Ring expansion of oxyglycals. Synthesis and conformational analysis of septanoside-containing trisaccharides

Article abstract of DOI:10.1021/jo901945e

(Chemical Equation Presented) Oxyglycals, derived from lactose and maltose, were expanded to trisaccharides through a ring expansion method. Trisaccharides with 6-7-5 and 6-7-6 ring sizes were prepared through the ring expansion method, with high diastereoselectivities, in each step of their synthesis. The NOE and ROESYNMR spectroscopies were used to assess the dipolar couplings within the trisaccharide. A computational study was undertaken, from which low energy conformations, as well as, dihedral angles that define the glycosidic linkages were identified. 2009 American Chemical Society.

Full text of DOI:10.1021/jo901945e

pubs.acs.org/joc
constitute the ring system, are (i) the intramolecular nitrone
Ring Expansion of Oxyglycals. Synthesis and
Conformational Analysis of Septanoside-Containing
Trisaccharides
cycloaddition involving appropriately nitrone and olefin-
functionalized acyclic precursors6 and (ii) metal-catalyzed
cyclizations of γ-allenols7 and alkynols.8 Ring-closing me-
tathesis reaction9 and cyclic hemiacetal formation10 are also
found to be useful in the construction of oxepanes. Septano-
side and oxepine formation through cyclization of acyclic
precursors leads to endo-cyclic participation of C-6 and the
attendant loss of exo-cyclic hydroxymethyl group in many
occasions. On the other hand, ring-expansion strategies
involving glycals lead to C-2 deoxy-septanoses, requiring
additional synthetic manipulation of C-2. This limitation
of C-2 deoxy septanose formation through pyranose ring
expansion could be overcome in a facile manner through
utilizing oxyglycals. The method involving oxyglycals,
wherein an oxygen functionality resides at C-2 of glycals,
formed the focus of our efforts to synthesize septanoses and
septanosides.11 The oxyglycals are subjected to a cyclopro-
panation, followed by a nucleophilic ring-opening, leading
to C-2 and C-3 functionalized oxepines. The ring-opening of
cyclopropanated oxyglycals is stereoselective generally, lead-
ing to R-substituted oxepines.11a However, a loss in stereo-
selectivity could be noticed when phenoxides were used.11b
On the other hand, alkoxides derived from sugars formed
oxepines, with concomitant formation of the glycoside bond
at C-1. Following initial observation of the use of sugars, we
undertook the synthesis trisaccharides incorporated with
septanoside residues. Following synthesis, efforts to identify
conformational features of the new trisaccharides, with the
aid of NMR spectroscopy and computational methods, were
undertaken. Synthesis and studies of septanoside containing
trisaccharides are reported herein.
N. Vijaya Ganesh,† S. Raghothama,‡ R. Sonti,‡ and
N. Jayaraman*,†
†Department of Organic Chemistry and ‡NMR Research
Centre, Indian Institute of Science, Bangalore 560 012, India
jayaraman@orgchem.iisc.ernet.in
Received September 9, 2009
Oxyglycals, derived from lactose and maltose, were
expanded to trisaccharides through a ring expansion
method. Trisaccharides with 6-7-5 and 6-7-6 ring sizes
were prepared through the ring expansion method, with
high diastereoselectivities, in each step of their synthesis.
The NOE and ROESY NMR spectroscopies were used to
assess the dipolar couplings within the trisaccharide. A
computational study was undertaken, from which low
energy conformations, as well as, dihedral angles that
define the glycosidic linkages were identified.
Synthesis. Syntheses of hepta-O-benzyl-protected oxy-
2 and hepta-O-benzyl-protected oxymaltal 5
lactal
were initiated from D-lactose and D-maltose, respectively.
The protected lactose derivative 1 was synthesized
through procedures known previously.12 Chlorination of
1, using SOCl2 and DMF, followed by a dehydrohalogena-
tion, in the presence of DBU/Et3N in CH3CN, afforded
Seven-membered cyclic sugars, namely, septanoses are
unnatural sugars. Although reports on identification
of septanoses could be traced back to early work of Stevens
in the 1970s,1 elaborate synthetic methods and studies
appeared much later. Notable advancements in the synthesis
of septanoses in recent years are (i) the ring-expansion
strategies of Hoberg2 and Nagarajan3 on 1,5-anhydrohex-
1-enitols, namely, glycals and (ii) ring-closing metathesis
reaction of suitably functionalized acyclic diene precursors
of van Boom and co-workers4 and Peczuh and co-workers.5
Few methods that describe formation of seven-membered
oxepane ring systems, wherein one or more deoxy carbon(s)
(6) (a) Tripathi, S.; Roy, B. G.; Drew, M. G.; Mandal, S. B. J. Org. Chem.
2007, 72, 7427–7430. (b) Al-Harrasi, A.; Reissig, H.-U. Angew. Chem., Int.
Ed. 2005, 44, 6227–6231.
´
(7) Alcaide, B.; Almendros, P.; Martınez del Campo, T. Angew. Chem.,
Int. Ed. 2007, 46, 6684–6687.
(8) Boone, M. A.; McDonald, F. E.; Lichter, J.; Lutz, S.; Hardcastle, K. I.
Org. Lett. 2009, 11, 851–854.
(9) (a) DeMatteo, M. P.; Snyder, N. L.; Morton, M.; Hadad, C. M.;
Peczuh, M. W. J. Org. Chem. 2005, 70, 24–38. (b) Schmidt, B.; Biernat, A.
Chem.;Eur. J. 2008, 14, 6135–6141. (c) Jadhav, V. H.; Bande, O. P.; Pinjari,
R. V.; Puranik, V. G.; Dhavale, D. D. J. Org. Chem. 2009, 74, 6486–6494.
(d) Wong, J. C. Y.; Lacombe, P.; Sturino, C. F. Tetrahedron Lett. 1999, 40,
8751–8754.
(1) (a) Stevens, J. D. Chem. Commun. 1969, 1140–1141. (b) Stevens, J. D.
Carbohydr. Res. 1972, 21, 490–492.
(10) (a) Johnson, C. R.; Golebiowski, A.; Steensma, D. H. J. Am. Chem.
€
Soc. 1992, 114, 9414–9418. (b) Tauss, A.; Steiner, A. J.; Stutz, A. E.;
(2) (a) Hoberg, J. O.; Bozell, J. J. Tetrahedron Lett. 1995, 36, 6831–6834.
(b) Cousins, G. S.; Hoberg, J. O. Chem. Soc. Rev. 2000, 29, 165–174.
(3) Ramana, C. V.; Murali, R.; Nagarajan, M. J. Org. Chem. 1997, 62,
7694–7703.
Tarling, C. A.; Withers, S. G.; Wrodnigg, T. M. Tetrahedron: Asymmetry.
2006, 17, 234–239. (c) Sizun, G.; Dukhan, D.; Griffon, J.; Griffe, L.;
Meillon, J.; Leroy, F.; Storer, R.; Gosselin, G. Carbohydr. Res. 2009, 344,
448–453.
(4) Ovaa, H.; Leeuwenburgh, M. A.; Overkleeft, H. S.; van der Marel,
G. A.; van Boom, J. H. Tetrahedron Lett. 1998, 39, 3025–3028.
(5) (a) Peczuh, M. W.; Snyder, N. L. Tetrahedron Lett. 2003, 44, 4057–
4061. (b) Castro, S.; Fyvie, S.; Hatcher, S. A.; Peczuh, M. W. Org. Lett. 2005,
21, 4709–4712.
(11) (a) Ganesh, N. V.; Jayaraman, N. J. Org. Chem. 2007, 72,
5500–5504. (b) Ganesh, N. V.; Jayaraman, N. J. Org. Chem. 2009, 74,
739–746.
(12) (a) Tsuzuki, M.; Tsuchiya, T. Carbohydr. Res. 1998, 311, 11–24.
(b) Ishii, K.; Kubo, H.; Yamasaki, R. Carbohydr. Res. 2002, 337, 11–20.
DOI: 10.1021/jo901945e
r
Published on Web 12/07/2009
J. Org. Chem. 2010, 75, 215–218 215
2009 American Chemical Society

Ganesh et al.
JOCNote
SCHEME 1
SCHEME 4
SCHEME 2
signals at 95.3 and 99.9 ppm for R-gluco- and chloro-oxepine
units, respectively. HR-MS analysis further confirmed the
composition of 7 and 8.
SCHEME 3
The chloro-vinyl ether moiety in 7 and 8 were converted to
diols 9 and 10, through an oxidation, followed by a reduc-
tion. The reduction of diketo intermediate occurred with
high selectivity and a single diastereomer of partially pro-
tected septanosides 9 and 10 were obtained. The anomeric
proton of the septanoside unit in 9 and 10 resonated as a
doublet (∼4.9 ppm, J = 4.8 Hz), and the corresponding
carbon nucleus was observed at ∼99.8 ppm.
Synthesis of Septanosyl Trisaccharides. Appropriately
protected sugar alcohols 11 and 12 were used for ring
expansion of lactose derivative 3. Reaction of 3 with
11/12 (2 molar equiv) was carried out under reflux condi-
tions, in the presence of K2CO3 (15 molar equiv), in PhMe
for 4-5 days (Scheme 4). The ring expansion occurred with
both the sugars and the chloro-oxepine derived 6-7-5
trisaccharide 13 and 6-7-6 trisaccharide 14 were obtained,
in 51% and 45% yields, respectively. The ring-opening
occurred in a stereoselective manner and only the R-anom-
2,3,6-tri-O-benzyl-4-O-(2,3,4,6-tetra-O-benzyl-β-D-galacto-
pyranosyl)-1,5-anhydro-D-arabino-hex-1-enitol (2) (Scheme 1),
in a moderate yield. The 13C NMR spectrum showed peaks at
127.8 ppm and 138.6 ppm, for C-1 and C-2 of oxyglycal moiety
and 103.0 ppm for the anomeric carbon of β-galacto moiety,
respectively. Cyclopropanation of oxylactal 2 was conducted
using dichlorocarbene, prepared in situ by treatment of CHCl3
with aq NaOH, under phase-transfer conditions. The carbene
addition was effective and the cyclopropanated adduct 3 was
obtained as a single diastereomer. The 13C NMR spectrum of 3
showed a resonance at 63.6 ppm, corresponding to the newly
introduced carbon with two chloro substituents.
Hepta-O-benzyl-protected oxymaltal 5 was synthesized
similarly (Scheme 2) and the cyclopropanated disaccharide
6 formed in 75% yield. Dichloroadducts 3 and 6 were
subjected to ring-opening reactions, conducted with meth-
oxide initially. The solvolysis of 3 and 6 afforded chloro-
oxepines 7 and 8 (Scheme 3). The reaction was sluggish with
6, and only 38% yield of 8 was obtained after 5 days of
reaction. It is likely that the cyclopropane moiety in 6 is more
hindered due to an R-orientation of the nonreducing end
sugar attached at C-4. Also the reaction was conducted for
prolonged duration, a mixture of polar products was identi-
fied, in addition to the chloro-oxepine product. Efforts to
isolate and identify the products were unsuccessful.
1
ers formed. The H NMR spectra of 13 and 14 showed a
singlet at ∼5.5 ppm for the anomeric proton of chloro-
oxepine sugar unit. Mass spectral analysis further con-
firmed the composition. Subsequent oxidation and reduc-
tion reactions were performed on 13 and 14. The NaBH4
reduction of diketo derivatives observed to occur with high
diastereoselectivities and a single diastereomer was ob-
tained (Scheme 4). Trisaccharides 15 and 16 were obtained
1
in moderate yields. In the H NMR spectra, H-1 of the
septanoside residue in 15 and 16 appeared as a doublet at
∼5.03 ppm (JH1-H2 ∼4.5 Hz), whereas 13C NMR spectrum
showed resonances at 107.1 ppm (R-arabino-), 105.4 ppm
(β-galacto-) and 100.1 ppm (R-septano-) for the anomeric
carbons of 15. Similarly, resonances at 105.5 ppm (β-galacto),
99.0 ppm (R-septano-), and 97.8 ppm (R-gluco-) were observed
for the anomeric carbons of 16.
The O-benzyl groups in 9, 10, 15, and 16 were deprotected
(Pd/C, H2) to afford the free septanoside-containing di- and
trisaccharides 17-20, respectively (Figure 1). Constitutions
of the deprotected sugars 17-20 were confirmed by NMR
spectroscopic and mass spectrometric techniques.
The ring-opening reaction of maltose-derived dichloro-
adduct 6 was conducted using sugars 11 and 12. Reactions
were found to be less effective and <10% conversion was
observed with both 11 and 12, even after several days under
reflux conditions.
Conformational Analysis. Upon synthesis of septanosyl
sugar-containing trisaccharides, an assessment of their con-
formational features, in terms of overall conformation and
The chloro-oxepine product formed stereoselectively, and
only the R-anomer was obtained. The C-1 nucleus in 7 was
observed at 100.7 ppm, along with a resonance at 105.5 ppm
for the anomeric carbon of the β-galacto moiety. The olefinic
carbons were ascertained from resonances at 121.4 and
1
152.7 ppm in 13C NMR spectrum of 7. In the H NMR
spectrum of 8, resonances of anomeric protons appeared as a
doublet (JH1-H2 = 3.6 Hz) and as a singlet (5.22 ppm, JH1-H2)
corresponding to R-gluco- and chloro-oxepine units, respec-
tively. Similarly, 13C NMR spectra showed anomeric carbon
216 J. Org. Chem. Vol. 75, No. 1, 2010

Ganesh et al.
JOCNote
FIGURE 1. Molecular structures of 17-20.
dihedral angles that define the glycosidic linkages, was
undertaken. The ring conformations of the septanoses
and oxepines were studied by Peczuh9a,13 and others.9c
With an objective to assess the lowest energy conforma-
tions of trisaccharides, the 6-7-6 trisaccharide 20 was
undertaken for the study, which included solution-state
and computational methods. The solution-state studies
were utilized to identify dipolar couplings. The computa-
tional method was utilized further to derive minimum
energy conformations. The solution-state conformational
analysis was performed with nuclear Overhauser spectros-
copy (NOE) and rotating-frame Overhauser spectroscopy
(ROESY). Prior to these experiments, structural assign-
ment of the proton signals was verified using double
quantum filtered correlated spectroscopy (DQF-COSY),
2D heteronuclear single quantum coherence (2D-HSQC)
and depolarization transfer (13C-DEPT) NMR techni-
ques. Unambiguous assignments were possible by follow-
ing the connectivities initiated with nonoverlapping
protons. From these, the rest of the protons could be
assigned, which facilitated analysis of subsequent dipolar
coupling patterns.
The NOE studies were conducted on 20 in D2O at
ambient temperature. Well-resolved signals of the 1H
NMR spectrum were subjected to NOE irradiations. Key
NOE enhancements were observed upon saturation of
Sep-H-1 and Gal-H-1. Similar enhancements were ob-
served upon irradiation of other protons. Further analysis
of the dipolar couplings was performed with the aid of
ROESY experiments. An examination of the ROESY
spectrum revealed the following significant correlations.
The Sep-H-1 nucleus showed strong cross peaks with H-6a
of the methyl pyranoside residues Sep-H-2 and Sep-H-7a.
Similarly, Gal-H-1 showed cross peaks with Gal-H-5, Sep-
H-4, and Sep-H-6 of the adjacent septanoside ring. A weak
cross peak between Gal-H-1 and Sep-H-7a was also ob-
served. Figure 2 summarizes distinct cross-peaks between
different protons in 20, as observed in NOE and ROESY
experiments.
FIGURE 2. Significant dipolar couplings observed in 20. Dihedral
angles (φ, Ψ, and ω) are given in Table 1. The observed hydrogen
bonding is shown as a dotted line.
FIGURE 3. Septanoside conformation of an optimized structure of
20, with labeling. The galactopyranoside portion is removed for
clarity. This structure represents conformation 3 of computational
studies (cf. the Supporting Information). The observed hydrogen-
bonding interaction is shown as a dotted line. Atoms involved in
hydrogen bonding are labeled.
with the AMBER* force field. This process led to identifying
114 unique conformers with <1 kcal mol-1 of global mini-
mum. Conformers with good convergence and with relative
energies <0.3 kcal mol-1 were taken for further optimizations
using B3LYP/6-31þG* level, at gas phase. Figure 3 shows the
septanoside conformation from an optimized structure of 20,
calculated with the above basis set. The septanoside adopted a
twist-chair conformation, in the O,1TC5,6 form, derived on the
basis that a coplanarity in the septanoside ring could be
observed only with C2-C3-C4 atoms. A contiguous positive
sign and remaining alternate positive and negative signs of
dihedral angles represented a twist-chair conformation. The
contiguous positive signs for C2-C3 and C3-C4 dihedral
angles within the ring denoted further the O,1TC5,6 conforma-
tion.15 The geometry of C6-C7 rotamers of septanoside was
found to be “gauche-trans”. A hydrogen-bonding interaction
between exocyclic hydroxymethyl group of septanoside and
endocyclic oxygen of glucopyranoside as well as sterically
unencumbered spatial disposition of the galactopyranoside
about the septanoside were observed. The conformation of
the trisaccharide herein differs from tthe 3,4TC5,6 conformation
identified for methyl R/β-D-septanosides studied by Peczuh
and co-workers.9a Substituent effects on septanoside and the
Molecular modeling study was undertaken subsequently in
order to identify energy-minimized conformations of 20.
Monte Carlo multiple search protocol, as implemented in
Macromodel (version 8.5),14 was used to generate a large pool
of conformers of 20. Spatial distances from NMR experiments
were incorporated before molecular dynamics were performed
(13) DeMatteo, M. P.; Mei, S.; Fenton, R.; Morton, M.; Hadad, C. M.;
Peczuh, M. W. Carbohydr. Res. 2006, 341, 2927–2945.
(14) Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.;
Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W. C. J. Comput.
Chem. 1990, 11, 440–467.
(15) Entrena, A.; Campos, J. M.; Gallo, M. A.; Espinosa, A. ARKIVOC
2005, 88–108.
J. Org. Chem. Vol. 75, No. 1, 2010 217

Ganesh et al.
JOCNote
TABLE 1. Glycosidic Linkage Dihedral Angles and Calculated Relative Energies for Three Lowest Energy Conformations of 20a
1f5 glycosidic linkage of Gal-Sep
1f6 glycosidic linkage of Sep-Glc
conformer
B3LYP/6-31þG* Erel (kcal/mol)
φ1
Ψ1
φ2
Ψ2
ω
1
3
5
0.245
0.00
1.73
-80.7
-79.9
-73.7
-155.3
-148.9
-147.2
83.8
83.0
82.1
-111.6
-109.7
-109.5
80.1
80.4
81.0
aφ1 = O5-C1-O1-C50; Ψ1 = C1-O1-C50-C60; φ2 = O60-C10-O10-C600, Ψ2 = C10-O10-C600-C500; ω = O10-C600-C500-O500. 1, 5; 10, 50, 60;
and 100, 500, 600 refer to carbons of Gal-; Sep-; and Glc-residues, respectively.
attendant intramolecular interactions appear to be the reasons
for the observed differences at present. The torsion angles
about the glycosidic linkages identified for a few conformers
after global minimizations are given in Table 1. Synclinal and
anticlinal arrangements are observed for the glycosidic bonds
involved with the septanoside sugar.
Oxyglycals as useful synthons for cyclopropanation and
ring expansion are exemplified herein with the synthesis of
trisaccharides, relating to galacto-septano-arabinofurano-
and galacto-septano-glucopyrano configurations. The synthe-
sis leads not only to a ring expansion but also a concomitant
glycoside formation in a stereoselective manner. Following
synthesis, distant constraints were assessed by NOE and
ROESY NMR spectroscopies. Conformational analysis
using computational methods showed O,1TC5,6 conforma-
tions for the septanoside.
diluted with EtOAc (20 mL) and CH2Cl2 (20 mL), filtered through
silica gel, and washed with EtOAc (2 ꢀ 20 mL), and the solvents
were removed in vacuo. The crude 2,3-diketo derivative in MeOH
(3 mL) was added with NaBH4 (0.008 g, 0.205 mmol) at 0 °C, the
mixture was stirred for 2 h, and solvents were removed in vacuo.
The residue was dissolved in EtOAc (30 mL), washed with brine
(20 mL), dried (Na2SO4), and concentrated in vacuo, and the crude
product was purified (hexane/EtOAc = 3:2), to afford diol 16
(0.065 g, 47%) as a colorless oil: Rf 0.65 (hexane/EtOAc = 1:1);
1
[R]24 þ29.3 (c 1.00, CHCl3); H NMR (300 MHz, CDCl3) δ
D
7.38-7.18 (m, 45H), 5.04 (d, J = 4.2 Hz, 1H), 4.92 (dd, J = 11.1,
8.1 Hz, 2H), 4.77-4.64 (m, 8H), 4.60-4.47 (m, 5H), 4.43-4.23
(m, 5H), 4.14-4.01 (m, 4H), 3.96-3.91(m, 2H), 3.86 (app.s, 1H),
3.76-3.65 (m, 4H), 3.61-3.47 (m, 3H), 3.44-3.30 (m, 8H); 13C
NMR (75 MHz, CDCl3) δ 139.3, 138.8, 138.5, 138.4, 138.2, 138.1,
137.9, 137.8, 128.4, 128.2, 128.1, 127.9, 127.8, 127.5, 127.4, 127.3,
127.2, 105.5, 99.0, 97.8, 82.7, 82.3, 81.9, 80.3, 79.7, 79.3, 77.9, 75.6,
75.2, 74.9, 74.7, 73.6, 73.5, 73.4, 73.3, 73.2, 73.0, 72.9, 71.5, 71.3,
69.8, 69.6, 68.6, 67.8, 55.2; HRMS m/z C83H90O17Na calcd
1381.6076, found 1381.6137.
Experimental Section
Methyl O-(2,3,4,6-Tetra-O-benzyl-β-D-galactopyranosyl)-
(1f5)-(2-chloro-2-deoxy-3,4,7-tri-O-benzyl-r-D-arabino-hept-
2-enoseptanosyl)-(1f6)-2,3,4-tri-O-benzyl-r-D-glucopyranoside (14).
A solution of alcohol 12 (0.54 g, 1.15 mmol) in PhMe (1 mL) was
added to a stirring mixture of 3 (0.6 g, 0.58 mmol), K2CO3 (1.2 g,
8.6 mmol), and 18-C-6 (0.046 g, 0.17 mmol) in PhMe (4 mL)
and the mixture refluxed for 5 days. The reaction mixture was
filtered over Celite, and solvents were removed in vacuo.
The residue was purified (hexane/EtOAc = 8:2) to afford 14
(0.381 g, 45%) as a colorless oil: Rf 0.30 (hexane/EtOAc = 4:1);
1H NMR (300 MHz, CDCl3) δ 7.34-7.19 (m, 50H), 5.55 (s, 1H),
4.96-4.86 (m, 2H), 4.83-4.73 (m, 8H), 4.69-4.56 (m, 10H),
4.48 (d, J = 12 Hz, 1H), 4.42 (d, J = 12.1 Hz, 2H), 4.33-4.22
(m, 5H), 3.99-3.81 (m, 5H), 3.74-3.65 (m, 2H), 3.61-3.55 (m,
2H), 3.50-3.32 (m, 2H), 3.34 (s, 3H); 13C NMR (75 MHz,
CDCl3) δ 152.4, 138.9, 138.8, 138.5, 138.3, 138.2, 137.8, 137.2,
128.4, 128.3, 128.2, 128.1, 128.0, 127.8, 127.6, 127.5, 127.4,
127.3, 121.8, 105.6, 99.6, 97.8, 82.7, 82.1, 81.9, 80.2, 78.9, 78.7,
78.0, 75.6, 75.2, 74.9, 74.6, 73.4, 73.3, 73.0, 72.9, 72.7, 71.8, 71.5,
71.0, 70.9, 67.9, 66.1, 55.1; HRMS m/z C90H93ClO16NH4 calcd
1482.6496, found 1482.6548.
Methyl O-(β-D-Galactopyranosyl)-(1f5)-(r-D-glycero-D-galacto-
septanosyl)-(1f6)-r-D-glucopyranoside (20). A solution of diol 16
(0.037 g, 0.027 mmol) in MeOH (3 mL) was added with Pd/C
(10%, 0.015 g), and the mixture was stirred under a positive
pressure of H2 gas for 48 h. The reaction mixture was filtered
over Celite and washed with MeOH (2 ꢀ 20 mL), and solvents
were removed in vacuo to afford 20 (0.013 g, 88%) as a white
foam: Rf 0.24 (CHCl3/CH3OH = 3:2); [R]24 þ87.0 (c 1.00,
D
MeOH); 1H NMR (700 MHz, D2O) δ 5.0 (d, J = 4.0 Hz, 1H),
4.82 (d, J = 4.0 Hz, 1H), 4.50 (d, J = 7.7 Hz, 1H), 4.22 (d, J =
6.3 Hz, 1H), 4.15 (dd, J = 7.7, 2.1 Hz, 1H), 4.12-4.05 (m, 2H),
3.93 (d, J = 2.8 Hz, 1H), 3.90-3.79 (m, 6H), 3.77-3.73 (m, 2H),
3.68-3.64 (m, 2H), 3.61-3.54 (m, 4H), 3.43 (s, 3H); 13C NMR
(75 MHz, D2O) δ 104.7, 100.3, 98.1, 81.2, 76.2, 74.0, 73.5, 72.0,
71.8, 71.3, 71.0, 70.5, 70.4, 69.5, 62.9, 62.0, 56.0; HRMS m/z
C20H36O17Na calcd 571.1850, found 571.1862.
Acknowledgment. We thank the Department of Science
and Technology, New Delhi, for financial support. The
Council of Scientific and Industrial Research, New Delhi,
is acknowledged for a research fellowship to N.V.G.
Methyl O-(2,3,4,6-Tetra-O-benzyl-β-D-galactopyranosyl)-(1f5)-
(4,7-di-O-benzyl-r-D-glycero-D-galacto-septanosyl)-(1f6)-2,3,4-tri-
O-benzyl-r-D-glucopyranoside (16). A solution of RuCl3 3H2O
Supporting Information Available: General experimental
procedure, 1H and 13C NMR spectral data of all new com-
pounds, methods, and results of NMR and computational
studies. This material is available free of charge via the Internet
at http://pubs.acs.org.
3
(0.002 g, 0.007 mmol) and NaIO4 (0.028 g, 0.13 mmol) in water
(0.8 mL) was added dropwise to a solution of chloro-oxepine 14
(0.15 g, 0.102 mmol) in MeCN/EtOAc (5 mL, 1:1), at 0 °C. After
24 h of stirring at room temperature, the reaction mixture was
218 J. Org. Chem. Vol. 75, No. 1, 2010