.7, 127.6, 127.5, 117.2, 117.1, 110.8, 110.6, 103.6, 98.1, 97.9,
96.9, 84.6, 82.2, 82.1, 81.9, 81.5, 80.3, 80.0, 78.1, 77.9, 77.7, 75.7, 75.6, 75.4, 75.1, 74.9,
74.7, 73.5, 73.4, 73.1, 71.7, 70.4, 69.7, 69.3, 69.0, 68.6, 68.5, 65.8, 55.2; HRMS (ESIꢀTOF):
9
10
11
12
13
14
15
16
17
18
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21
22
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26
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59
60
calcd. for C63H65NO11 [
M
+Na]+: 1034.4450, found 1034.4438.
Methyl
2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(3,4,6ꢀtriꢀOꢀbenzylꢀ2ꢀOꢀ(oꢀcyanobenzyl)ꢀα/βꢀDꢀ
glucopyranosyl)ꢀ
(52 mg, 67%,
α
ꢀDꢀglucopyranoside (8, Table 3); Compound 8 was obtained as colorless oil
1
α/
β = 1:5); H NMR (500 MHz, CDCl3) δ 7.63 – 7.58 (m, 0.2H), 7.57 – 7.55
(m, 1.2H), 7.54 – 7.46 (m, 3H), 7.44 – 7.40 (m, 3H), 7.39 – 7.26 (m, 42H), 7.18 – 7.11 (m,
3H), 5.16 (d, = 12.8 Hz, 1H), 5.08 (d, = 3.7 Hz, 0.2H, H1’ꢀ ), 4.99 – 4.91 (m, 3.8H), 4.87
– 4.79 (m, 7.2H), 4.78 (d, = 2.1 Hz, 1.2H, H1ꢀ ), 4.68 (d, = 6.5 Hz, 1H, H1’ꢀ ), 4.67 –
4.60 (m, 4.7H), 4.60 – 4.54 (m, 3H), 4.54 – 4.44 (m, 5H), 4.06 (t, = 9.4 Hz, 0.2H), 3.98 (t,
J
J
α
J
α
J
β
J
J
= 9.3 Hz, 1H), 3.85 – 3.68 (m, 6H), 3.66 – 3.50 (m, 7.8H), 3.49 – 3.42 (m, 2H), 3.40 (s,
0.6H), 3.37 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 143.6, 140.2, 139.9, 139.7, 139.6, 139.5,
139.3, 138.7, 138.0, 135.0, 134.1, 134.0, 132.8, 130.8, 130.3, 130.2, 129.9, 129.8, 129.6,
129.4, 129.3, 129.2, 129.1, 129.0, 118.8, 112.7, 103.6, 99.6, 97.1, 85.9, 83.83, 83.6, 82.0,
81.3, 79.4, 79.1, 79.0, 78.7, 78.4, 78.2, 77.2, 77.0, 76.4, 76.3, 74.9, 74.8, 73.2, 72.5, 72.0,
71.7, 71.5, 70.3, 69.9, 61.8, 56.6; HRMS (ESIꢀTOF): calcd. for C63H65NO11
[
M
+Na]+:1034.4450, found 1034.4435.
Methyl 4,6ꢀOꢀbenzylideneꢀ3ꢀOꢀbenzylꢀ2ꢀOꢀ(3,4,6ꢀtriꢀOꢀbenzylꢀ2ꢀOꢀ(oꢀcyanobenzyl)ꢀ
glucopyranosyl)ꢀ ꢀDꢀglucopyranoside (9, Table 3); Compound 9 was obtained as colorless oil
(24 mg, 34%,
α/βꢀDꢀ
α
1
α/
β = 1:5); H NMR (600 MHz, CDCl3) δ 7.72 – 7.67 (m, 0.5H), 7.56 – 7.47
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(m, 5H), 7.39 – 7.18 (m, 39H), 7.17 – 7.12 (m, 2.6H), 5.59 (s, 0.16H), 5.55 (s, 1H), 5.19 (d,
J
4
5
6
7
8
= 13.0 Hz, 1H), 5.13 (d,
– 4.48 (m, 6.5H), 4.43 (dd,
1.5H), 3.96 – 3.84 (m, 2.3H), 3.80 – 3.72 (m, 2H), 3.73 – 3.63 (m, 6H), 3.61 (d,
J
= 12.7 Hz, 0.2H), 5.02 – 4.76 (m, 8H), 4.70 – 4.67 (m, 0.5H), 4.61
= 9.4, 3.8 Hz, 0.2H), 4.33 – 4.30 (m, 1.1H), 4.11 – 4.06 (m,
= 8.5 Hz,
J
9
J
10
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60
0.8H), 3.60 – 3.52 (m, 2H), 3.55 – 3.45 (m, 1.5H), 3.44 (s, 4.2H), 3.38 (s, 0.5H); 13C NMR
(151 MHz, CDCl3) δ 145.7, 142.3, 138.5, 138.0, 137.4, 132.7, 132.6, 132.5, 132.4, 131.1,
129.3, 129.0, 128.9, 128.8, 128.4, 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6,
127.5, 127.4, 126.0, 125.0, 124.8, 123.4, 117.4, 111.07, 104.1, 101.4, 100.4, 84.5, 84.4, 82.9,
82.3, 82.2, 78.5, 78.0, 77.9, 77.8, 77.2, 77.0, 76.8, 75.6, 75.5, 75.1, 75.0, 74.9, 74.7, 73.4,
73.3, 71.7, 69.2, 69.0, 62.2, 60.4, 55.4; HRMS (ESIꢀTOF): calcd. for C56H57NO11
942.3824, found 942.3791.
[M
+Na]+:
Methyl
4,6ꢀOꢀbenzylideneꢀ2ꢀOꢀbenzylꢀ3ꢀOꢀ(3,4,6ꢀtriꢀOꢀbenzylꢀ2ꢀOꢀ(oꢀcyanobenzyl)ꢀα/βꢀDꢀ
glucopyranosyl)ꢀα/βꢀDꢀglucopyranoside (10, Table 3); Compound 10 was obtained as
1
colorless oil (50 mg, 72%,
α/β
= 1:4); H NMR (600 MHz, CDCl3) δ 7.58 – 7.55 (m, 2H),
7.51 – 7.48 (m, 3H), 7.46 – 7.41 (m, 2H), 7.40 – 7.26 (m, 37H), 7.18 – 7.10 (m, 2.4H), 5.55
(s, 1H), 5.16 (d, = 12.7 Hz, 1H), 5.08 (d, = 3.6 Hz, 0.25H, H1’ꢀ ), 5.05 – 5.02 (m, 0.25H),
4.98 – 4.90 (m, 3H), 4.88 – 4.76 (m, 6H), 4.76 – 4.60 (m, 4.2H), 4.59 (d,
H1ꢀ ), 4.58 – 4.54 (m, 1.6H), 4.52 (d, = 7.8 Hz, 1H, H1’ꢀ ), 4.49 (dd,
1H), 4.27 (dd,
J
J
α
J
= 3.7 Hz, 1.2H,
α
J
β
J = 11.4, 5.7 Hz,
J
= 10.2, 4.8 Hz, 1H), 4.08 – 4.02 (m, 1.4H), 3.85 – 3.80 (m, 2.6H), 3.78 – 3.69
(m, 3.4H), 3.65 – 3.58 (m, 3.2H), 3.58 – 3.52 (m, 1.8H), 3.51 – 3.46 (m, 1.3H), 3.41 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 142.2, 138.7, 138.5, 138.1, 137.4, 137.2, 136.60, 133.6, 132.8,
132.7, 132.6, 131.4, 129.7, 129.4, 129.0, 128.9, 128.8, 128.7, 128.5, 128.4, 128.3, 128.2,
128.1, 128.0, 127.9, 127.8, 127.6, 126.0, 117.4, 117.1, 111.5, 111.2, 102.1, 101.3, 99.2, 95.7,
84.5, 82.4, 82.1, 81.9, 81.3, 80.5, 79.8, 79.1, 78.6, 77.9, 77.9, 77.6, 75.6, 75.3, 75.1, 75.0,
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74.9, 73.8, 73.5, 73.1, 71.8, 71.1, 70.6, 70.5, 70.3, 69.6, 69.1, 68.8, 68.3, 62.3, 55.3; HRMS
4
5
6
7
(ESIꢀTOF): calcd. for C56H57NO11 [
M
+Na]+: 942.3824, found 942.3807.
ꢀDꢀglucopyranoside (11, Table 3);
Isopropyl 3,4,6ꢀtriꢀOꢀbenzylꢀ2ꢀOꢀ(oꢀcyanobenzyl)ꢀ
β
8
9
o
20
Compound 11 was obtained as solid (36 mg, 78%); mp: 63 – 65 C; [α]D = –9.5 (
c = 0.5,
10
11
12
13
14
15
16
17
18
19
20
21
22
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34
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36
37
38
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41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
CHCl3); 1H NMR (500 MHz, CDCl3) δ 7.58 – 7.55 (m, 1H), 7.50 – 7.41 (m, 2H), 7.36 – 7.25
(m, 17H), 7.19 – 7.15 (m, 2H), 5.20 (d,
= 12.0 Hz, 1H), 4.81 (d, = 12.0 Hz, 1H), 4.80 (d,
1H), 4.57 (dd, = 12.2, 1H), 4.54 (d, = 12.0, 1H), 4.49 (d,
(hept, = 6.1 Hz, 1H), 3.73 (dd,
3.57 (t, = 9.3 Hz, 1H), 3.50 – 3.38 (m, 2H), 1.30 (d,
J
= 12.9 Hz, 1H), 4.93 (d,
J = 12.9 Hz, 1H), 4.87 (d, J
J
J
= 12.0 Hz, 1H), 4.61 (d,
J
= 12.2 Hz,
J
J
J
= 7.8 Hz, 1H, H1ꢀβ), 4.03
J
J
= 10.8, 2.0 Hz, 1H), 3.66 (m, 1H), 3.67 (t,
J
= 9.3 Hz, 1H),
= 6.1 Hz,
J
J
= 6.2 Hz, 3H), 1.21 (d, J
3H); 13C NMR (126 MHz, CDCl3) δ 142.4, 138.6, 138.3, 138.1, 136.6, 132.7, 129.4, 128.9,
128.8, 128.4, 128.3, 128.0, 127.8, 127.7, 127.6, 127.5, 117.4, 111.2, 101.8, 84.6, 82.4, 78.1,
75.6, 75.0, 74.8, 73.5, 72.2, 71.6, 69.1, 23.7, 22.0; HRMS (ESIꢀTOF): calcd. for C38H41NO6
[
M
+Na]+: 630.2826, found 630.2796.
Benzyl 3,4,6ꢀtriꢀOꢀbenzylꢀ2ꢀOꢀ(oꢀcyanobenzyl)ꢀ
α/β
ꢀDꢀglucopyranoside (12, Table 3);
1
Compound 12 was obtained as colorless oil (33 mg, 67%,
α/β
= 1:10); H NMR (500 MHz,
CDCl3) δ 1H NMR (500 MHz, CDCl3) δ 7.63 – 7.55 (m, 1.86H), 7.52 – 7.48 (m, 1H), 7.45 –
7.27 (m, 24H), 7.18 – 7.15 (m, 2H), 5.17 (d, = 12.7 Hz, 1H), 5.08 (d, = 3.7 Hz, 0.18H),
4.98 – 4.91 (m, 2.32H), 4.88 – 4.72 (m, 4H), 4.71 – 4.60 (m, 3H), 4.60 – 4.54 (m, 1.73H),
J
J
4.53 (d,
J
= 7.8 Hz, 1.65H), 4.49 (dd,
J
= 11.4, 3.7 Hz, 0.58H), 4.09 – 4.03 (m, 0.2H), 3.82 –
13
3.50 (m, 6.41H), 3.49 – 3.45 (m, 1.13H); C NMR (126 MHz, CDCl3) δ 142.2, 138.5, 138.2,
138.1, 137.3, 136.6, 133.63, 132.8, 132.7, 132.6, 131.4, 129.5, 128.9, 128.8, 128.8, 128.6,
128.4, 128.3, 128.2, 128.1, 127.9, 127.8, 127.6, 117.4, 111.3, 102.2, 95.7, 84.5, 82.4, 80.0,
80.6, 78.0, 77.6, 77.3, 77.0, 76.8, 75.6, 75.1, 75.0, 74.9, 73.5, 71.8, 71.1, 70.5, 70.3, 69.6,
68.9, 68.3; HRMS (ESIꢀTOF): calcd. for C42H41NO6 [M
+Na]+: 678.2826, found 678.2799.
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Nonyl 3,4,6ꢀtriꢀOꢀbenzylꢀ2ꢀOꢀ(oꢀcyanobenzyl)ꢀ
β
ꢀDꢀglucopyranoside (13, Table 3); Compound
13 was obtained as colorless oil (28 mg, 54%); [α]D20 = –2.8 ( = 0.5, CHCl3); 1H NMR (600
c
7
8
9
MHz, CDCl3) δ 7.60 – 7.56 (m, 1H), 7.48 (ddd,
7.30 – 7.23 (m, 10H), 7.18 – 7.14 (m, 2H), 5.18 (d,
1H), 4.87 (d, = 11.1 Hz, 1H), 4.81 (d, = 10.8, 1H), 4.79 (d,
Hz, 1H), 4.56 (d, = 12.2 Hz, 1H), 4.54 (d, = 10.8 Hz, 1H), 4.41 (d,
3.93 (dt, = 9.4, 6.7 Hz, 1H), 3.75 (dd, = 10.8, 1.9 Hz, 1H), 3.71 – 3.62 (m, 2H), 3.59 (t,
9.3 Hz, 1H), 3.54 (dt,
1.16 (m, 12H), 0.87 (t,
J
= 7.7, 6.4, 1.2 Hz, 1H), 7.36 – 7.30 (m, 4H),
= 12.8 Hz, 1H), 4.92 (d, = 12.8 Hz,
= 11.1, 1H), 4.62 (d, = 12.2
= 7.8 Hz, 1H, H1ꢀ
J
J
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
J
J
J
J
J
J
J
β
),
=
J
J
J
J
= 9.4, 6.9 Hz, 1H), 3.50 – 3.42 (m, 2H), 1.67 – 1.60 (m, 2H), 1.38 –
= 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3) δ 142.4, 138.6, 138.2,
J
138.1, 132.7, 132.6, 128.8, 128.4, 128.3, 128.0, 127.7, 127.6, 127.5, 117.3, 111.3, 103.4, 84.5,
82.4, 78.1, 75.6, 75.0, 74.9, 73.5, 71.6, 70.2, 69.0, 31.9, 29.7, 29.5, 29.4, 29.3, 26.1, 22.7,
14.1
;
HRMS (ESIꢀTOF): calcd. for C44H53NO6 [
M
+Na]+: 714.3765, found 714.3742.
Methyl
2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(oꢀnitrobenzyl)ꢀα/βꢀDꢀ
glucopyranosyl)ꢀα/βꢀDꢀglucopyranoside (22, Table 4); Compound 22 was obtained as
β = 2:1); 1H NMR: (300 MHz, CDCl3) δ 8.06 – 8.02 (m, 1.7H),
colorless oil (57 mg, 73%, α/
7.81 (dd, J = 7.8, 1.0 Hz, 0.7H), 7.75 (dd, J = 7.8, 1.1 Hz, 1.2H), 7.60 – 7.52 (m, 2.3H), 7.42 –
7.13 (m, 55H), 5.01 – 4.48 (m, 27.5H), 4.37 (d,
J = 7.7 Hz, 0.6H), 4.17 – 4.07 (m, 1.6H), 3.99
(td,
J
= 9.3, 2.6 Hz, 2.7H), 3.87 – 3.41 (m, 18H), 3.36 (s, 3H), 3.33 (s, 1.7H); 13C NMR: (75
MHz, CDCl3) δ 146.9, 146.8, 138.8, 138.6, 138.4, 138.2, 138.1, 138.0, 135.3, 135.2, 133.7,
128.3, 128.1, 128.0, 127.9, 127.8, 127.7, 127.6, 124.5, 103.8, 98.1, 98.0, 97.1, 84.8, 82.1,
82.0, 81.7, 80.1, 79.8, 77.8, 75.8, 75.7, 75.6, 74.9, 73.3, 72.4, 70.4, 70.2, 69.9, 69.7, 66.1,
55.2, 55.2; HRMS (ESIꢀTOF): calcd. for C62H65NO13 [
M
+Na]+: 1054.4354, found 1054.4336.
Methyl 2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(oꢀcyanobenzyl)ꢀα/βꢀDꢀ
glucopyranosyl)ꢀα/βꢀDꢀglucopyranoside (23, Table 4); Compound 23 was obtained as
1
colorless oil (65 mg, 85%,
α/
β = 2:1); H NMR: (600 MHz, CDCl3) δ 7.61 – 7.48 (m, 7H),
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5
6
7
8
9
7.46 (dd,
11.5 Hz, 0.3H), 5.00 – 4.53 (m, 28H), 4.51 (d,
4.37 (d, = 7.8 Hz, 0.4H, H1ꢀβ), 4.20 – 4.16 (m, 0.7H), 4.13 – 4.10 (m, 0.6H), 3.98 (td,
9.3, 4.2 Hz, 2.5H), 3.85 – 3.47 (m, 17H), 3.44 (dd,
J
= 7.7, 1.3 Hz, 0.3H), 7.35 – 7.15 (m, 59H), 5.18 (d,
J
= 3.4 Hz, 0.3H), 5.12 (d,
J
=
=
J
= 11.2 Hz, 0.4H), 4.47 (d,
J
= 13.1 Hz, 0.3H),
J
J
J
= 9.6, 3.6 Hz, 1H), 3.36 (s, 3H), 3.32 (s,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1.3H); 13C NMR: (151 MHz, CDCl3) δ 142.0, 138.8, 138.7, 138.4, 138.2, 138.0, 133.1, 133.0,
132.8, 132.5, 129.3, 128.4, 128.4, 128.3, 128.3, 128.2, 128.1, 128.1, 128.0, 127.8, 127.7,
127.7, 127.6, 127.5, 117.2, 110.9, 103.8, 98.1, 98.0, 97.2, 82.1, 82.0, 81.7, 80.2, 80.1, 79.8,
77.8, 77.7, 77.5, 77.4, 75.7, 75.6, 75.5, 75.0, 74.9, 74.9, 73.3, 73.2, 72.4, 70.9, 70.7, 70.4,
70.3, 69.9, 69.5, 66.1, 55.2, 55.2; HRMS (ESIꢀTOF): calcd. for C63H65NO11
1034.4455, found 1034.4410.
[M
+Na]+:
Methyl
2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(oꢀnitrobenzyl)ꢀα/βꢀDꢀ
glucopyranosyl)ꢀα/βꢀDꢀglucopyranoside (24, Table 4); Compound 24 was obtained as white
1
solid (62 mg, 79%,
0.3H), 8.02 (dd,
7.51 (td, = 7.7, 1.2 Hz, 1.3H), 7.46 (td,
7.38 (t,
0.3H), 5.17 (d,
= 7.8 Hz, 1H, H1ꢀβ), 4.18 (dd,
α
/
β = 1:3); H NMR: (600 MHz, CDCl3) δ 8.07 (dd,
J
= 8.1, 1.2 Hz,
J
= 8.2, 1.2 Hz, 1.2H), 7.62 (d,
J
= 7.8 Hz, 1H), 7.54 (d,
J
J
= 7.8 Hz, 0.7H),
= 7.7 Hz, 0.4H),
J
J
= 7.7, 1.3 Hz, 0.5H), 7.42 (t,
J
= 7.8 Hz, 1.8H), 7.34 – 7.14 (m, 44H), 7.12 – 7.09 (m, 2H), 5.19 (d,
= 14.8 Hz, 1H), 4.99 – 4.48 (m, 21H), 4.39 (d, = 12.1 Hz, 0.3H), 4.36 (d,
J = 14.9 Hz,
J
J
J
J
= 10.9, 2.0 Hz, 1H), 3.99 (t,
J
= 9.3 Hz, 1H), 3.94 (t,
J
= 9.3
13
Hz, 0.3H), 3.86 – 3.43 (m, 15H), 3.37 (s, 1H), 3.33 (s, 3H); C NMR: (151 MHz, CDCl3) δ
146.8, 146.7, 138.8, 138.8, 138.5, 138.4, 138.4, 138.3, 138.2, 138.2, 138.1, 138.1, 135.1,
134.9, 133.8, 133.5, 133.4, 128.6, 128.5, 128.4, 128.3, 128.2, 128.2, 128.1, 128.0, 127.9,
127.9, 127.8, 127.7, 127.7, 127.6, 127.6, 127.5, 127.4, 124.6, 124.5, 124.4, 104.3, 103.8, 98.1,
98.0, 84.6, 82.2, 82.1, 82.0, 81.4, 80.0, 79.8, 78.1, 78.0, 77.8, 77.7, 76.2, 75.7, 75.7, 75.5,
74.9, 74.8, 74.1, 73.4, 73.3, 72.4, 71.9, 70.9, 70.3, 70.1, 69.9, 69.3, 69.1, 68.6, 66.2, 65.4,
55.2, 55.1; HRMS (ESIꢀTOF): calcd. for C62H65NO13 [
M
+Na]+: 1054.4354, found 1054.4310.
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2
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Methyl
2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2,3,6ꢀtriꢀOꢀbenzylꢀ4ꢀOꢀ(oꢀcyanobenzyl)ꢀα/βꢀDꢀ
4
5
6
glucopyranosyl)ꢀα/βꢀDꢀglucopyranoside (25, Table 4); Compound 25 was obtained as white
7
8
1
solid (72 mg, 93%,
α/
β = 1:2); H NMR: (600 MHz, CDCl3) δ 7.59 – 7.56 (m, 1.7H), 7.47 –
9
7.40 (m, 3.3H), 7.35 – 7.17 (m, 55H), 4.99 – 4.90 (m, 7H), 4.82 – 4.45 (m, 19H), 4.35 (d,
7.8 Hz, 1H), 4.17 (dd, = 10.9, 2.0 Hz, 1H), 4.01 – 3.93 (m, 2.3H), 3.85 – 3.41 (m, 17.3H),
J =
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
J
3.36 (s, 1.7H), 3.32 (s, 3H); 13C NMR: (151 MHz, CDCl3) δ 142.1, 141.7, 138.9, 138.7,
138.5, 138.4, 138.3, 138.2, 138.1, 138.0, 132.7, 132.7, 132.6, 132.6, 131.0, 129.3, 128.8,
128.6, 128.4, 128.4, 128.4, 128.3, 128.3, 128.2, 128.1, 128.0, 127.9, 127.9, 127.8, 127.8,
127.7, 127.7, 127.6, 127.6, 127.5, 127.5, 127.4, 127.4, 124.8, 117.4, 111.4, 103.8, 98.0, 98.0,
97.2, 84.5, 82.2, 82.0, 80.2, 80.1, 79.8, 78.1, 78.0, 77.8, 75.7, 75.6, 75.4, 75.3, 74.9, 74.8,
74.8, 73.3, 72.3, 72.1, 70.4, 70.1, 69.9, 69.0, 68.6, 66.1, 55.2, 55.1; HRMS (ESIꢀTOF): calcd.
for C63H65NO11 [
M
+Na]+: 1034.4455, found 1034.4427.
Methyl
2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2,4,6ꢀtriꢀOꢀbenzylꢀ3ꢀOꢀ(oꢀnitrobenzyl)ꢀα/βꢀDꢀ
glucopyranosyl)ꢀα/βꢀDꢀglucopyranoside (26 Table 4); Compound 26 was obtained as white
β = 1:1); 1H NMR: (600 MHz, CDCl3) δ 8.05 (dd,
solid (77 mg, 98%,
α/
J = 8.2, 1.2 Hz, 1H),
8.05 (dd,
(dd, = 8.0, 1.6 Hz, 1H), 7.58 – 7.55 (m, 2H), 7.55 – 7.52 (m, 1H), 7.45 (d,
7.41 – 7.19 (m, 70H), 7.17 – 7.15 (m, 2H), 5.25 (d, = 3.6 Hz, 1H), 5.02 (d,
5.00 – 4.84 (m, 12H), 4.82 – 4.75 (m, 7H), 4.74 – 4.63 (m, 8H), 4.61 – 4.56 (m, 5H), 4.50 (d,
= 11.2 Hz, 1H), 4.37 (d, = 7.8 Hz, 1H), 4.23 – 4.20 (m, 1H), 4.18 (dd, = 10.9, 2.0 Hz,
J
= 8.2, 1.2 Hz, 1H), 7.81 (dd,
J
= 7.8, 0.8 Hz, 1H), 7.74 (t,
J
= 7.9 Hz, 2H), 7.65
= 7.5 Hz, 1H),
= 10.7 Hz, 1H),
J
J
J
J
J
J
J
1H), 4.08 (t,
J
= 9.3 Hz, 1H), 4.01 – 3.96 (m, 2H), 3.85 – 3.58 (m, 16H), 3.56 – 3.49 (m, 4H),
13
3.47 – 3.42 (m, 2H), 3.36 (s, 3H), 3.33 (s, 3H). C NMR: (151 MHz, CDCl3) δ 146.9, 138.8,
138.7, 138.4, 138.2, 138.1, 138.0, 135.3, 135.2, 135.1, 133.7, 131.0, 129.3, 128.5, 128.4,
128.4, 128.4, 128.3, 128.2, 128.1, 128.0, 128.0, 127.9, 127.8, 127.7, 127.7, 127.7, 127.6,
127.6, 127.5, 127.4, 124.8, 124.6, 124.5, 103.8, 98.1, 98.0, 97.1, 84.8, 82.1, 82.1, 82.0, 81.9,
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81.8, 81.7, 80.2, 80.1, 79.8, 79.6, 78.0, 77.8, 77.7, 77.6, 75.8, 75.8, 75.7, 75.6, 75.6, 75.1,
75.0, 75.0, 74.9, 74.9, 74.8, 73.3, 73.3, 72.9, 72.4, 70.7, 70.4, 70.2, 69.9, 69.8, 69.7, 69.7,
6
7
8
9
69.3, 68.5, 66.1, 55.2, 55.2; HRMS (ESIꢀTOF): calcd. for C62H65NO13
found 1054.4320.
[M
+Na]+: 1054.4354,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Methyl
2,3,4ꢀtriꢀOꢀbenzylꢀ6ꢀOꢀ(2,4,6ꢀtriꢀOꢀbenzylꢀ3ꢀOꢀ(oꢀcyanobenzyl)ꢀα/βꢀDꢀ
glucopyranosyl)ꢀα/βꢀDꢀglucopyranoside (27, Table 4); Compound 27 was obtained as white
1
solid (62 mg, 80%,
7.44 (m, 1H), 7.42 (td,
70H), 5.13 (d, = 12.8 Hz, 1H), 5.09 (d,
11.2 Hz, 1H), 4.82 – 4.49 (m, 22H), 4.45 (d,
α/
β = 1:1); H NMR: (600 MHz, CDCl3) δ 7.57 – 7.49 (m, 5H), 7.46 –
J
= 7.7, 1.3 Hz, 1H), 7.39 (td,
= 13.0 Hz, 1H), 5.01 – 4.95 (m, 6H), 4.92 (d,
= 11.1 Hz, 1H), 4.42 (d, = 12.1 Hz, 1H), 4.35
J = 7.8, 1.3 Hz, 1H), 7.35 – 7.09 (m,
J
J
J =
J
J
(d,
J
= 7.8 Hz, 1H, H1ꢀβ), 4.17 (dd,
J = 10.9, 2.0 Hz, 1H), 4.01 – 3.93 (m, 3H), 3.85 – 3.79
(m, 2H), 3.77 (dd,
J
= 10.9, 2.9 Hz, 2H), 3.70 – 3.40 (m, 18H), 3.35 (s, 3H), 3.32 (s, 3H); 13C
NMR: (151 MHz, CDCl3) δ 142.6, 142.4, 138.8, 138.8, 138.4, 138.3, 138.2, 138.2, 138.1,
137.9, 137.9, 132.7, 132.6, 132.5, 132.5, 128.7, 128.4, 128.4, 128.4, 128.3, 128.3, 128.2,
128.1, 128.0, 127.9, 127.9, 127.8, 127.7, 127.6, 127.6, 127.5, 127.4, 117.3, 117.2, 111.0,
110.6, 103.8, 98.0, 98.0, 97.0, 85.1, 82.1, 81.9, 81.7, 80.1, 79.8, 78.1, 77.7, 77.5, 77.4, 75.6,
74.9, 74.9, 74.8, 74.8, 74.6, 73.4, 73.4, 73.3, 72.5, 72.4, 72.1, 70.3, 70.1, 69.9, 68.9, 68.6,
68.4, 66.1, 55.2, 55.1; HRMS (ESIꢀTOF): calcd. for C63H65NO11 [
1034.4419.
M
+Na]+: 1034.4455, found
Acknowledgements: Project operated within the Foundation for Polish Science TEAM
Programmes coꢀfinanced by the EU European Regional Development Fund. Financial support
from the Polish National Science Centre (Grant Nr. 2012/05/B/ST5/00275) is gratefully
acknowledged. The research was carried out with the equipment purchased thanks to the
financial support of the European Regional Development Fund in the framework of the Polish
Innovation Economy Operational Program (contract no. POIG.02.01.00ꢀ12ꢀ023/08).
Computational study was supported in part by the PLꢀGrid Infrastructure.
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