Unexpected anomeric selectivity of a 1-C-arylglycal donor in Kdo glycoside synthesis

Article abstract of DOI:10.1021/jo201531j

A novel class of 1-C-arylglycals was developed and subjected to N-iodosuccinimide-mediated glycosylations with alcohols. Unexpectedly, all reactions provided 2-iodo-β-d-ketopyranosides in high yields and excellent stereoselectivity. After removal of the 2-iodide by radical conditions, the aryl group was smoothly oxidized to provide the corresponding β-Kdo glycosides. A mechanism for the stereoselective formation of β-d-ketopyranosides was proposed, which was supported by evidence from X-ray crystallography.

Full text of DOI:10.1021/jo201531j

Article
pubs.acs.org/joc
Unexpected Anomeric Selectivity of a 1-C-Arylglycal Donor in Kdo
Glycoside Synthesis
Yuxin Qian, Jianhao Feng, Masood Parvez, and Chang-Chun Ling*
Alberta Ingenuity Centre for Carbohydrate Science, Department of Chemistry, University of Calgary, 2500 University Drive NW,
Calgary, Alberta T3G 3M9, Canada.
S
* Supporting Information
ABSTRACT: A novel class of 1-C-arylglycals was developed and subjected to N-iodosuccinimide-mediated glycosylations with
alcohols. Unexpectedly, all reactions provided 2-iodo-β-D-ketopyranosides in high yields and excellent stereoselectivity. After
removal of the 2-iodide by radical conditions, the aryl group was smoothly oxidized to provide the corresponding β-Kdo
glycosides. A mechanism for the stereoselective formation of β-D-ketopyranosides was proposed, which was supported by
evidence from X-ray crystallography.
of the α,β-unsaturated ester−Kdo glycals such as 3 (Figure 1),
which are formed via a concomitant elimination. Previous work
has shown that the use of either glycosyl halides13−17 or
thioglycoside18 suffered similar problems. This side reaction is
extremely wasteful as Kdo monosaccharide is not commercially
available, and it is usually chemically synthesized in low yield
from the condensation of D-arabinose and oxalacetic acid
followed by a nickel-catalyzed decarboxylation.19,20 The
conversion of it to useful donors still requires multistep
transformations. Kosma et al. probed the reactivity of
peracetylated Kdo glycals. For example, they reacted the
peracetylated glycal 3 (R = Me, Figure 1) with acetic acid using
N-iodosuccinimide (NIS) as an activator21 and found that
compound 3 was relatively unreactive, as the reaction needs to
be carried out at 60 °C for 15 h to afford the corresponding α-
anomer in 71% yield. The NIS-mediated glycosylation
preferred a trans-diaxial addition. In their later work, the
same group reported another example of iodoacetoxylation
using a peracetylated α(2,8)-linked Kdo disaccharide glycal as a
substrate,22 and they showed that the more complex glycal
could also react with acetic acid in a similar manner, but at
milder conditions (ambient temperature) to furnish the
corresponding trans-diaxial adduct in 77% yield. More recent
work from Oscarson’s group18 showed that glycal 3 could react
with 2-(4-trifluoroacetamidophenyl)ethanol in a similar addi-
tion pattern under the activation of NIS/triflic acid (TfOH) to
afford the corresponding α-Kdo glycoside in 53% yield;
however, the glycosylation required the use of 4 equiv of
TfOH as an activator. Tanaka et al. prepared a more activated
glycal which had all the acetyl groups in 3 replaced with benzyl
INTRODUCTION
■
Kdo, or 3-deoxy-D-manno-oct-2-ulosonic acid, is an 8-carbon
monosaccharide invariably expressed by Gram-negative bacteria
which produce characteristic lipopolysaccharides (LPS).1−4
The negatively charged polysaccharides play a vital role in
protecting the structural integrity of the cell membranes against
external chemical attack. Kdo is an essential component found
at the inner core part of the LPS. Although Kdo glycosides exist
as the α-anomer in the majority of the LPS structures (1, Figure
Figure 1. Structures of naturally occurring Kdo glycosides and Kdo-
glycals (3).
1), β-anomeric form has been discovered in Alteromonas
macleodii ATCC 27126, which is a Gram-negative bacterium.5
In Gram-positive bacteria, both α- and β-Kdo glycosides6−8 are
found in their capsular polysaccharides. The cytidine 5′-
phosphate Kdo (CMP-Kdo, 2)9−11 is the key intermediate
used by different Kdo transferases to synthesize natural Kdo
glycosides.
Because of the 3-deoxy functionality as well as the presence
of an electron-withdrawing carboxylate at C-1, the chemical
synthesis of Kdo glycosides is often hampered by the poor
stereocontrol of the anomeric configuration,6,12,13 and the
glycosylation efficiency is commonly hindered by the formation
Received: July 28, 2011
Published: December 5, 2011
© 2011 American Chemical Society
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groups;23 this resulted in a more reactive glycal donor because
of the electron-donating effect of benzyl groups. Their results
showed that the NIS-mediated glycosylations still required a
stoichiometric amount of triflic acid to afford the corresponding
α-Kdo glycosides in excellent yields and high stereoselectivity.
In this work, we report the development of a novel class of
3,4;6,7-di-O-isopropylidenated glycals containing a 1-C-aryl
substituent which showed unexpected β-anomeric selectivity
when subjected to NIS-mediated glycosylations, and the
oxidation of the 1-C-aryl group led to the formation of β-
Kdo glycosides.
mixture. We also carried out our independent studies by
reacting 6 with 1.5 equiv of NIS in acetonitrile; the reaction
afforded a major compound which was isolated in 59% by
column chromatography. After a tri-n-butyltin hydride-medi-
ated radical deiodination, the deoxy compound was obtained
and characterized as the furanoside 927 in 83%. The coupling
patterns (doublet of doublets) of the two protons attached to
the deoxygenated carbon were consistent with the proposed
structure. This established that the NIS-mediated ring closure
favored the formation of a five-membered ring (compounds 8),
rather than the most desired six-membered ring found in 5. We
attempted to vary reaction conditions by carrying out ring
closure at either low or high temperatures or by changing the
reaction media to less polar solvents such as dichloromethane;
however, all attempts were unsuccessful.
RESULTS AND DISCUSSION
■
Glycal 4 (Scheme 1) was initially designed to be a donor, and
we speculated that it might show different reactivity in NIS-
To understand the reason for the preferred furanoside
formation in the NIS-mediated ring-closure step on alkene 6,
we hypothesized that the substituent attached to the double
bond played a crucial role in controlling the regioselectivity of
the ring closure. As illustrated in Scheme 3, the attack of the π-
Scheme 1. Initial Plan To Synthesize Kdo Glycal 4
Scheme 3. Possible Explanation for the C-Furanoside
Formation and a Proposed Strategy To Guide the Ring
Closure To Form C-Pyranosides
mediated glycosylation compared to 3, as the glycal 4 contains
two isopropylidene protecting groups, which are less electron-
withdrawing compared to acetate. Compound 4 could be
obtained from a base-catalyzed elimination of the iodide 5,
which in turn could be prepared from an NIS-mediated ring
closure of the alkene 6 (Scheme 2).24,25 The advantage of the
Scheme 2. NIS-Mediated Ring Closure of Alkene 626
electrons of the alkene on NIS can generate an iodonium which
can be considered as a hybrid of two carbocations A and B.
When the substituent R is an electron-withdrawing group such
as the carboxyl group found in compound 6, the carbocation B
should be less stable than A because in B the positive charge is
closer to the electron-deficient center; consequently, the attack
of OH-5 group on the more stable carbocation A should be
preferred. This led to the preferred formation of furanosides. If
our hypothesis holds true, we could substitute the R group with
another one that has the ability to stabilize the positive charge
developed at C-1this could force the attack of the OH-5 on
route is that the alkene 6 could be synthesized in large amount
from the commercially available D-mannose via the 2,3:5,6-di-
O-isopropylidene-D-mannofuranose 7 as an intermediate.
However, previous work from two other groups26 showed
that the NIS-mediated cyclization provided furanosides 8 as a
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C-1 during the ring-closure step to produce the desired
pyranosides. One such substituent is an aryl group because the
placement of such a group beside C-1 should make C-1 a
benzylic position, thus the positive charge developed at C-1
could be greatly stabilized by the aromatic ring.28 Previously,
thiophenyl group has been used to direct the NIS-mediated
cyclizations to pyranosides.29
(Figure 2), both compounds are C-pyranosides which had their
p-methoxyphenyl group projecting to the bottom face of the
In consideration of our ultimate goal which is to develop an
efficient synthesis for Kdo glycosides, this strategy could in fact
be advantageous because the aryl group could be considered as
a masked carboxyl group, which could be revealed after an
oxidation using strong oxidants such ruthenium(III) chlor-
ide30−33 or ozone.34 To test this idea, we designed the alkene
11 (Scheme 3), which had a p-methoxyphenyl group directly
attached to the double bond, as our novel synthetic target.
As shown in Scheme 4, starting from the known p-
methoxybenzyltriphenylphosphonium chloride (12),35 we
Scheme 4. Novel Strategy To Synthesize C-Aryl Pyranosides
and Form Glycal 17
Figure 2. Thermal ellipsoid plot (ORTEP) of compounds 14 and 15.
1
pyranose ring. H NMR experiment revealed that compound
14 had a small J1,2 coupling constant (1.6 Hz), while compound
15 had a larger J1,2 (11.2 Hz). A subsequent radical
deiodination on either compound resulted in the formation
of the same compound 16
We subsequently studied the base-catalyzed elimination of 2-
iodides 14 and 15. When 14 was subjected to a treatment with
1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), the glycal 17 was
obtained in high yield (84%) after 1 h at room temperature.
However, when compound 15 was treated with DBU under the
same conditions, no elimination product was formed, even after
we extended the reaction time or subjected the reaction at
elevated temperatures. Clearly, there are considerable differ-
ences in their reactivities when subjected to the base-catalyzed
elimination. In the case of 14, the 2-iodide is in an anti-
relationship with the proton on C-1; thus, the E2-elimination is
favored. However, for 15, its 2-iodide is in a syn-relationship
with the proton on C-1; thus, the E2-elimination is difficult to
proceed. After trying several other conditions, we finally found
that the 2-iodide of 15 could be eliminated under much more
forcing conditions using the stronger potassium tert-butoxide as
a base and in refluxing toluene; after 18 h, the same glycal 17
was obtained in 80% yield.
generated the intermediate ylide 13 by treating with n-
butyllithium at −40 °C, and after a condensation with the
hemiacetal 7, the alkene 11 was obtained in 85% yield (E/Z
1.9: 1). Small amounts of pure E- and Z-isomers were obtained
by chromatography on silica gel using 2% dichloromethane−
acetone as the eluent.
With the alkene 11 in hand, we investigated the NIS-
mediated ring closure reaction. Theoretically, we could obtain
eight cyclized products, four furanosides and four pyranosides.
However, the NIS-mediated cyclization afforded only two
compounds 14 and 15, which were isolated in 22% (less polar)
and 43% (more polar) yields (Scheme 4), respectively.
Fortunately, we were able to obtain crystal structures36 of
both cyclized products. As shown from the solved structures
With the glycal 17 in hand, we proceeded to investigate its
glycosylation properties with alcohols. As shown in Scheme 5,
we first reacted 17 with the methanol as a model reaction; it
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galacto-heptose; according to the molecular model, in the
skewed conformation as shown in Scheme 5, the H-2 and H-3
have a dihedral angle of ∼60° which corresponds to a small
coupling constant; the 2-iodo group in 18α must occupy a
pseudo equatorial position to generate with a D-glycero-D-talo-
heptose. As shown in Scheme 5, in the skewed conformation,
the dihedral angle of H-2 and H-3 in 18α is ∼0°, which
corresponds to a larger coupling constant.
Scheme 5. Synthesis of Methyl Kdo Glycosides from Glycal
(17)
The RhCl3−NaIO4-mediated oxidation proceeded smoothly,
as the starting material was consumed rapidly according to TLC
analysis. However, if no base was present in the reaction
mixture, we found that oxidation gave a complex mixture. This
could be due to the presence of formic acid which was formed
from the oxidation of the aromatic ring; the acid could
hydrolyze either the Kdo glycoside or the isopropylidene acetal
or both. If we added NaHCO3 into the reaction media, the
oxidation was found to be too sluggish. The optimal condition
was to perform the oxidation at pH 7 in a 0.5 N phosphate
buffer.
Thus, it appeared that the NIS-mediated glycosylations on
glycal 17 preferred β-anomeric selectivity, which is surprising,
as it is opposite to what was previously observed on using
glycals such as 3 as a donor. To test the general applicability of
our methodology, we reacted glycal 17 with a series of alcohols
(Table 1) under the activation with NIS; to simplify the
process, the crude 2-iodides were not separated but directly
subjected to a radical deiodination to obtain 2-deoxy glycosides
which were then purified. As can be seen from Table 1, the
glycal 17 is capable of glycosylating both primary and
secondary alcohols to afford β-glycosides in high yields and
with excellent anomeric selectivity. The glycosylations were
especially selective for sterically nonhindered primary alcohols
(items a−e), which provided the β-ketopyranosides in high
yields (77−93%) and excellent anomeric selectivity (β/α >
15:1). If the steric bulkiness of the alcohol increased, the
anomeric selectivity slightly decreased, but the high β-selectivity
was maintained (β/α > 8:1, items f−h) and the yields of the
glycosides were still high (78−91%). We have also carried out a
preliminary study on testing the glycosylation properties of 17
with a glycosyl acceptor 28 (entry i), which has a primary
hydroxyl group, and the result showed that the reaction
proceeded in an analogous fashion as other primary alcohols to
furnish the glycoside 29 in 76% yield (β/α 8:1).
The much improved reactivity of donor 17 compared to 3
could be explained by the presence of the 1-C-aryl group as
opposed to the deactivating carboxylic group, which removes
electron density from the double bond. However, such
difference does not explain the opposite anomeric selectivities
between the two donors. Fortunately, we succeeded to obtain a
single crystal of glycal 17.36 From the solved crystal structure
(Figure 3), we clearly observe that one of the methyl groups of
the endocyclic isopropylidene is very close to the top face of the
glycal double bond. The shortest distance between one of the
hydrogen atoms of the methyl to C-2 is 3.14 Å.
was found that under the activation with NIS, the glycal was
consumed within 10 min at −78 °C. This illustrates a
significant enhancement of reactivity compared to glycal 3.
According to the TLC analysis, a very major compound was
formed along with a minor one. The two isomers were isolated
in 87% (18β) and 4% (18α) yields, respectively.
To determine the anomeric configuration of formed
products, the major isomer was subjected to a radical
deiodination as before to afford the 2-deoxy glycoside
intermediate in 93% yield. Using the conventional RhCl3−
NaIO4 as a reagent,30 the major product was oxidized to the
corresponding Kdo glycoside in 71% yield. Compared with the
1H NMR data of known literature compounds,37 we concluded
that the obtained compound was the β-Kdo glycoside 20β
(Scheme 5). Thus, logically, compound 19β must be the
corresponding deiodinated precursor and the 2-iodo glycoside
18β must have the same anomeric configuration as 19β. In a
similar manner, we think that the deiodinated 19α must be the
precursor of the α-Kdo glycoside 20α, and the 2-iodo glycoside
18α should have the same anomeric configuration as 19α. To
assign the configurations of C-2 centers of both 18β and 18α,
we compared their 1H NMR spectra. The H-2’s of both
compounds were observed as a doublet; however, compound
Thus, we think that observed anomeric selectivity during
NIS-mediated glycosylation could be rationalized by the steric
shielding effect of this methyl group. As shown in Scheme 6,
the fusing of the endocyclic isopropylidene protecting group
forces the pyranose ring of 17 to adopt a skewed conformation;
this brings the shaded methyl group closer to the top region of
the double bond, which sterically shields the top face. Thus, the
nucleophilic attack on NIS prefers to take place from the
bottom face of the ring which results in the formation of an
18β had a much smaller coupling constant for H-2/H-3 (J2,3
=
2.6 Hz) compared to 18α (J2,3 = 9.1 Hz). Therefore, we think
that the 2-iodo group in 18β must occupy a pseudoaxial
position, as this would generate the corresponding D-glycero-D-
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Table 1. Probing the Glycosylation Properties of Glycal 17
Figure 3. Thermal ellipsoid plot (ORTEP) of glycal 17.
β-glycosides E, the pyranose ring should adopt similar skewed
conformation as 14, this would set the 2-iodide in pseudo trans-
diaxial position relative to the anomeric OR group; thus, it
appears that although our glycal 17 provides the unexpected β-
glycosides compared to glycal 3, the NIS-mediated glyco-
sylations still follow similar electronic regime.38 Therefore, we
think that it is reasonable to conclude that the origin of the high
β-anomeric selectivity for glycal 17 is governed by both steric
and stereoelectronic controls. Although the strong stabilization
effect of the aromatic ring could also favor the formation of a 2-
iodo benzylic carbocation intermediate, this does not appear to
be the main glycosylation pathway, as the alcohol could attack
the benzylic cation from either the top (β-face) or bottom (α-
face). The attack from the bottom face appears to be less
sterically hindered; this would lead to the formation of
significant amounts of α-glycosides, which we did not observe.
CONCLUSIONS
■
In conclusion, we have developed a novel glycal donor 17 that
contains a 1-C-aryl group. Compared to previously known
glycal donors, the new glycal 17 exhibits much enhanced
reactivity under NIS-mediated glycosylations to furnish β-
glycosides in high anomeric selectivity and good to excellent
yields. Using the methyl glycoside as an example, we have
shown that the aryl group can be oxidized to provide the
corresponding β-Kdo glycosides in high yields. We are
currently studying other activation conditions or exploring
the use of other protecting groups to promote the synthesis of
α-Kdo glycosides.
EXPERIMENTAL SECTION
■
General Methods. Optical rotations were determined in a 5 cm
cell at 25 2 °C. [α]25D values are given in units of 10−1 deg cm2 g−1.
Analytical TLC was performed on silica gel 60-F254 with detection by
quenching of fluorescence and/or by charring with 5% sulfuric acid in
water or with a ceric ammonium molybdate dip. All commercial
reagents were used as supplied unless otherwise stated. Column
chromatography was performed on silica gel 60. Organic solutions
from extractions were dried with anhydrous Na2SO4 prior to
concentration under vacuum at <45 °C (bath). NMR spectra were
recorded at 300 or 400 MHz (1H) or at 50, 75, or 100 MHz (13C).
The first-order proton chemical shifts δH and δC are reported in δ
(ppm) and referenced to either residual CHCl3 (δH 7.24, δC 77.0,
CDCl3), residual CD3COCD2H (δH 2.06, δC 29.92, CD3COCD3), or
a
Yields are combined including glycosylation and radical deiodination.
Ratios were determined using crude mixtures of 2-iodides by 1D H
b
1
NMR experiment.
intermediate cyclic iodonium (C) rather than the unfavorable
D; a subsequent attack by an alcohol from the top face at the
anomeric center produces the observed β-glycosides (E) as a
major product. In addition, when closely examining the crystal
structure of compound 14, we observed that in the skewed
conformation, the 2-iodide and anomeric β-hydrogen in fact
have a pseudo trans-diaxial relationship, we conjecture that for
residual CD2HOD (δH 3.30, δC 49.5, CD3OD). H and 13C NMR
1
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chromatography on silica gel using a mixture of EtOAc−hexane
(10:90) as eluent to give compound 8 as a 7:1 mixture (410 mg, 0.899
mmol, 59.4%): Rf 0.44 (EtOAc/hexane 20:80); for the major product,
1H NMR (400 MHz, CDCl3) δ 4.86 (dd, 1H, J = 3.4, 6.0 Hz, H-4),
Scheme 6. (a) Proposed Mechanism for the NIS-Mediated
Addition of Glycal 17; (b) Molecular Model of β-Glycoside
E To Illustrate the Pseudo-Trans-Diaxial Relationship
between 2-Iodide and O1
4.74 (dd, 1H, J = 3.6, 6.0 Hz, H-5), 4.38 (d, 1H, J = 10.5 Hz, H-2),
4.34 (ddd, 1H, J = 4.4, 6.1, 7.8 Hz, H-7), 4.27−4.18 (m, 2H, OCH2),
4.07 (dd, 1H, J = 3.5, 10.5 Hz, H-3), 4.03 (dd, 1H, J = 6.1, 8.8 Hz, H-
8b), 3.99 (dd, 1H, J = 4.4, 8.8 Hz, H-8a), 3.59 (dd, 1H, J = 3.6, 7.8 Hz,
H-6), 1.49 (s, 3H, C(CH3)2), 1.41 (s, 3H, C(CH3)2), 1.36 (s, 6H, 2 ×
C(CH3)2), 1.28 (t, 3H, J = 7.2 Hz, OCH2CH3); 13C NMR (100 MHz,
CDCl3) δ 169.8 (CO), 112.8 (C(CH3)2), 109.3 (C(CH3)2), 82.9 (C-
6), 82.7 (C-3), 81.0 (C-4), 80.3 (C-5), 72.9 (C-7), 66.8 (C-8), 61.9
(OCH2), 26.9 (C(CH3)2), 25.8 (C(CH3)2), 25.3 (C(CH3)2), 24.6
(C(CH3)2), 14.8 (C-2), 13.8 (OCH2CH3).
Ethyl 3,6-Anhydro-2-deoxy-4,5:7,8-di-O-isopropylidene-D-
manno-octanoate (9). A solution of the above mixture of 8
(200.0 mg, 0.438 mmol), n-Bu3SnH (153.1 mg, 0.526 mmol), and a
catalytic amount AIBN in toluene (4.0 mL) was heated to reflux. After
3 h, the mixture was diluted with CH2Cl2, washed with 1% aqueous
solution of NH3·H2O, dried with anhydrous Na2SO4, and concen-
trated under reduced pressure. The crude mixture was purified by
column chromatography on silica gel using a mixture of EtOAc−
hexane (15:85) as eluent to provide compound 927 as a pure
compound (120.1 mg, 0.363 mmol, 83.0%): Rf 0.33 (EtOAc/hexane
80:20); 1H NMR (400 MHz, CDCl3) δ 4.79−4.73 (m, 2H, H-4 + H-
5), 4.38 (ddd, 1H, J = 4.8, 6.1, 7.7 Hz, H-7), 4.20−4.12 (m, 2H,
OCHaHbCH3 + OCHaHbCH3) 4.08 (dd, 1H, J = 6.1, 8.6 Hz, H-8a),
4.03 (dd, 1H, J = 4.5, 8.6 Hz, H-8b), 3.94 (m, 1H, H-3), 3.51 (dd, 1H,
J = 3.1, 7.7 Hz, H-6), 2.79 (dd, 1H, J = 7.3, 16.8 Hz, H-2a), 2.71 (dd,
1H, J = 6.4, 16.8 Hz, H-2b), 1.47 (s, 3H, C(CH3)2), 1.44 (s, 3H,
C(CH3)2), 1.37 (s, 3H, C(CH3)2), 1.33 (s, 3H, C(CH3)2), 1.27 (t, 3H,
J = 7.1 Hz, OCHaHbCH3); 13C NMR (100 MHz, CDCl3) δ 171.0
(CO), 112.5 (C(CH3)2), 109.1 (C(CH3)2), 81.6 (C-6), 81.1 (C-5),
80.7 (C-4), 77.8 (C-3), 73.1 (C-7), 66.9 (C-8), 60.6 (OCH2CH3),
33.6 (C-2), 26.9 (C(CH3)2), 25.7 (C(CH3)2), 25.3 (C(CH3)2), 24.7
(C(CH3)2), 14.2 (OCH2CH3); HRMS (ESI) calcd m/z for C16H27O7
(M + H+) 331.17513, found 331.17538. Anal. Calcd for C16H26O7: C,
58.17; H, 7.93. Found: C, 58.30; H, 8.01.
(E)-1,2-Dideoxy-3,4:6,7-di-O-isopropylidene-1-C-(4-methox-
yphenyl)-D-manno-hept-1-enitol (11E) and (Z)-1,2-Dideoxy-
3,4:6,7-di-O-isopropylidene-1-C-(4-methoxyphenyl)-D-manno-
hept-1-enitol (11Z). A solution of p-methoxybenzyltriphenylphos-
phonium chloride35 (8.0 g, 19.1 mmol) in anhydrous THF (40 mL)
was cooled to −40 °C under Ar, and a solution of n-BuLi in hexane
(1.6 M, 12.0 mL, 19.2 mmol) was added dropwise. The mixture turned
yellow, and the stirring was continued at −40 °C for 1 h to generate
the ylide solution. In another flask, the hemiacetal 7 (4.14 g, 15.9
mmol) was dissolved in anhydrous THF (10 mL) under Ar, and a
solution of n-BuLi in hexane (1.6 M, 10.0 mL, 16.0 mmol) was added
dropwise. After being stirred for 10 min, the solution was transferred
to the above prepared ylide solution, and the combined mixture was
stirred at −40 °C for 1 h, warmed to room temperature within 1 h, and
subsequently heated to reflux for 20 h. The reaction mixture was
poured into cold water (80 mL) and the mixture was extracted with
CH2Cl2 (3 × 120 mL); the combined organic solution was washed
with saturated brine, dried with anhydrous Na2SO4, and concentrated.
The residue was purified by column chromatography on silica gel
using a mixture of EtOAc−hexane (10: 90) as eluent to give
compound 11 (4.93 g, 13.5 mmol, yield 85%) as a mixture of isomers
(E/Z 1.9: 1 according to NMR): Rf 0.17 (CH2Cl2/acetone 95:5). Pure
11Z and 11E could be obtained in small amounts by column
spectra were assigned with the assistance of GCOSY, GHSQC spectra.
Mass spectra were obtained by standard EI, CI, or ESI techniques as
indicated.
chromatography on silica gel using a mixture of CH2Cl2/acetone
Ethyl 3,6-Anhydro-2-deoxy-2-iodo-4,5:7,8-di-O-isopropyli-
dene-D-glycero-D-talo/galacto-octanoate (8). To a solution of
(E)-ethyl 2,3-dideoxy-4,5:7,8-di-O-isopropylidene-D-manno-2-octe-
noate (7,24 500.0 mg, 1.51 mmol) in anhydrous MeCN (3.0 mL)
was added NIS (510.8 mg, 2.270 mmol), and the mixture was stirred
for 3 h at room temperature. The mixture was diluted with EtOAc,
washed with a 10% aqueous solution of Na2S2O3, and the organic layer
was separated, dried with anhydrous Na2SO4, and concentrated under
reduced pressure. The crude mixture was purified by column
1
(98:2) as eluent. Data for 11Z: [α]25 −168.2 (c 0.5, CH2Cl2); H
D
NMR (400 MHz, CDCl3) δ 7.22−7.12 (m, 2H, H-2_MBn + H-
6_MBn), 6.94−6.86 (m, 2H, H-3_MBn + H-5_MBn), 6.75 (d, 1H, J
= 11.6 Hz, H-1), 5.97 (dd, 1H, J = 8.8, 11.6 Hz, H-2), 5.20 (ddd, 1H, J
= 1.0, 7.7, 8.8 Hz, H-3), 4.55 (dd, 1H, J = 1.0, 8.3 Hz, H-4), 4.15−4.00
(m, 3H, H-7b + H-7a + H-6), 3.78 (s, 3H, OCH3), 3.59 (ddd, 1H, J =
1.0, 8.3, 9.1 Hz, H-5), 2.35 (d, 1H, J = 9.1 Hz, OH_C-5), 1.56 (s, 3H,
C(CH3)2), 1.40 (s, 3H, C(CH3)2), 1.36 (s, 6H, 2 × C(CH3)2); 13C
101
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Article
NMR (100 MHz, CDCl3) δ 159.1 (C-4_MBn), 133.5 (C-1), 129.7
(2C, C-2 + C-6_ MBn), 128.6 (C-1_MBn), 126.0 (C-2), 113.8 (2C,
C-3 + C-5_ MBn), 109.4 (C(CH3)2), 108.6 (C(CH3)2), 76.9 (C-4),
76.1 (C-6), 74.0 (C-3), 70.8 (C-5), 67.1 (C-7), 55.3 (OCH3), 26.9
(C(CH3)2), 26.6 (C(CH3)2), 25.3 (C(CH3)2), 24.2 (C(CH3)2);
HRMS (FAB) calcd m/z for C20H28O6 Na (M + Na+) 387.1778,
amount of AIBN were added, and the solution was heated to reflux.
After 5 h, the mixture was diluted with CH2Cl2 and washed with 1%
aqueous solution of ammonium hydroxide. The organic layer was
separated, dried over anhydrous Na2SO4, and concentrated. The
residue was purified by column chromatography on silica gel using a
mixture of EtOAc/hexane (20:80) as eluent to provide pure
found 387.1778. Anal. Calcd for C20H28O6: C, 65.91; H, 7.74. Found:
compound 16 (102 mg, 0.280 mmol, 98.0%): Rf 0.24 (EtOAc/hexane
1
1
C, 65.56; H, 7.61. Data for 11E: [α25 +25.1 (c 0.6, CH2Cl2); H
2:8); [α]25 +16.8 (c 0.5, CHCl3); H NMR (400 MHz, CDCl3) δ
D
D
NMR (400 MHz, CDCl3) δ 7.41−7.34 (m, 2H, H-2_MBn + H-
6_MBn), 6.91−6.84 (m, 2H, H-3_MBn + H-5_MBn), 6.70 (d, 1H, J
= 16.0 Hz, H-1), 6.37 (dd, 1H, J = 8.4, 16.0 Hz, H-2), 4.83 (ddd, 1H, J
= ∼1, 7.5, 8.3 Hz, H-3), 4.39 (dd, 1H, J = 1.1, 7.3 Hz, H-4), 4.14−3.96
(m, 3H, H-7b + H-6 + H-7a), 3.82 (s, 3H, OCH3), 3.51 (ddd, 1H, J =
1.1, 8.1, 8.1 Hz, H-5), 2.28 (d, J = 8.4 Hz, 1H, OH_C-5), 1.57 (s, 3H,
C(CH3)2), 1.47 (s, 3H, C(CH3)2), 1.40 (s, 3H, C(CH3)2), 1.35 (s,
3H, C(CH3)2); 13C NMR (100 MHz, CDCl3) δ 159.6 (C-4_MBn),
134.9 (C-1), 128.9 (C-1_MBn), 128.1 (2C, C-2_MBn + C-6_ MBn),
122.5 (C-2), 114.0 (2C, C-3 + C-5_ MBn), 109.3 (C(CH3)2), 108.5
(C(CH3)2), 79.3 (C-3), 76.9 (C-4), 76.2 (C-6), 70.8 (C-5), 67.1 (C-
7), 55.3 (OCH3), 26.8 (C(CH3)2), 26.7 (C(CH3)2), 25.3 (C(CH3)2),
24.5 (C(CH3)2); HRMS (FAB) calcd m/z for C20H28O6 Na (M +
Na+) 387.1778, found 387.1778. Anal. Calcd for C20H28O6: C, 65.91;
H, 7.74. Found: C, 65.66; H, 7.91.
7.27−7.22 (m, 2H, H-2_MBn + H-6_MBn), 6.91−6.86 (m, 2H, H-
3_MBn + H-5_MBn), 5.04 (dd, 1H, J = 3.9, 11.8 Hz, H-1), 4.61 (ddd,
1H, J = 2.7, 2.8, 8.2 Hz, H-3), 4.45 (dd, 1H, J = 1.6, 8.1 Hz, H-4), 4.29
(ddd, 1H, J = 5.3, 5.3, 8.2 Hz, H-6), 4.19−4.07 (m, 2H, H-7a + H-7b),
3.81 (s, 3H, OCH3), 3.69 (dd, 1H, J = 1.6, 8.1 Hz, H-5), 2.11 (ddd,
1H, J = 2.8, 4.0, 15.2 Hz, H-2eq), 1.92 (ddd, 1H, J = 2.8, 11.9, 15.0 Hz,
H-2ax), 1.59 (s, 3H, C(CH3)2), 1.45 (s, 3H, C(CH3)2) 1.43 (s, 3H,
C(CH3)2), 1.40 (s, 3H, C(CH3)2); 13C NMR (100 MHz, CDCl3) δ
158.9 (C-4_MBn), 135.8 (C-1_MBn), 126.7 (C-2_MBn + C-
6_MBn), 113.8 (C-3_MBn + C-5_MBn), 109.2 (C(CH3)2), 108.8
(C(CH3)2), 74.6 (C-6), 72.2 (C-4), 72.1 (C-5), 70.4 (C-3), 69.8 (C-
1), 67.2 (C-7), 55.3 (OCH3), 33.7 (C-2), 27.0 (C(CH3)2), 26.3
(C(CH3)2), 25.3 (C(CH3)2), 24.5 (C(CH3)2); HRMS (FAB) calcd m/
z for C20H28O6Na (M + Na+) 387.1778, found 387.1780. Anal. Calcd
for C20H28O6: C, 65.91; H, 7.74. Found: C, 65.52; H, 7.75.
1-(2-Deoxy-2-iodo-3,4:6,7-di-O-isopropylidene-D-glycero-α-
D-galacto-heptopyranosyl)-4-methoxybenzene (14) and 1-(2-
Deoxy-2-iodo-3,4:6,7-di-O-isopropylidene-D-glycero-α-D-talo-
heptopyranosyl)-4-methoxybenzene (15). Compound 11 (E/Z
1.9: 1, 500.0 mg, 1.37 mmol) was treated with NIS (370.0 mg, 1.64
mmol) in MeCN (10.0 mL) for 1 h at room temperature. The mixture
was diluted with EtOAc and washed with 10% aqueous solution of
Na2S2O3. The organic layer was dried over anhydrous Na2SO4 and
concentrated. The residue was purified by column chromatography on
silica gel using a mixture of EtOAc−hexane (10: 90) as eluent to yield
compounds 14 (150.2 mg, 22.3% yield) and 15 (286.4 mg, 43.2%
yield). Data for 14: Rf 0.44 (EtOAc/hexane 2:8); [α]25D +51.5 (c 0.6,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.26−7.19 (m, 2H, H-
2_MBn + H-6_MBn), 6.93−6.84 (m, 2H, H-3_MBn + H-5_MBn),
5.00 (dd, 1H, J = 1.5, 7.7 Hz, H-3), 4.83 (d, 1H, J = 1.6 Hz, H-1), 4.65
(dd, 1H, J = 1.7, 7.5 Hz, H-4), 4.45 (dd, 1H, J = 1.4, 8.4 Hz, H-5), 4.39
(ddd, 1H, J = 4.3, 6.0, 8.4 Hz, H-6), 4.21 (dd, 1H, J = 4.3, 8.7 Hz, H-
7b), 4.18 (dd, 1H, J = 1.6, 1.6 Hz, H-2), 4.17 (dd, 1H, J = 6.0, 8.8 Hz,
H-7a), 3.81 (s, 3H, OCH3), 1.59 (s, 3H, C(CH3)2), 1.49 (s, 3H,
C(CH3)2), 1.43 (s, 3H, C(CH3)2), 1.41 (s, 3H, C(CH3)2); 13C NMR
(100 MHz, CDCl3) δ 159.0 (C-4_MBn), 133.5 (C-1_MBn), 126.8
(C-2_MBn + C-6_MBn), 113.3 (C-3_MBn + C-5_MBn), 109.2 (2C,
2 × C(CH3)2), 77.1 (C-3), 74.6 (C-6), 71.5 (C-4), 70.4 (C-5), 70.0
(C-1), 67.0 (C-7), 55.1 (OCH3), 36.7 (C-2), 26.9 (C(CH3)2), 26.6
(C(CH3)2), 25.4 (C(CH3)2), 24.0 (C(CH3)2); HRMS (FAB) calcd m/
z for C20H27IO6Na (M + Na+) 513.0745, found 513.0740. Anal. Calcd
1,5-Anhydro-2-deoxy-3,4:6,7-di-O-isopropylidene-1-C-(4-
methoxyphenyl)-D-manno-hept-1-enitol (17). Method 1: Com-
pound 14 (450 mg, 0.918 mmol) was treated with DBU (168 mg,
1.101 mmol) in MeCN (5.0 mL) for 1 h. The pale-pink solution was
concentrated under vacuum. The resulted oil was purified by column
chromatography on silica gel using a mixture of EtOAc−hexane
(85:15) as eluent to provide the desired glycal 17 (280 mg, 0.28 mmol,
84.0%). Method 2: To a solution of compound 15 (1.83 g, 3.73
mmol) in toluene (15.0 mL), was added t-BuOK (2.09 g, 18.64
mmol), and the mixture was refluxed for 15 h. The dark-red solution
was concentrated under the vacuum. The oily residue was purified by
column chromatography on silica gel using a mixture of EtOAc−
hexane (90:10) as eluent to afford glycal 17 (1.08 g, 2.98 mmol, 80.0%
yield): Rf 0.44 (EtOAc/hexane 2:8); [α]25D +163.9 (c 0.9, CHCl3); 1H
NMR (400 MHz, CDCl3) δ 7.53−7.45 (m, 2H, H-2_MBn + H-
6_MBn), 6.91−6.83 (m, 2H, H-3_MBn + H-5_MBn), 5.29 (dd, 1H, J
= 1.1, 3.5 Hz, H-2), 4.88 (dd, 1H, J = 3.5, 6.4 Hz, H-3), 4.56−4.48 (m,
2H, H-4 + H-6), 4.28−4.22 (m, 2H, H-7a + H-7b), 3.92 (dd, 1H, J =
1.1, 8.1 Hz, H-5), 3.81 (s, 3H, OCH3), 1.48 (s, 3H, C(CH3)2), 1.45−
1.38 (m, 9H, C(CH3)2); 13C NMR (100 MHz, CDCl3) δ 160.2 (C-
4_MBn), 152.6 (C-1), 127.0 (C-1_MBn), 126.4 (2C, C-2_MBn + C-
6_MBn), 113.6 (2C, C-3_MBn + C-5_MBn), 110.4 (C(CH3)2),
109.4 (C(CH3)2), 96.9 (C-2), 76.2 (C-5), 74.2 (C-6), 71.9 (C-4), 69.8
(C-3), 66.8 (C-7), 55.2 (OCH3), 28.1 (C(CH3)2), 27.0 (C(CH3)2),
26.9 (C(CH3)2), 25.3 (C(CH3)2); HRMS (ESI) calcd m/z for
C20H27O6 (M + H+) 363.1808, found 363.1813. Anal. Calcd for
C20H26O6: C, 66.28; H, 7.23. Found: C 65.98; H, 7.35.
1-(Methyl 2-deoxy-2-iodo-3,4:6,7-di-O-isopropylidene-D-
talo-α-D-galacto-heptopyranoside)-4-methoxybenzene (18α)
and 1-(Methyl 2-deoxy-2-iodo-3,4:6,7-di-O-isopropylidene-D-
glycero-β-D-galacto-heptopyranoside)-4-methoxybenzene
(18β). To a solution of glycal 17 (100 mg, 0.28 mmol) and anhydrous
methanol (60 μL, 1.46 mmol) in anhydrous CH2Cl2 (1.5 mL) was
added molecular sieves 3 Å (200 mg) under argon. The mixture was
stirred at −78 °C for 30 min, and NIS (93.2 mg, 0.414 mmol) was
added. After the mixture was stirred for 10 min, the insoluble material
was filtered off, and the filtrate was concentrated under reduced
pressure. The 1H NMR of the crude mixture showed the β-isomer was
predominantly formed (18β/18α > 20:1). The residue was purified by
column chromatography on silica gel using a mixture of hexane−
EtOAc (90:10) as eluent to afford the glycoside 18β (124.5 mg, 86.7%
for C20H27IO6: C, 48.99; H, 5.55. Found: C,49.27; H, 5.51. Data for
1
15: Rf 0.27 (EtOAc/hexane 2:8); [α]25 +58.3 (c 0.6, CHCl3); H
D
NMR (400 MHz, CDCl3) δ 7.31−7.24 (m, 2H, H-2_MBn + H-
6_MBn), 6.92−6.85 (m, 2H, H-3_MBn + H-5_MBn), 5.06 (d, 1H, J
= 11.2 Hz, H-1), 4.84 (dd, 1H, J = 2.5, 8.1 Hz, H-3), 4.53 (dd, 1H, J =
1.6, 8.1 Hz, H-4), 4.46 (dd, 1H, J = 2.5, 11.3 Hz, H-2), 4.25 (ddd, 1H,
J = 3.9, 6.2, 8.4 Hz, H-6), 4.03 (dd, 1H, J = 6.1, 8.9 Hz, H-7b), 3.92
(dd, 1H, J = 3.9, 8.9 Hz, H-7a), 3.83 (s, 3H, OCH3), 3.80 (dd, 1H, J =
1.5, 8.4 Hz, H-5), 1.63 (s, 3H, C(CH3)2), 1.49 (s, 3H, C(CH3)2), 1.44
(s, 3H, C(CH3)2), 1.37 (s, 3H, C(CH3)2); 13C NMR (100 MHz,
CDCl3) δ 159.6 (C-4_MBn), 133.2 (C-1_MBn), 128.4 (C-2_MBn +
C-6_MBn), 113.7 (C-3_MBn + C-5_MBn), 109.4 (C(CH3)2), 109.3
(C(CH3)2), 76.3 (C-1), 75.7 (C-3), 73.8 (C-6), 73.6 (C-4), 71.7 (C-
5), 67.0 (C-7), 55.2 (OCH3), 28.8 (C-2), 27.0 (C(CH3)2), 26.1
(C(CH3)2), 25.0 (C(CH3)2), 24.6 (C(CH3)2); HRMS (FAB) calcd m/
z for C20H27IO6 Na (M + Na+) 513.0745, found 513.0748. Anal. Calcd
for C20H27IO6: C, 48.99; H, 5.55. Found: C, 49.25; H, 5.42.
yield) and glycoside 18α (6.0 mg, 4.2% yield). Data for 18β isomer:
1
Rf 0.14 (EtOAc/hexane 1:9); [α]25 +40.3 (c 1.0, CHCl3); H NMR
D
(400 MHz, CDCl3) δ 7.48−7.34 (m, 2H, H-2_MBn + H-6_MBn),
6.93−6.81 (m, 2H, H-3_MBn + H-5_MBn), 5.12 (dd, 1H, J = 2.5, 7.8
Hz, H-3), 4.55 (d, 1H, J = 2.6 Hz, H-2), 4.53 (dd, 1H, J = 2.6, 7.9 Hz,
H-4), 4.44 (ddd, 1H, J = 5.1, 6.3, 7.4 Hz, H-6), 4.34 (m, 1H, H-5),
2-Deoxy-3,4:6,7-di-O-isopropylidene-α,β-D-manno-hepto-
pyranoside-4-methoxybenzene (16). A mixture of compounds
14/15 (140.0 mg, 0.286 mmol), obtained as above, was dissolved in
toluene (4.0 mL), n-Bu3SnH (124.7 mg, 0.428 mmol) and a catalytic
102
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Article
4.28 (dd, 1H, J = 5.0, 8.6 Hz, H-7b), 4.20 (dd, 1H, J = 6.2, 8.8 Hz, H-
7a), 3.82 (s, 3H, OCH3_MBn), 3.06 (s, 3H, OCH3), 1.57 (s, 3H,
C(CH3)2), 1.47 (s, 3H, C(CH3)2), 1.42 (s, 3H, C(CH3)2), 1.38 (s,
3H, C(CH3)2); 13C NMR (100 MHz, CDCl3) δ 159.7 (C-4_MBn),
134.5 (C-1_MBn), 128.3 (C-2_MBn + C-6_MBn), 113.2 (C-3_MBn
+ C-5_MBn), 109.8 (C(CH3)2), 109.3 (C(CH3)2), 100.7 (C-1), 77.8
(C-4),75.0 (C-6), 71.6 (C-5), 71.0 (C-3), 66.8 (C-7), 55.2
(OCH3_MBn), 50.5 (OCH3), 33.0 (C(CH3)2), 26.9 (C(CH3)2),
25.6 (C(CH3)2), 25.5 (C(CH3)2), 24.7 (C(CH3)2). Data for the 18α
isomer: Rf 0.17 (EtOAc/hexane 1: 9); 1H NMR (400 MHz, CDCl3) δ
7.52−7.45 (m, 2H, H-3_MBn + H-5_MBn), 6.93−6.86 (m, 2H, H-
2_MBn + H-6_MBn), 4.74 (dd, 1H, J = 5.0, 9.2 Hz, H-3), 4.50 (ddd,
1H, J = 5.6, 5.6, 6.8 Hz, H-6), 4.22 (dd, 1H, J = 2.4, 5.0 Hz, H-4),
4.17−4.12 (m, 2H, H-7b + H-7a), 4.07 (dd, 1H, J = 2.5, 6.9 Hz, H-5),
3.83 (s, 3H, OCH3_MBn), 3.82 (d, 1H, J = 9.1 Hz, H-2), 3.21 (s, 3H,
OCH3), 1.52 (s, 3H, C(CH3)2), 1.43 (s, 6H, 2 × C(CH3)2), 1.41 (s,
3H, C(CH3)2); 13C NMR (100 MHz, CDCl3) δ 159.7 (C-1_MBn),
130.0 (C-4_MBn), 129.4 (C-3_MBn + C-5_MBn), 112.9 (C-2_MBn
+ C-6_MBn), 109.3 (2C, 2 × C(CH3)2), 101.5 (C-1), 80.0 (C-3), 74.8
(C-6), 72.8 (C-4), 69.0 (C-5), 66.4 (C-7), 55.2 (OCH3_MBn), 50.4
(OCH3), 41.2 (C-2), 28.4 (C(CH3)2), 26.9 (C(CH3)2), 26.3
(C(CH3)2), 25.6 (C(CH3)2). Anal. Calcd for C21H29IO7: C, 48.47;
H, 5.62. Found: C 48.83; H, 5.83.
NIS (0.8 mmol) was added, and the reaction was continued for 15 min
at the same temperature. After filtration, the organic solution was
concentrated. The residue was dissolved in EtOAc (20 mL), and the
organic solution was washed with an aqueous solution of NaS2O3
1
(10%) and dried over anhydrous Na2SO4. The H NMR of the crude
mixture was recorded to determine anomeric ratios of formed
glycosides, and the mixture was purified by column chromatography
on silica gel using a mixture of hexane/EtOAc (90:10) as eluent to
afford the desired 2-iodoglycosides as an anomeric mixture. The
above-obtained 2-iodoglycoside (0.19 mmol) was deiodinated with n-
Bu3SnH (0.376 mmol) and a catalytic amount of AIBN in toluene (3.0
mL) as before. The desired 2-iodoglycoside was obtained by column
chromatography on silica gel using a mixture of hexane/triethylamine
(98: 2) as eluent.
1-(Ethyl 2-deoxy-3,4:6,7-di-O-isopropylidene-β-D-manno-
heptopyranoside)-4-methoxybenzene (21β) and 1-(Ethyl 2-
deoxy-3,4:6,7-di-O-isopropylidene-α-D-manno-heptopyrano-
side)-4-methoxybenzene (21α). Compound 17 (150 mg, 0.414
mmol), ethanol (200 μL, 3.43 mmol), and NIS (195 mg, 0.867 mmol)
were reacted in a manner similar to that used above. The 1H NMR of
the crude mixture was recorded to determine anomeric ratios of
formed glycosides, and the mixture was passed through a thin layer of
silica gel using hexane/EtOAc (90:10) as eluent to afford the desired
2-iodoglycosides as an anomeric mixture. Part of the 2-iodoglycosides
(0.19 mmol) was deiodinated with n-Bu3SnH (100 μL, 0.376 mmol)
and a catalytic amount of AIBN as before, and the desired 2-
deoxyglycosides 21β and 21α were obtained by column chromatog-
raphy on silica gel using a mixture of hexane/triethylamine (98: 2) as
eluent (142.3 mg, 21β/21α: > 20/1, yield 91%). A small amount of
pure 21β and 21α was obtained by repeated column chromatography.
1-(Methyl 2-deoxy-3,4:6,7-di-O-isopropylidene-α-D-manno-
heptopyranoside)-4-methoxybenzene (19α) and 1-(Methyl 2-
deoxy-3,4:6,7-di-O-isopropylidene-β-D-manno-heptopyrano-
side)-4-methoxybenzene (19β). Compound 18β (100.0 mg, 0.192
mmol) was deiodinated with n-Bu3SnH (78 μL, 0.288 mol) and a
catalytic amount of AIBN in toluene (2.0 mL) as before. Glycoside
19β (70.6 mg, 93.2% yield) was obtained as a colorless foam by
column chromatography on silica gel using a mixture of hexane/
EtOAc/TEA (95:5:2) as eluent. The corresponding 18α anomer could
be deiodinated in the same manner. Data for 19β isomer: Rf 0.31
(EtOAc/hexane 20:80); [α]25D +1.0 (c 4.46, CH2Cl2); 1H NMR (400
MHz, acetone-d6) δ 7.49−7.34 (m, 2H, H-2_MBn + H-6_MBn),
7.02−6.87 (m, 2H, H-3_MBn + H-5_MBn), 4.42 (ddd, 1H, J = 4.5,
4.5, 7.6 Hz, H-3), 4.38−4.29 (m, 2H, H-6 + H-4), 4.24 (dd, 1H, J =
6.2, 8.4 Hz, H-7b), 4.14 (dd, 1H, J = 6.4, 8.6 Hz, H-7a), 3.83−3.77 (m,
4H, OCH3_MBn + H-5), 2.99 (s, 3H, OCH3), 2.23 (dd, 1H, J = 4.1,
14.9 Hz, H-2b), 2.01 (dd, 1H, J = 4.8, 15.0 Hz, H-2a), 1.48 (s, 3H,
C(CH3)2), 1.40 (s, 3H, C(CH3)2), 1.35 (s, 3H, C(CH3)2), 1.29 (s,
3H, C(CH3)2); 13C NMR (100 MHz, acetone-d6) δ 160.5 (C-
4_MBn), 135.0 (C-1_MBn), 128.7 (C-2_MBn + C-6_MBn), 114.4
(C-3_MBn + C-5_MBn), 109.5 (C(CH3)2), 109.3 (C(CH3)2), 101.1
(C-1), 76.6 (C-6), 73.3 (C-5), 72.5 (C-4), 71.5 (C-3), 67.0 (C-7), 55.6
(OCH3_MBn), 49.2 (OCH3), 38.3 (C-2), 27.0 (C(CH3)2), 26.8
(C(CH3)2), 26.1 (C(CH3)2), 25.5 (C(CH3)2); HRMS (EI) calcd m/z
for C20H27O6 (M+ − OCH3) 363.1808, found 363.1800. Anal. Calcd
for C21H30O7: C, 63.94; H, 7.67. Found: C, 63.98; H, 7.78. Data for
Data for 21β: Rf 0.35 (EtOAc/hexane 20:80); [α]25 +3.6 (c 1.5,
D
1
CHCl3); H NMR (400 MHz, acetone-d6) δ 7.48−7.40 (m, 2H, H-
2_MBn + H-6_MBn), 6.98−6.90 (m, 2H, H-3_MBn + H-5_MBn),
4.41 (ddd, 1H, J = 4.5, 4.5, 7.4 Hz, H-3), 4.34 (ddd, 1H, J = 5.6, 6.4,
6.4 Hz, H-6), 4.27 (dd, 1H, J = 2.0, 7.5 Hz, H-4), 4.23 (dd, 1H, J = 6.4,
8.4 Hz, H-7b), 4.09 (dd, 1H, J = 6.4, 8.4 Hz, H-7a), 3.80 (s, 3H,
OCH3), 3.77 (dd, 1H, J = 1.9, 5.4 Hz, H-5), 3.54 (dq, 1H, J = 7.1, 9.5
Hz, OCHaHbCH3), 3.04 (dq, 1H, J = 7.1, 9.5 Hz, OCHaHbCH3), 2.27
(dd, 1H, J = 4.4, 15.0 Hz, H-2b), 2.03 (dd, 1H, J = 4.7, 14.8 Hz, H-2a),
1.47 (s, 3H, C(CH3)2), 1.37 (s, 3H, C(CH3)2), 1.34 (s, 3H,
C(CH3)2), 1.29 (s, 3H, C(CH3)2), 1.01 (t, 3H, J = 7.1 Hz,
OCH2CH3); 13C NMR (100 MHz, acetone-d6) δ 159.4 (C-
4_MBn), 134.6 (C-1_MBn), 127.5 (C-2_MBn + C-6_MBn), 113.4
(C-3_MBn + C-5_MBn), 108.4 (C(CH3)2), 108.2 (C(CH3)2), 100.2
(C-1), 75.7 (C-6), 72.2 (C-5), 71.6 (C-4), 70.7 (C-3), 65.8 (C-7), 56.9
(OCH2), 54.6 (OCH3), 37.2 (C-2), 26.0 (2C, C(CH3)2), 25.2
(C(CH3)2), 24.5 (C(CH3)2), 15.0 (OCH2CH3); HRMS (EI) calcd m/
+
z for C22H32O7 (M ) 408.2148, found 408.2140. Data for 21α: Rf
1
0.42 (EtOAc/hexane 20:80); [α]25 +68.1 (c 0.4, CHCl3); H NMR
D
19α isomer: Rf 0.39 for (EtOAc/hexane 20:80); [α]25 +89.8 (c 0.5,
(400 MHz, acetone-d6) δ 7.46−7.39 (m, 2H, H-2_MBn + H-6_MBn),
6.94−6.88 (m, 2H, H-3_MBn + H-5_MBn), 4.50 (ddd, 1H, J = 5.9,
5.9, 7.3 Hz, H-3), 4.44 (ddd, 1H, J = 6.1, 6.2, 6.2 Hz, H-6), 4.28 (dd,
1H, J = 2.4, 6.0 Hz, H-4), 4.15 (dd, 1H, J = 6.2, 12.1 Hz, H-7a), 4.13
(dd, 1H, J = 5.9, 12.0 Hz, H-7b), 4.13 (dd, 1H, J = 5.9, 8.6 Hz, H-7a),
3.94 (dd, 1H, J = 2.4, 6.4 Hz, H-5), 3.80 (s, 3H, OCH3), 3.29 (dq, 1H,
J = 7.1, 9.5 Hz, OCHaHbCH3), 3.02 (dq, 1H, J = 7.1, 9.7 Hz,
OCHaHbCH3), 2.26 (dd, 1H, J = 5.7, 14.1 Hz, H-2b), 1.89 (dd, 1H, J
= 7.5, 14.1 Hz, H-2a), 1.38 (s, 3H, C(CH3)2), 1.34 (s, 3H, C(CH3)2),
1.33 (s, 3H, C(CH3)2), 1.26 (s, 3H, C(CH3)2), 1.08 (t, 3H, J = 7.0 Hz,
CH3); 13C NMR (100 MHz, acetone-d6) δ 160.3 (C-4_MBn), 135.8
(C-1_MBn), 128.2 (C-2_MBn + C-6_MBn), 114.2 (C-3_MBn + C-
5_MBn), 109.4 (C(CH3)2), 109.2 (C(CH3)2), 101.1 (C-1), 76.1 (C-
6), 72.1 (C-4), 71.8 (C-3), 70.7 (C-5), 67.2 (C-7), 57.5 (OCH2), 55.6
(OCH3), 40.9 (C-2), 27.9 (C(CH3)2), 27.2 (C(CH3)2), 26.1
(C(CH3)2), 25.9 (C(CH3)2), 15.5 (OCH2CH3); HRMS (EI) calcd
m/z for C22H32O7 (M+) 408.2148, found 408.2144.
D
1
CH2Cl2); H NMR (400 MHz, acetone-d6) δ 7.45−7.37 (m, 2H, H-
2_MBn + H-6_MBn), 6.95−6.88 (m, 2H, H-3_MBn + H-5_MBn),
4.48 (ddd, 1H, J = 5.9, 5.9, 7.3 Hz, H-3), 4.44 (ddd, 1H, J = 6.1, 6.2,
6.2 Hz, H-6), 4.27 (dd, 1H, J = 2.3, 6.1 Hz, H-4), 4.19−4.11 (m, 2H,
H-7b + H-7a), 3.94 (dd, 1H, J = 2.3, 6.3 Hz, H-5), 3.81 (s, 3H,
OCH3), 2.25 (dd, 1H, J = 5.6, 14.2 Hz, H-2b), 1.86 (dd, 1H, J = 7.3,
14.1 Hz, H-2a), 1.40 (s, 3H, C(CH3)2), 1.35 (s, 3H, C(CH3)2), 1.34
(s, 3H, C(CH3)2), 1.27 (s, 3H, C(CH3)2); 13C NMR (100 MHz,
acetone-d6) δ 160.3 (C-4_MBn), 135.1 (C-1_MBn), 128.4 (C-
2_MBn + C-6_MBn), 114.2 (C-3_MBn + C-5_MBn), 109.4
(C(CH3)2), 109.2 (C(CH3)2), 101.3 (C-1), 76.0 (C-6), 72.1 (C-4),
71.8 (C-3), 70.7 (C-5), 67.3 (C-7), 55.6 (OCH3_MBn), 49.2
(OCH3), 40.7 (C-2), 27.9 (C(CH3)2), 27.2 (C(CH3)2), 26.1
(C(CH3)2), 25.9 (C(CH3)2); HRMS (EI) calcd m/z for C20H27O6
(M+ − OCH3) 363.1808, found 363.1808.
General Procedure for Sequential NIS-Mediated Glycosyla-
tion with Glycal 17 with Alcohols and Radical Deiodination. A
mixture containing compound 17 (0.40 mmol), alcohol (0.48−1.2
mmol), and molecular sieves 4 Å (200.0 mg) in anhydrous CH2Cl2
(2.0 mL) was stirred under argon for 30 min and cooled to −50 °C,
1-(Butyl 2-deoxy-3,4:6,7-di-O-isopropylidene-β-D-manno-
heptopyranoside)-4-methoxybenzene (22β) and 1-(Butyl 2-
deoxy-3,4:6,7-di-O-isopropylidene-α-D-manno-heptopyrano-
side)-4-methoxybenzene (22α). Compound 17 (150 mg, 0.414
103
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Article
1
mmol), n-butanol (200 μL, 2.19 mmol), and NIS (195 mg, 0.867
mmol) were reacted in a manner similar to that used above. The
obtained mixture was deiodinated with n-Bu3SnH (100 μL, 0.376
mmol) in a similar manner to afford a mixture of compounds 22β and
22α in 93% yield (22β/22α: > 20/1) using a mixture of hexane/
Data for 23α: [α]25 +19.4 (c 1.5, CH2Cl2); H NMR (400 MHz,
D
acetone-d6) δ 7.45−7.37 (m, 2H, H-2_MBn + H-6_MBn), 6.95−6.86
(m, 2H, H-3_MBn + H-5_MBn), 4.50 (ddd, 1H, J = 5.9, 5.8, 7.4 Hz,
H-3), 4.44 (ddd, 1H, J = 6.0, 6.0, 6.0 Hz, H-6), 4.28 (dd, 1H, J = 2.3,
6.0 Hz, H-4), 4.20−4.10 (m, 2H, H-7b + H-7a), 3.96 (dd, 1H, J = 2.3,
6.5 Hz, H-5), 3.79 (s, 3H, OCH3), 3.23 (dt, 1H, J = 6.6, 9.4 Hz,
OCHaHbCH2), 2.89 (dt, 1H, J = 6.5, 9.5 Hz, OCHaHbCH2), 2.22 (dd,
1H, J = 5.7, 14.0 Hz, H-2b), 1.84 (dd, 1H, J = 7.6, 14.1 Hz, H-2a),
1.52−1.20 (m, 32H, 20H_chain +4 × C(CH3)2), 0.88 (t, 3H, J = 7.0
Hz, CH3_Chain); 13C NMR (100 MHz, acetone-d6) δ 160.3 (C-
4_MBn), 135.7 (C-1_MBn), 128.2 (C-2_MBn + C-6_MBn), 114.2
(C-3_MBn + C-5_MBn), 109.4 (C(CH3)2), 109.2 (C(CH3)2), 100.9
(C-1), 76.1 (C-6), 72.1 (C-4), 71.8 (C-3), 70.7 (C-5), 67.2 (C-7), 61.9
(OCH2), 55.6 (OCH3), 40.9 (C-2), 32.7 (OCH2CH2CH2), 30.5
(OCH2CH2), 30.45−30.10 (6 × CH2_chain), 28.0 (C(CH3)2), 27.3
(C(CH3)2), 27.2 (CH2CH2CH3_chain), 26.1 (C(CH3)2), 25.9 (C-
(CH3)2), 23.4 (CH2CH3_chain), 14.4 (CH3_chain). Anal. Calcd for
C32H52O7: C, 70.04; H, 9.55. Found: C 69.68; H, 9.66.
triethylamine (98: 2) as eluent. Data for 22β: [α]25 +6.1 (c 0.5,
D
1
CHCl3); H NMR (400 MHz, acetone-d6) δ 7.49−7.42 (m, 2H, H-
2_MBn + H-6_MBn), 6.97−6.90 (m, 2H, H-3_MBn + H-5_MBn),
4.41 (ddd, 1H, J = 4.8, 4.8, 7.3 Hz, H-3), 4.35 (ddd, 1H, J = 5.2, 6.5,
6.5 Hz, H-6), 4.27−4.20 (m, 2H, H-4 + H-7b), 4.12 (dd, 1H, J = 6.4,
8.6 Hz, H-7a), 3.80 (s, 3H, OCH3), 3.76 (dd, 1H, J = 2.0, 5.1 Hz, H-
5), 3.51 (dt 1H, J = 6.3, 9.2 Hz, OCHaHbCH2), 3.00 (dt, 1H, J = 6.6,
9.2 Hz, OCHaHbCH2), 2.30 (dd, 1H, J = 4.9, 15.0 Hz, H-2b), 2.09
(dd, 1H, J = 4.7, 15.0 Hz, H-2a), 1.49 (s, 3H, C(CH3)2), 1.45−1.20
(m, 13H, OCHaHbCH2CH2CH3 + 3 × C(CH3)2), 0.80 (t, 3H, J = 7.3
Hz, CH3_butyl); 13C NMR (100 MHz, Acetone-d6) δ 159.4 (C-
4_MBn), 134.2 (C-1_MBn), 127.6 (C-2_MBn + C-6_MBn), 113.4
(C-3_MBn + C-5_MBn), 108.4 (C(CH3)2), 108.1 (C(CH3)2), 100.1
(C-1), 75.8 (C-6), 72.1 (C-5), 71.6 (C-4), 70.9 (C-3), 65.7 (C-7), 61.1
(OCH2), 54.6 (OCH3), 36.9 (C-2), 32.0 (OCH2CH2), 26.2
(C(CH3)2), 26.0 (C(CH3)2), 25.2 (C(CH3)2), 24.5 (C(CH3)2), 19.1
1-(Benzyl 2-deoxy-3,4:6,7-di-O-isopropylidene-β-D-manno-
heptopyranoside)-4-methoxybenzene (24β) and 1-(Benzyl 2-
deoxy-3,4:6,7-di-O-isopropylidene-α-D-manno-heptopyrano-
side)-4-methoxybenzene (24α). Compound 17 (80 mg, 0.22
mmol), benzyl alcohol (75 μL, 0.66 mmol), and NIS (99.6 mg, 0.44
mmol) were reacted in a manner similar to that used above. The
obtained mixture was deiodinated with n-Bu3SnH in a similar manner
to afford a mixture of compounds 24β and 24α in 82% yield (24β/
24α: 15/1) using a mixture of hexane/EtOAc/triethylamine (95: 5: 2)
as eluent. Data for 24β: Rf 0.38 (EtOAc/hexane 20:80); [α]25D +10.6
(c 1.1, CHCl3); 1H NMR (400 MHz, acetone-d6) δ 7.57−7.49 (m, 2H,
H-2_MBn + H-6_MBn), 7.32−7.15 (m, 5H, Ar−H_Bn), 6.98−6.91
(m, 2H, H-3_MBn + H-5_MBn), 4.59 (d, 1H, J = 11.9 Hz, CHb_Bn),
4.47 (ddd, 1H, J = 4.4, 4.4, 7.7 Hz, H-3), 4.37 (ddd, 1H, J = 5.4, 6.5,
6.5 Hz, H-6), 4.30 (dd, 1H, J = 2.0, 7.5 Hz, H-4), 4.27 (dd, 1H, J = 6.5,
8.5 Hz, H-7b), 4.14 (dd, 1H, J = 6.5, 8.5 Hz, H-7a), 4.09 (d, 1H, J =
11.9 Hz, CHa_Bn), 3.84 (dd, 1H, J = 2.0, 5.3 Hz, H-5), 3.80 (s, 3H,
OCH3), 2.43 (dd, 1H, J = 4.2, 15.2 Hz, H-2b), 2.11 (dd, 1H, J = 4.6,
15.2 Hz, H-2a), 1.41 (s, 3H, C(CH3)2), 1.39 (s, 3H, C(CH3)2), 1.35
(s, 3H, C(CH3)2), 1.27 (s, 3H, C(CH3)2); 13C NMR (100 MHz,
acetone-d6) δ 160.6 (C-4_MBn), 140.3 (C-1_Bn), 135.3 (C-1_MBn),
128.9 (Ar−C_Bn), 128.6 (C-3_MBn + C-5_MBn), 128.4 (Ar−
C_Bn), 127.8 (Ar−C_Bn), 114.5 (C-2_MBn + C-6_MBn), 109.4
(C(CH3)2), 109.2 (C(CH3)2), 101.5 (C-1), 76.7 (C-6), 73.4 (C-5),
72.6 (C-4), 71.7 (C-3), 66.8 (C-7), 64.6 (CH2_Bn), 55.6 (OCH3),
38.0 (C-2), 27.0 (C(CH3)2), 27.0 (C(CH3)2), 26.1 (C(CH3)2), 25.3
(C(CH3)2); HRMS (FAB) calcd m/z for C27H34O7 Na (M + Na+)
493.2197, found 493.2189. Data for 24α: Rf 0.43 (EtOAc/hexane
20:80); [α]25D +50.4 (c 1.6, CHCl3); 1H NMR (400 MHz, acetone-d6)
δ 7.59−7.50 (m, 2H, H-2_MBn + H-6_MBn), 7.35−7.21 (m, 5H,
Ar−H_Bn), 6.99−6.90 (m, 2H, H-3_MBn + H-5_MBn), 4.59−4.51
(m, 1H, H-3), 4.48 (ddd, 1H, J = 6.1, 6.1, 6.1 Hz, H-6), 4.35 (d, 1H, J
= 11.5, Hz, CHb_Bn), 4.31 (dd, 1H, J = 2.4, 6.2 Hz, H-4), 4.24−4.14
(m, 2H, H-7b + H-7a), 4.08 (dd, 1H, J = 2.2, 6.0 Hz, H-5), 3.97 (d,
1H, J = 11.5 Hz, CHa_Bn), 3.81 (s, 3H, OCH3), 2.33 (dd, 1H, J = 5.5,
14.3 Hz, H-2b), 2.00 (dd, 1H, J = 7.1, 14.3 Hz, H-2a), 1.37 (s, 3H,
C(CH3)2), 1.36 (s, 3H, C(CH3)2), 1.34 (s, 3H, C(CH3)2), 1.27 (s,
3H, C(CH3)2); 13C NMR (100 MHz, acetone-d6) δ 160.4 (C-
4_MBn), 139.6 (C-1_Bn), 135.5 (C-1_MBn), 129.1 (Ar−C_Bn),
128.5 (Ar−C_Bn), 128.4 (C-2_MBn + C-6_MBn), 128.1 (Ar−
C_Bn), 114.3 (C-3_MBn + C-5_MBn), 109.4 (C(CH3)2), 109.2
(C(CH3)2), 101.4 (C-1), 76.1 (C-6), 72.2 (C-4), 71.8 (C-3), 70.9 (C-
5), 67.1 (C-7), 64.2 (CH2_Bn), 55.6 (OCH3), 40.6 (C-2), 27.8
(C(CH3)2), 27.2 (C(CH3)2), 26.0 (C(CH3)2), 25.9 (C(CH3)2);
HRMS (FAB) calcd m/z for C27H34O7 Na (M + Na+) 493.2197,
found 493.2194.
+
(CH2CH3), 13.3 (CH3); HRMS (EI) calcd m/z for C24H36O7 (M )
436.2461, found 436.2460. Anal. Calcd for C24H36O7: C, 66.03; H,
8.31. Found: C 65.68; H, 8.34. Data for 22α: Rf 0.42 (EtOAc/hexane
2:8); [α]25D +76.6 (c 1.4, CH2Cl2); 1H NMR (400 MHz, acetone-d6) δ
7.48−7.37 (m, 2H, H-2_MBn + H-6_MBn), 6.97−6.86 (m, 2H, H-
3_MBn + H-5_MBn), 4.50 (ddd, 1H, J = 5.9, 5.9, 7.5 Hz, H-3), 4.44
(ddd, 1H, J = 6.0, 6.0, 6.0 Hz, H-6), 4.28 (dd, 1H, J = 2.4, 6.0 Hz, H-
4), 4.17 (high order dd, 1H, J = 6.0, 14.8 Hz, H-7a), 4.17 (high order
dd, 1H, J = 6.0, 14.8 Hz, H-7b), 3.96 (dd, 1H, J = 2.4, 6.4 Hz, H-5),
3.79 (s, 3H, OCH3), 3.24 (dt, 1H, J = 6.5, 9.5 Hz, OCHaHbCH2), 2.85
(dt, 1H, J = 6.4, 9.5 Hz, OCHaHbCH2), 2.22 (dd, 1H, J = 5.7, 13.9 Hz,
H-2b), 1.84 (dd, 1H, J = 7.5, 14.1 Hz, H-2a), 1.51−1.23 (m, 16H,
OCHaHbCH2CH2CH3 + + 4 × C(CH3)2), 0.85 (t, 3H, J = 7.3 Hz,
CH3_butyl); 13C NMR (100 MHz, acetone-d6) δ 160.2 (C-4_MBn),
135.7 (C-1_MBn), 128.2 (C-3_MBn + C-5_MBn), 114.1 (C-2_MBn
+ C-6_MBn), 109.4 (C(CH3)2), 109.1 (C(CH3)2), 100.9 (C-1), 76.0
(C-6), 72.1 (C-4), 71.8 (C-3), 70.6 (C-5), 67.2 (C-7), 61.6 (OCH2),
55.6 (OCH3), 40.9 (C-2), 32.6 (OCH2CH2), 27.9 (C(CH3)2), 27.2
(C(CH3)2), 26.1 (C(CH3)2), 25.9 (C(CH3)2), 20.3 (CH2CH3), 14.3
(CH3); HRMS (EI) calcd m/z for C24H36O7 (M+) 436.2461, found
436.2446.
1-(Dodecyl 2-deoxy-3,4:6,7-di-O-isopropylidene-β-D-manno-
heptopyranoside)-4-methoxybenzene (23β) and 1-(Dodecyl 2-
deoxy-3,4:6,7-di-O-isopropylidene-α-D-manno-heptopyrano-
side)-4-methoxybenzene (23α). Compound 17 (150 mg, 0.414
mmol), n-dodecanol (115.7 mg, 0.621 mmol), and NIS (139.7 mg,
0.621 mmol) were reacted a manner similar to that used above. The
obtained mixture was deiodinated with n-Bu3SnH in a similar manner
to afford a mixture of compounds 23β and 23α in 77% yield (23β/
23α: > 20/1) using a mixture of hexane/triethylamine (98: 2) as
1
eluent. Data for 23β: [α]25 +16.3 (c 1.0, CHCl3); H NMR (400
D
MHz, acetone-d6) δ 7.49−7.42 (m, 2H, H-2_MBn + H-6_MBn),
6.98−6.90 (m, 2H, H-3_MBn + H-5_MBn), 4.38 (ddd, 1H, J = 4.8,
4.8, 7.4 Hz, H-3), 4.33 (ddd, 1H, J = 5.3, 6.5, 6.5 Hz, H-6), 4.26−4.20
(m, 2H, H-4 + H-7b), 4.11 (dd, 1H, J = 6.5, 8.5 Hz, H-7a), 3.80 (s,
3H, OCH3), 3.75 (dd, 1H, J = 2.0, 5.2 Hz, H-5), 3.49 (dt, 1H, J = 6.4,
9.2 Hz, OCHaHbCH2), 3.00 (dt, 1H, J = 6.7, 9.2 Hz, OCHaHbCH2),
2.29 (dd, 1H, J = 5.0, 14.9 Hz, H-2b), 2.06 (overlapped, 1H, H-2b),
1.54−1.08 (m, 32H, 20H_chain +4 × C(CH3)2), 0.86 (t, 3H, J = 6.9
Hz, CH3); 13C NMR (100 MHz, acetone-d6) δ 160.4 (C-4_MBn),
135.2 (C-1_MBn), 128.6 (C-2_MBn + C-6_MBn), 114.3 (C-3_MBn
+ C-5_MBn), 109.4 (C(CH3)2), 109.1 (C(CH3)2), 101.1 (C-1), 76.8
(C-6), 73.1(C-5), 72.6 (C-4), 71.8 (C-3), 66.7 (C-7), 62.4 (OCH2),
55.6 (OCH3), 37.9 (C-2), 32.7 (OCH2CH2CH2), 30.8 (OCH2CH2),
30.5, 30.43, 30.42, 30.40, 30.2 (6CH2_chain,), 27.2 (C(CH3)2), 27.0
(CH2CH2CH3_chain), 26.9 (C(CH3)2), 26.2 (C(CH3)2), 25.4 (C-
(CH3)2), 23.4 (CH2CH3_chain), 14.4 (CH3_chain); HRMS (FAB)
calcd m/z for C32H52O7 Na (M + Na+) 571.3605, found 571.3586.
Anal. Calcd for C32H52O7: C, 70.04; H, 9.55. Found: C 70.46; H, 9.80.
1-(Isopropyl 2-deoxy-3,4:6,7-di-O-isopropylidene-β-D-
manno-heptopyranoside)-4-methoxybenzene (25β) and 1-
(Isopropyl 2-deoxy-3,4:6,7-di-O-isopropylidene-α-D-manno-
heptopyranoside)-4-methoxybenzene (25α). Compound 17
(200 mg, 0.552 mmol), benzyl alcohol (99.5 mg, 1.66 mmol), and
NIS (186.2 mg, 0.828 mmol) were reacted in a manner similar to that
104
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Article
used above. The obtained mixture was deiodinated with n-Bu3SnH in a
similar manner to afford a mixture of compounds 25β and 25α in 91%
yield (25β/25α: 10/1) using a mixture of hexane/triethylamine (98:
1H, J = 5.2, 6.5, 6.5 Hz, H-3), 4.42 (ddd, 1H, J = 5.3, 6.1, 6.1 Hz, H-6),
4.28−4.20 (m, 2H, H-4 + H-7b), 4.17−4.10 (m, 2H, H-7a + H-5),
3.80 (s, 3H, OCH3), 3.40−3.32 (m, 1H, H-1_cyclohexane), 2.26 (dd,
1H, J = 5.0, 14.3 Hz, H-2b), 2.08 (dd, 1H, J = 6.5, 14.4 Hz, H-2a), 1.95
(m, 1H, 1H_cyclohexane), 1.71−1.44 (m, 2H, 2H_cyclohexane),
1.42−0.82 (m, 19H, 4 × C(CH3)2 + 7H_cyclohexane); 13C NMR
(100 MHz, acetone-d6) δ 160.1 (C-1_MBn), 136.9 (C-4_MBn), 128.7
(C-3_MBn + C-5_MBn), 113.7 (C-2_MBn + C-6_MBn), 109.0
(C(CH3)2), 109.0 (C(CH3)2), 100.9 (C-1), 76.6 (C-6), 72.6 (C-4),
71.7 (C-3), 70.9 (C-1_cyclohexane), 70.2 (C-5), 66.6 (C-7), 55.5
(OCH3), 40.3 (C-2), 35.0 (C-2 or C-6_cyclohexane), 34.3 (C-6 or C-
2_cyclohexane), 27.3 (C(CH3)2), 27.1 (C(CH3)2), 26.4 (C-4_cyclo-
hexane), 25.9 (C(CH3)2), 25.6 (C(CH3)2), 25.2 (C-3 or C-
5_cyclohexane), 25.0 (C-5 or C-3_cyclohexane); HRMS (EI) calcd
m/z for C20H26O6 (M+ − C6H12O) 362.1729, found 362.1729.
1-(Cyclopentyl 2-deoxy-3,4:6,7-di-O-isopropylidene-β-D-
manno-heptopyranoside)-4-methoxybenzene (27β) and 1-
(Cyclopentyl 2-deoxy-3,4:6,7-di-O-isopropylidene-α-D-manno-
heptopyranoside)-4-methoxybenzene (27α). Compound 17
(200 mg, 0.552 mmol), cyclopentanol (95.1 mg, 1.11 mmol), and
NIS (186.2 mg, 0.828 mmol) were reacted in a manner similar to that
used above. The obtained mixture was deiodinated with n-Bu3SnH in a
similar manner to afford a mixture of compounds 27β and 27α in 91%
yield (27β/27α: 10/1) using a mixture of hexane/triethylamine (98:2)
as eluent. Data for 27β: Rf 0.36 (EtOAc/hexane 20:80); [α]25D +22.4
2) as eluent. Data for 25β: Rf 0.36 (EtOAc/hexane 20:80); [α]25
D
1
+11.0 (c 1.7, CH2Cl2); H NMR (400 MHz, acetone-d6) δ 7.54−7.45
(m, 2H, H-2_MBn + H-6_MBn), 6.99−6.88 (m, 2H, H-3_MBn + H-
5_MBn), 4.38 (ddd, 1H, J = 5.1, 5.1, 7.1 Hz, H-3), 4.33 (ddd, 1H, J =
4.7, 6.6, 6.6 Hz, H-6), 4.24 (dd, 1H, J = 6.8, 8.4 Hz, H-7b), 4.16 (dd,
1H, J = 2.0, 7.1 Hz, H-4), 4.12 (dd, 1H, J = 6.4, 8.4 Hz, H-7a), 3.80 (s,
3H, OMe), 3.79 (septet, 1H, J = 6.2 Hz, OCH(CH3)2), 3.75 (dd, 1H, J
= 2.1, 4.7 Hz, H-5), 2.32 (dd, 1H, J = 5.4, 14.9 Hz, H-2b), 2.15 (dd,
1H, J = 4.8, 14.8 Hz, H-2a), 1.48 (s, 3H, C(CH3)2), 1.44 (s, 3H,
C(CH3)2), 1.38 (s, 3H, C(CH3)2), 1.31 (s, 3H, C(CH3)2), 1.20 (d,
3H, J = 6.2 Hz, OCH(CH3)2), 0.84 (d, 3H, J = 6.2 Hz, OCH(CH3)2);
13C NMR (100 MHz, acetone-d6) δ 160.4 (C-4_MBn), 138.3 (C-
1_MBn), 128.8 (C-3_MBn + C-5_MBn), 114.3 (C-2_MBn + C-
6_MBn), 109.3 (C(CH3)2), 109.0 (C(CH3)2), 101.9 (C-1), 76.8 (C-
6), 73.1 (C-5), 72.5 (C-4), 72.0 (C-3), 66.6 (C-7), 65.9 (OCH-
(CH3)2), 55.6 (OCH3), 37.9 (C-2), 27.2 (C(CH3)2), 26.9 (C(CH3)2),
26.1 (C(CH3)2), 25.4 (C(CH3)2), 25.3 (OCH(CH3)2), 24.3 (OCH-
(CH3)2); HRMS (EI) calcd m/z for C22H31O7 (M+ − CH3) 407.2070,
found 407.2077. Data for 25α: Rf 0.52 (EtOAc/hexane 20:80); [α]25
+69.4 (c 0.9, CH2Cl2); H NMR (400 MHz, acetone-d6) δ 7.57−7.45
D
1
(m, 2H, H-2_MBn + H-6_MBn), 6.96−6.87 (m, 2H, H-3_MBn + H-
5_MBn), 4.50 (ddd, 1H, J = 5.1, 6.5, 6.5 Hz, H-3), 4.44 (ddd, 1H, J =
5.5, 6.1, 6.1 Hz, H-6), 4.31−4.23 (m, 2H, H-4 + H-7b), 4.20−4.12 (m,
2H, H-5 + H-7a), 3.81 (s, 3H, OCH3), 3.79 (septet, 1H, J = 6.2 Hz,
OCH(CH3)2), 2.31 (dd, 1H, J = 5.0, 14.3 Hz, H-2b), 2.04 (dd, 1H, J =
6.7, 14.3 Hz, H-2a), 1.40 (s, 3H, C(CH3)2), 1.36 (s, 3H, C(CH3)2),
1.28 (s, 3H, C(CH3)2), 1.25 (s, 3H, C(CH3)2), 1.17 (d, 3H, J = 6.2
Hz, OCH(CH3)2), 0.75 (d, 3H, J = 6.2 Hz, OCH(CH3)2); 13C NMR
(100 MHz, acetone-d6) δ 160.2 (C-4_MBn), 136.5 (C-1_MBn), 128.7
(C-2_MBn + C-6_MBn), 113.8 (C-3_MBn + C-5_MBn), 109.1
(C(CH3)2), 109.0 (C(CH3)2), 100.9 (C-1), 76.6 (C-6), 72.5 (C-4),
71.6 (C-3), 70.2 (C-5), 66.7 (C-7), 65.2 (OCH(CH3)2), 55.5
(OCH3), 40.4 (C-2), 27.4 (C(CH3)2), 27.1 (C(CH3)2), 25.9
(C(CH3)2), 25.7 (C(CH3)2), 24.8 (OCH(CH3)2), 24.1 (OCH-
(CH3)2); HRMS (EI) calcd m/z for C20H27O6 (M+ − OC3H7)
363.1808, found 363.1790. Anal. Calcd for C23H34O7: C, 65.38; H,
8.11. Found: C 65.69; H, 8.13.
1
(c 0.6, CH2Cl2); H NMR (400 MHz, acetone-d6) δ 7.49−7.43 (m,
2H, H-2_MBn + H-6_MBn), 6.96−6.90 (m, 2H, H-3_MBn + H-
5_MBn), 4.40 (ddd, 1H, J = 4.8, 4.8, 7.3 Hz, H-3), 4.34 (ddd, 1H, J =
5.1, 6.5, 6.5 Hz, H-6), 4.24 (dd, 1H, J = 6.7, 8.4 Hz, H-7b), 4.20 (dd,
1H, J = 2.0, 7.3 Hz, H-4), 4.12 (dd, 1H, J = 6.4, 8.4 Hz, H-7a), 4.01−
3.94 (m, 1H, OCH_cyclopentyl), 3.80 (s, 3H, OCH3), 3.75 (dd, 1H, J
= 2.0, 5.0 Hz, H-5), 2.31 (dd, 1H, J = 4.9, 15.0 Hz, H-2b), 2.07 (dd,
1H, J = 4.7, 14.9 Hz, H-2a), 1.86−1.76 (m, 1H, 1H_cyclopentyl),
1.75−1.22 (m, 19H, 7H_cyclopentyl +4 × C(CH3)2); 13C NMR (100
MHz, Acetone-d6) δ 160.3 (C-4_MBn), 136.0 (C-1_MBn), 128.7 (C-
2_MBn + C-6_MBn), 114.4 (C-3_MBn + C-5_MBn), 109.2
(C(CH3)2), 109.1 (C(CH3)2), 101.8 (C-1), 76.7 (C-6), 75.6 (C-
1_cyclopentyl), 73.2 (C-5), 72.5 (C-4), 71.8 (C-3), 66.8 (C-7), 55.6
(OCH3), 38.1 (C-2), 35.0 (C-2 or C-5_cyclopentyl), 34.5 (C-5 or C-
2_cyclopentyl), 27.1 (C(CH3)2), 27.0 (C(CH3)2), 26.2 (C(CH3)2),
25.2 (C(CH3)2), 24.5 (C-3 or C-4_cyclopentyl), 24.1 (C-4 or C-
5_cyclopentyl); HRMS (FAB) calcd m/z for C20H27 O6 (M+ − C5H9
1-(Cyclohexyl 2-deoxy-3,4:6,7-di-O-isopropylidene-β-D-
manno-heptopyranoside)-4-methoxybenzene (26β) and 1-
(Cyclohexyl 2-deoxy-3,4:6,7-di-O-isopropylidene-α-D-manno-
heptopyranoside)-4-methoxybenzene (26α). Compound 17
(150 mg, 0.414 mmol), cyclohexanol (100 μL, 1.23 mmol), and NIS
(139.7 mg, 0.621 mmol) were reacted in a manner similar to that used
above. The obtained mixture was deiodinated with n-Bu3SnH in a
similar manner to afford a mixture of compounds 26β and 26α in 78%
yield (26β/26α: 8/1) using a mixture of hexane/triethylamine (98:2)
as eluent. Data for 26β: Rf 0.38 (EtOAc/hexane 20:80); [α]25D +12.4
O1) 363.1808, found 363.1800. Data for 27α: Rf 0.45 (EtOAc/hexane
1
20:80); [α]25 +84.2 (c 0.4, CH2Cl2); H NMR (400 MHz, acetone-
D
d6) δ 7.49−7.42 (m, 2H, H-2_MBn + H-6_MBn), 6.93−6.85 (m, 2H,
H-3_MBn + H-5_MBn), 4.50−4.41 (m, 2H, H-3 + H-6), 4.26 (dd,
1H, J = 2.4, 6.2 Hz, H-4), 4.20 (dd, 1H, J = 5.5, 8.6 Hz, H-7b), 4.18
(dd, 1H, J = 6.4, 8.6 Hz, H-7a), 4.08 (dd, 1H, J = 2.4, 6.2 Hz, H-5),
3.93−3.85 (m, 1H, OCH_cyclopentyl), 3.81 (s, 3H, OCH3), 2.30 (dd,
1H, J = 5.5, 14.1 Hz, H-2b), 1.93 (dd, 1H, J = 7.3, 14.1 Hz, H-2a),
1.85−1.76 (m, 1H, 1H_cyclopentyl), 1.64−1.03 (m, 19H, 7H_cyclo-
pentyl +4 × C(CH3)2); 13C NMR (100 MHz, acetone-d6) δ 160.2 (C-
4_MBn), 136.5 (C-1_MBn), 128.6 (C-3_MBn + C-5_MBn), 113.9
(C-2_MBn + C-6_MBn), 109.3 (C(CH3)2), 109.1 (C(CH3)2), 101.0
(C-1), 76.2 (C-6), 74.6 (C-1_cyclopentyl), 72.2 (C-4), 71.7 (C-3),
70.4 (C-5), 67.0 (C-7), 55.6 (OCH3), 40.4 (C-2), 34.5 (C-2 or C-
5_cyclopentyl), 34.1 (C-5 or C-2_cyclopentyl), 27.8 (C(CH3)2), 27.2
(C(CH3)2), 26.0 (C(CH3)2), 25.9 (C(CH3)2), 23.9 (C-3 or C-
4_cyclopentyl), 23.9 (C-4 or C-3_cyclopentyl); HRMS (FAB) calcd
m/z for C20H27 O6 (M+ − C5H9 O1) 363.1808, found 363.1809.
Methyl O-(2-Deoxy-3,4:6,7-di-O-isopropylidene-1-C-p-me-
thoxyphenyl-β-D-manno-heptopyranosyl)-(1→6)-2,3,4-tri-O-
benzyl-α-D-glucopyranoside (29β) and Methyl O-(2-Deoxy-
3,4:6,7-di-O-isopropylidene-1-C-p-methoxyphenyl-α-D-manno-
heptopyranosyl)-(1→6)-2,3,4-tri-O-benzyl-α-D-glucopyrano-
side (29α). A mixture containing compound 17 (30 mg, 0.083
mmol), methyl 2,3,4-tri-O-benzyl-α-D-glucopyranoside (46.2 mg,
0.099 mmol), and molecular sieves 4 Å (80.0 mg) in anhydrous
CH2Cl2 (0.8 mL) was purged with argon and stirred for 30 min. The
mixture was then cooled to −50 °C, and NIS (26.8 mg, 0.119 mmol)
was added. The reaction was stirred for another 20 min and slowly
1
(c 1.0, CH2Cl2); H NMR (400 MHz, acetone-d6) δ 7.55−7.47 (m,
2H, H-2_MBn + H-6_MBn), 6.98−6.87 (m, 2H, H-3_MBn + H-
5_MBn), 4.42 (ddd, 1H, J = 5.3, 5.3, 7.0 Hz, H-3), 4.32 (ddd, 1H, J =
4.3, 6.8, 6.8 Hz, H-6), 4.26 (dd, 1H, J = 7.0, 8.4 Hz, H-7b), 4.16−4.07
(m, 2H, H-4+ H-7a), 3.86 (s, 3H, OCH3), 3.77 (dd, 1H, J = 2.1, 4.3
Hz, H-5), 3.58−3.46 (m, 1H, H-1_cyclohexane), 2.29 (dd, 1H, J = 5.6,
14. Eight Hz, H-2b), 2.11 (dd, 1H, J = 4.8, 14.8 Hz, H-2a), 1.98−1.87
(m, 1H, 1H_cyclohexane), 1.76−0.92 (m, 21H, 9H_cyclohexane +4 ×
C(CH3)2); 13C NMR (100 MHz, acetone-d6) δ 160.4 (C-4_MBn),
135.2 (C-1_MBn), 128.9 (C-2_MBn + C-6_MBn), 114.3 (C-3_MBn
+ C-5_MBn), 109.3 (C(CH3)2), 108.9 (C(CH3)2), 101.8 (C-1), 77.0
(C-6), 73.0 (C-5), 72.6 (C-4), 72.2 (C-3), 71.7 (OCH), 66.5 (C-7),
55.6 (OCH3), 37.8 (C-2), 36.0 (C-2 or C-6_cyclohexane), 34.7 (C-6
or C-2_cyclohexane), 27.4 (C(CH3)2), 26.8 (C(CH3)2), 26.5 (C-
4_cyclohexane), 26.3 (C(CH3)2), 25.4 (C(CH3)2), 25.2 (C-3 or C-
5_cyclohexane), 25.1 (C-5 or C-3_cyclohexane); HRMS (EI) calcd
m/z for C20H27O6 (M+ − C6H11O) 363.1808, found 363.1820. Data
for 26α: Rf 0.47 (EtOAc/hexane 20:80); [α]25D +68.4 (c 0.7, CH2Cl2);
1H NMR (400 MHz, acetone-d6) δ 7.52−7.45 (m, 2H, H-2_MBn +
H-6_MBn), 6.92−6.84 (m, 2H, H-3_MBn + H-5_MBn), 4.49 (ddd,
105
dx.doi.org/10.1021/jo201531j | J. Org. Chem. 2012, 77, 96−107

The Journal of Organic Chemistry
Article
warmed to rt. The reacted was worked up as before, and the crude
mixture was passed through a thin layer of silica gel using hexane/
EtOAc (90: 10) as eluent to give the 2-iodoglycosides as an anomeric
mixture (65.5 mg). Part of the 2-iodides (30.0 mg, 0.032 mmol) was
deiodinated with n-Bu3SnH (6.0 μL, 0.022 mmol) in the presence of a
catalytic amount of AIBN in toluene (1.0 mL) to provide the desired
disaccharide 29β and 29α in 76% yield (29β/29α: 8/1) using a
mixture of hexane/EtOAc/triethylamine (85:15:5) as eluent. A small
amount of pure 29β and 29α was obtained in pure form by column
(OCH3), 33.6 (C-3), 25.9 (C(CH3)2), 25.7 (C(CH3)2), 24.2
(C(CH3)2), 24.2 (C(CH3)2); HRMS (FAB) calcd m/z for
C15H24O8Na (M + Na+) 355.1363, found 355.1365.
(Methyl 3-deoxy-4,5:7,8-di-O-isopropylidene-β-D-manno-2-
octulopyranosid)onic Acid (20β). Compound 19β isomer (57
mg, 0.15 mmol) was oxidized in a manner similar to that for 19α with
NaIO4 (619 mg, 2.89 mmol) and a catalytic amount of RuCl3·H2O.
The desired carboxylate was obtained by column chromatography on
silica gel using a mixture of CH2Cl2/MeOH/NH3·H2O (95:5:2) as
eluent to provide compound 20β (34 mg, 71% yield): Rf 0.30
(CH2Cl2/MeOH 8:2); 1H NMR (400 MHz, acetone-d6) δ 4.53 (ddd,
1H, J = 3.3, 3.8, 7.4 Hz, H-4), 4.37−4.29 (m, 2H, H-7 + H-5), 4.09
(dd, 1H, J = 6.2, 8.6 Hz, H-8b), 3.98 (dd, 1H, J = 5.5, 8.6 Hz, H-8a),
3.98 (dd, 1H, J = 5.5, 8.6 Hz, H-6), 3.27 (s, 3H, OCH3), 2.62 (dd, 1H,
J = 3.9, 15.4 Hz, H-3b), 1.94 (dd, 1H, J = 3.2, 15.4 Hz, H-3a), 1.39 (s,
3H, C(CH3)2), 1.38 (s, 3H, C(CH3)2), 1.32 (s, 3H, C(CH3)2), 1.29
(s, 3H, C(CH3)2); 13C NMR (100 MHz, acetone-d6) δ 169.8
(COOH), 109.6 (C(CH3)2), 109.5 (C(CH3)2), 98.8 (C-2), 74.9 (C-
7), 72.9 (C-5), 72.7 (C-6), 71.2 (C-4), 67.6 (C-8), 50.8 (OCH3), 33.5
(C-3), 27.2 (C(CH3)2), 26.2 (C(CH3)2), 25.9 (C(CH3)2), 25.1
(C(CH3)2); HRMS (FAB) calcd m/z for C15H24O8Na (M + Na+)
355.1363, found 355.1368.
chromatography. Data for 29β: Rf 0.22 (EtOAc/hexane 3:7); [α]25
D
1
+4.3 (c 0.3, CH2Cl2); H NMR (400 MHz, acetone-d6) δ 7.50−7.45
(m, 2H, H-2_MBn + H-6_MBn), 7.42−7.16 (m, 15H, Ar−H_OBn),
6.91−6.85 (m, 2H, H-3_MBn + H-5_MBn), 4.93 (d, 1H, J = 11.2 Hz,
CH2_Bn), 4.78−4.72 (m, 3H, CH2_OBn + H-1_Glc), 4.72−4.70 (m,
2H, CH2_OBn), 4.46 (d, 1H, J = 11.0 Hz, CH2_OBn), 4.41−4.29 (m,
2H, H-3 + H-6_Man), 4.24−4.15 (m, 2H, H-7b + H-4_Man), 4.04
(dd, 1H, J = 6.3, 8.5 Hz, H-7a_Man), 3.90 (dd, 1H, J = 1.8, 10.2 Hz,
H-6b_Glc), 3.82 (m, 1H, H-3_Glc), 3.77 (s, OCH3_Man), 3.73−3.65
(m, 2H, H-5_Man + H-5_Glc), 3.46 (dd, 1H, J = 3.6, 9.7 Hz, H-
2_Glc), 3.40−3.34 (m, 4H, OCH3_Glc + H-4_Man), 3.26 (dd, 1H, J
= 5.5, 10.2 Hz, H-6a_Glc), 2.28 (m, 2H, H-2b + H-2a), 1.49 (s, 3H,
C(CH3)2), 1.36 (s, 3H, C(CH3)2), 1.31 (s, 3H, C(CH3)2), 1.28 (s,
3H, C(CH3)2); 13C NMR (100 MHz, Acetone-d6) δ 160.5 (C-
4_MBn_Man), 147.4, 140.4, 140.0, 139.95, 133.6, 129.2 (C-2_MBn +
C-6_MBn_Man), 129.1, 129.0, 128.63, 128.61, 128.6, 128.4, 128.1,
114.5 (C-3_MBn + C-5_MBn_Man), 109.4 (C(CH3)2_Man), 109.2
(C(CH3)2_Man), 101.3 (C-1_Man), 98.3 (C-1_Glc), 83.0 (C-3_Glc),
81.3 (C-2_Glc), 79.1 (C-4_Glc), 76.5 (C-6_Man), 75.9 (CH2_Bn),
75.2 (CH2_Bn), 73.3 (C-5_Man), 72.9 (CH2_Bn), 72.4 (C-4_Man),
71.9 (C-3_Man), 70.9 (C-5_Glc), 67.0 (C-7b_Man), 62.1 (C-6_Glc),
55.6 (OCH3_Man), 55.1 (OCH3_Glc), 37.7 (C-2_Man), 27.6
(C(CH3)2_Man), 27.0 (C(CH3)2_Man), 26.1 (C(CH3)2_Man), 25.7
(C(CH3)2_Man); HRMS (FAB) calcd m/z for C48H58O12Na (M +
Na+) 849.3821, found 849.3810. Anal. Calcd for C48H58O12: C, 69.71;
H, 7.70. Found: C 69.63; H, 7.54. Data for 29α: Rf 0.35 (EtOAc/
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all synthesized compounds and X-
ray crystallographic data for compounds 14, 15, and 17 (CIF).
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Fax: (+1) 403 289-9488. E-mail: ccling@ucalgary.ca.
■
hexane 3:7); [α]25 +11.7 (c 0.6, CH2Cl2); 1H NMR (400 MHz,
D
ACKNOWLEDGMENTS
acetone-d6) δ 7.46−7.42 (m, 2H, H-2_MBn + H-6_MBn), 7.42−7.00
(m, 15H, Ar−H_OBn), 6.96−6.88 (m, 2H, H-3_MBn + H-5_MBn),
4.95 (d, 1H, J = 11.2 Hz, CH2_Bn), 4.87−4.67 (m, 5H, 2 × CH2
_OBn + H-1_Glc), 4.49 (ddd, 1H, J = 5.8, 5.9, 7.0 Hz, H-3_Man),
4.44−4.36 (m, 2H, H-6_Man +1H_OBn), 4.24 (dd, 1H, J = 2.4, 5.9
Hz, H-4_Man), 4.18 (dd, 1H, J = 2.5, 7.0 Hz, H-5_Man), 4.16−4.11
(m, 2H, H-7b + H-7a_Man), 3.90−3.79 (m, 4H, H-3_Glc +
OCH3_Man), 3.69 (ddd, 1H, J = 2.0, 7.4, 9.7 Hz, H-5_Glc), 3.52
(dd, 1H, J = 3.6, 9.6 Hz, H-2_Glc), 3.38 (s, 3H, OCH3_Glc), 3.36−
3.19 (m, 3H, H-6b + H-6a + H-4_Glc), 2.26 (dd, 1H, J = 5.9, 13.9 Hz,
H-2b_Man), 1.80 (dd, 1H, J = 8.1, 13.9 Hz, H-2a_Man), 1.35 (s, 3H,
C(CH3)2), 1.32 (s, 6H, C(CH3)2), 1.26 (s, 3H, C(CH3)2); HRMS
(FAB) calcd m/z for C48H58O12Na (M + Na+) 849.3821, found
849.3811.
■
We thank the Natural Sciences and Engineering Research
Council of Canada, the Canadian Foundation for Innovation,
and the Government of Alberta for the support of this project.
REFERENCES
■
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1H, J = 5.5, 5.5, 6.5 Hz, H-4), 4.34−4.21 (m, 3H, H-7 + H-8b + H-5),
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