Synthesis, crystal structure, and reactivity of a D-xylose based oxepine

Article abstract of DOI:10.1016/j.carres.2004.01.022

The synthesis and X-ray crystal structure of a D-xylose-based oxepine (9) are reported. The oxepine was prepared from 2,3,4-tri-O-benzyl-D-xylose by the three-step sequence (Wittig olefination, vinyl ether formation, and ring closing metathesis) we recently reported. Epoxidation of this cyclic enol ether (9) using dimethyldioxirane (DMDO) gave 1,2-anhydro-β-D-idoseptanose (10), which was trapped by a number of nucleophiles to give α-idoseptanosides. The stereochemistry of epoxidation was assigned based on product analysis. Spectroscopic data of methyl 2,3,4,5-tetra-O-acetyl-α-D-idoseptanoside, derived from the methanolysis product 11, was compared to data of its enantiomer, the known methyl 2,3,4,5-tetra-O-acetyl-α-L-idoseptanoside.

Full text of DOI:10.1016/j.carres.2004.01.022

Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 1163–1171
Synthesis, crystal structure, and reactivity
of a
D
-xylose based oxepine
Mark W. Peczuh,* Nicole L. Snyder and W. Sean Fyvie
Department of Chemistry, The University of Connecticut, 55 North Eagleville Road, Storrs, CT 06269, USA
Received 6 November 2003; accepted 29 January 2004
Abstract—The synthesis and X-ray crystal structure of a
2,3,4-tri-O-benzyl- -xylose by the three-step sequence (Wittig olefination, vinyl ether formation, and ring closing metathesis) we
recently reported. Epoxidation of this cyclic enol ether (9) using dimethyldioxirane (DMDO) gave 1,2-anhydro-b- -idoseptanose
(10), which was trapped by a number of nucleophiles to give a-idoseptanosides. The stereochemistry of epoxidation was assigned
based on product analysis. Spectroscopic data of methyl 2,3,4,5-tetra-O-acetyl-a- -idoseptanoside, derived from the methanolysis
D-xylose-based oxepine (9) are reported. The oxepine was prepared from
D
D
D
product 11, was compared to data of its enantiomer, the known methyl 2,3,4,5-tetra-O-acetyl-a-
Ó 2004 Elsevier Ltd. All rights reserved.
L-idoseptanoside.
Keywords: Septanose carbohydrates; Oxepine;
D-Idoseptanoside; Glycosylation
1. Introduction
idoseptanose (10) stereoselectively; the anhydrosepta-
nose was then trapped by a number of nucleophiles to
give the corresponding septanosides.
Septanoses, or seven-membered ring sugars are homo-
logs of pyranoses. Their similarity to natural carbohy-
drates suggests that they should have interesting and
potentially useful physical, chemical, and biological
properties. There are many examples of hydroxylated
oxepines in fused polycyclic marine natural products,
but no natural seven-membered ring carbohydrates are
known.1 Septanose carbohydrates are conceptually
similar to homologated versions of nucleic acids and
protein monomers. Such oligomers of these monomers
have provided new unnatural structures and interesting
biological activity.2 The synthesis and conformational
analysis of septanose carbohydrates has received only
limited attention however. Here we report the synthesis,
X-ray crystal structure, and chemical reactivity of
O
O
O
O
HO
O
O
OCH3
O
O
O
O
1
2
AcO
O
O
O
AcO
O
AcO
O
O
OAc
O
3
An initial challenge to the systematic investigation of
septanose structure and function is the identification of
general synthetic routes for their preparation. For
example, Stevens and co-workers3–7 have made consid-
erable progress in the preparation of mono-septanosides
that correspond to the natural aldohexoses. Treatment
an oxepine derived from 2,3,4-tri-O-benzyl-
Specifically, 1,6-anhydro-3,4,5-tri-O-benzyl-2-deoxy-
xylosept-1-enitol (9) was treated with dimethyldioxirane
(DMDO) to give 3,4,5-tri-O-benzyl-1,2-anhydro-b-
D-xylose.
D
-
D
-
of
acetone–methanol forms 1,2;3,4-di-O-isopropylidene-
a-
-glucoseptanose (1)3 and methyl 2,3;4,5-di-O-iso-
propylidene-a-
-glucoseptanoside (2),4 respectively.
D-glucose with either acidified acetone or acidified
D
* Corresponding author. Fax: +1-860-486-2981; e-mail: mark.
peczuh@uconn.edu
D
0008-6215/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.01.022

1164
M. W. Peczuh et al. / Carbohydrate Research 339 (2004) 1163–1171
Selective refunctionalization of 1 and 2 have given
-altro-,6 -gulo-,6 and -galacto-6 derivatives. Preferred
L
-ido-,5
a
O
OR
BnO
BnO
BnO
BnO
L
D
D
OH
BnO
BnO
conformations of these derivatives have been described
in both solution and solid state.3–7 A general preparation
of pyranosyl septanosides has been reported by McAu-
liffe and Hindsgaul.8 Acceptors were glycosylated by
acyclic chloro-thioethyl acetals to give mixed O,S ace-
tals. The primary alcohol of the acyclic donor was then
selectively deprotected and cyclized using a thiophilic
promoter to give pyranosyl septanosides such as 3.
Other synthetic strategies for seven-membered ring
monosaccharides have also been reviewed.9
We endeavored to utilize the known transformations
of glycals (4)10 in the preparation of septanose carbo-
hydrates from oxepines (5). Toward this end, we have
recently reported a concise synthetic preparation of
oxepines from protected pyranoses.11 Here we describe
in detail the synthesis of an oxepine using 2,3,4-tri-O-
R = H (7)
R = (8)
6
b
c
O
BnO
BnO
BnO
9
Scheme 1. Reagents and conditions: (a) n-BuLi, CH2@P(Ph)3, THF
(63%), (b) Pd(OAc)2, 1,10-phenanthroline, CH2@CHOEt, CH2Cl2
40 °C (90%), (c) 2,6-diisopropylphenylimidoneophylidenemolybde-
num(VI) bis(hexafluoro-t-butoxide) (Schrock catalyst) 20 mol %,
CH3Ph (85%).
Oxepine 9, a white solid, was recrystallized from
petroleum ether to give crystals suitable for X-ray
analysis. The molecular structure of 9 (Fig. 1) showed
that it is in a slightly distorted twist chair (TC). It most
closely resembled a 6;OTC4;5 conformation.15 The devi-
ation from the TC conformation is presumably due to
the shortened planar C-1–C-2 (C-6–C-5 in ORTEP
numbering) bond. The O–C-6–C-5–C-4 (ORTEP num-
bering) unit, which includes the enol ether functionality
is nearly co-planar, with a dihedral angle about the C-1–
C-2 bond of 6.3°. Selected crystal and structural refine-
ment data are given in Table 1.
benzyl-D-xylose (6) as starting material. We report the
crystal structure of oxepine 9 and its oxidative coupling
with a number of nucleophiles using DMDO as an
electrophilic promoter. The results demonstrate the
chemical similarity between carbohydrate-based oxe-
pines and glycals and suggest that the synthesis of
septanose oligosaccharides should be possible.
OBn
OBn
O
O
BnO
BnO
BnO
BnO
BnO
4
5
2.2. Stereoselective oxidation of9 using dimethyldi-
oxirane (DMDO)
2. Results and discussion
The mild oxidizing agent DMDO has been used exten-
sively to convert glycals into 1,2-anhydro sugars that
serve as glycosyl donors when exposed to nucleo-
philes.10a For glycals, epoxide formation anti relative to
the benzyloxy substituent at C-3 has been most often
2.1. Synthesis and X-ray crystal structure ofoxepine (9)
The preparation of 9 followed a new procedure we re-
cently developed for converting protected pyranoses to
the corresponding oxepine using a ring-closing meta-
thesis (RCM) strategy.11 2,3,4-Tri-O-benzyl-
D-xylose (6)
was treated sequentially with n-butyllithium and meth-
ylene triphenylphosphane to give heptenitol (7) (Scheme
1) in 63% yield.12 The resulting hydroxyl group was then
converted to the vinyl ether 8 using Pd(OAc)2 and 1,10-
phenanthroline in the presence of ethyl vinyl ether
(90%).13 The RCM conditions were changed slightly
relative to the original report. The initial procedure
called for addition of Schrock catalyst14 to a solution of
the diene in toluene followed by heating to 60 °C for 4 h.
The new conditions changed only the temperature of the
reaction. Schrock catalyst was added to 8 in toluene and
stirred at room temperature for 2 h. The revised proce-
dure gave oxepine 9 in 85% yield relative to 82% for the
original procedure.11 The overall yield of 9 over three
steps was 48%.
Figure 1. ORTEP diagram of 1,6-anhydro-3,4,5-tri-O-benzyl-2-deoxy-
D
-xylosept-1-enitol (9).

M. W. Peczuh et al. / Carbohydrate Research 339 (2004) 1163–1171
1165
Table 1. Crystal data and structure refinement for 9
septanoside isomers 11 and 12 in a 4:1 ratio. The major
isomer (11) was subjected to hydrogenolysis conditions
and subsequently protected as the peracetate to give
Empirical formula
Formula weight
Temperature
C27H28O4
416.49
183(2) K
methyl 2,3,4,5-tetra-O-acetyl-a-D-idoseptanoside (13)
ꢀ
0.71073 A
Wavelength
(80% over two steps). Comparison of the 3JH1;H2 (6.5 Hz)
Crystal system
Space group
Unit cell dimensions
Monoclinic
P2
and ½aŠ þ79.8 (c 1.53) values of 13 with those recently
D
ð1Þ
ꢀ
ꢀ
reported for methyl 2,3,4,5-tetra-O-acetyl-a-L-idosept-
a ¼ 11:512ð2Þ A a ¼ 90°
anoside (14)5c (6.46 Hz, À85.1°, c 1.03) indicated that they
b ¼ 4:5899ð9Þ A b ¼ 94:97ð3Þ°
ꢀ
c ¼ 21:155ð4Þ A c ¼ 90°
were enantiomers. A sample of methyl a-L-idoseptano-
side supplied by Stevens was acetylated to give 14. In our
3
ꢀ
1113.6(4) A
Volume
Z
Density (calculated)
Absorption coefficient
F (0 0 0)
2
hands, 14 gave 3JH1;H2 of 6.5 Hz and ½aŠ À75.5 (c 1.78).
1.242 g/cm3
D
0.82 cmÀ1
These data secured the identity of 10 as 1,2-anhydro-
3,4,5-tri-O-benzyl-b-D-idoseptanose. The minor product
444
Crystal size
Theta range for data
Index ranges
0:35 ꢀ 0:10 ꢀ 0:05 mm3
1.95–28.35°
À15 <¼ h <¼ 15,
À5 <¼ k <¼ 5,
À28 <¼ l <¼ 27
4279
of methanolysis of 10 was assigned as structure 12,
based on spectroscopic data, the high selectivity of
epoxidation evidenced by the NMR data for 10, and the
highly selective formation of a-septanosides by other
nucleophiles (see later). We propose that 12 arose by
formation of an oxonium ion and subsequent b-attack
by methanol.
Reflections collected
Independent reflections
4279 [RðintÞ ¼ 0:0000]
Completeness to theta ¼ 28.35° 93.8%
Absorption correction
Max & min transmiss.
Refinement method
None
0.9959 and 0.9718
Full-matrix least-squares on F2
4279/1/280
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I > 2rðIÞ]
R indices (all data)
Absolute structure parameter
Largest diff. peak and hole
OCH
OCH
O
O
3
3
1.041
R1 ¼ 0:0512, wR2 ¼ 0:1159
R1 ¼ 0:0915, wR2 ¼ 0:1336
0.3(12)
OAc
OAc
OAc
OAc
AcO
AcO
AcO
AcO
À3
ꢀ
0.158 and À0.173 eA
14
13
O
O
a
2.3. Addition ofnucleophiles to 1,2-anhydro-3,4,5-tri-O-
benzyl-b- -idoseptanose (10)
BnO
BnO
9
D
BnO
10
OCH
OH
3
OH
O
b
O
Table 2 collects the results from the addition of several
nucleophiles to 1,2-anhydroseptanose 10. All reactions
that use 10 as a glycosyl donor were conducted as a two-
step sequence; 9 was epoxidized to 10 using DMDO,
then exposed to the nucleophile under the conditions
noted. Similar to the reaction of 10 with methanol, the
BnO
BnO
BnO
BnO
BnO
BnO
OAc
OCH
3
12
11
O
c
AcO
AcO
AcO
OCH
3
13
addition of 1,2:3,4-di-O-isopropylidene-a-D-galactopyr-
anose gave two septanosides, 15 and 16 (Fig. 2) in 45%
yield with a a/b ratio of 3:2. Addition of 2-propanol or
ethanethiol17 gave exclusively the a-septanosides 17 and
18 in 69% and 32% yields, respectively. All of the above
reactions were either under protic or Lewis acidic con-
ditions. We suspected that these reaction conditions may
have facilitated oxonium ion formation that resulted in
the a/b mixtures in entries 1 and 2. The occurrence of
anomeric mixtures in these cases suggested that the
thermodynamic stabilities of the a- and b-septanosides
may be similar; the specific collection of factors that
contribute to their respective energies are expected to be
difficult to rationalize. Toward this end, we are currently
using a combination of computational and spectro-
scopic methods to investigate the low energy confor-
mations of septanose carbohydrates.
Scheme 2. Reagents and conditions: (a) DMDO, CH2Cl2, 0 °C, (b)
CH3OH (60%, two steps) 11–12 4:1, (c) (i) H2, 10% Pd/CCH3OH; (ii)
Ac2O, pyridine (80%, two steps).
observed.16 Epoxidation of 9 was conducted using
DMDO in dry dichloromethane (CH2Cl2) (Scheme 2) at
0 °C over 0.5 h. Observation of the 1,2-anhydrosepta-
nose species by NMR indicated selective formation
(>25:1) of one epoxide. The spectroscopic data were not
able to rigorously define the stereochemistry of the
epoxide. Rather, spectroscopic data from a methyl
septanoside derived from this epoxide was compared to
a literature compound.
Specifically, epoxidation of 9 followed by exposure to
methanol gave a 60% yield of a mixture of two methyl

1166
M. W. Peczuh et al. / Carbohydrate Research 339 (2004) 1163–1171
Table 2. Reactions of various nucleophiles with 1,2-anhydroseptanose 10
Entry
Nucleophile
Conditions
Product(s)
Yield (%)
a=b
1
2
CH3OH
1,2;3,4-Di-O-isopropylidene-
CH3OH, rt
ZnCl2, THF, À78 °C to rt
11, 12
15, 16
60
45
4:1
3:2
a-D-galactopyranose
3
4
5
6
7
8
(CH3)2CHOH
CH3CH2SH
NaOCH3
AllylMgBr
NaN3
(CH3)2CHOH, rt
TFAA, À78 °C
CH3OH, rt
17
18
11
19
20
21
69
32
89
33
69
73
a
a
a
a
a
a
THF, À10 °C
aq DMF, rt
LiSPh
THF, 0 °C
OH
O
HO
O
O
O
O
BnO
BnO
BnO
BnO
O
O
BnO
O
O
BnO
O
O
O
O
15
16
O
O
OH
O
OH
OH
S
OH
OH
N
O
O
O
BnO
BnO
BnO
BnO
BnO
BnO
BnO
BnO
BnO
BnO
BnO
O
BnO
BnO
BnO
SCH CH
BnO
2
3
3
21
20
18
19
17
Figure 2. Septanoside products from nucleophilic attack on 1,2-anhydroseptanose 10.
Anionic additions to 1,2-anhydro sugars have been
reported previously.18 The addition of anionic nucleo-
3. Experimental
3.1. General methods
philes to 10 gave the a-septanosides 11, 19, 20, and 21
when using oxygen, carbon, nitrogen, and sulfur-based
nucleophiles (entries 5–8). The assignment of stereo-
chemistry for septanosides 17–21 was done based on the
similarity of their NMR spectral data to methyl sept-
anoside 11. Sodium methoxide addition to 10 cleanly
gave 11 in high yield (89%) confirming the selective
epoxidation of 9 and demonstrating the enhanced
nucleophilicity of anions. The efficiency in forming azido
septanoside 20 (69%) and thiophenyl septanoside 21
(73%) are noteworthy. First, azide 20 should be able to
be selectively functionalized (via reduction–acylation
sequence, for example) to supply new septanoside gly-
coconjugates. Access to 21 suggests that it too may be
used as a glycosyl donor in the preparation of additional
septanosides. In all the examples (11, 12, 15–21), the
C-2 alcohol can also be selectively functionalized.
In summary, we have demonstrated that 1,2-anhy-
droseptanoses such as 10, derived from oxepines can
serve as glycosyl donors in the preparation of septanose
carbohydrates. The reactivity demonstrated is directly
analogous to glycal chemistry. We have also gained
access to another class of glycosyl donor such as the
thiophenyl septanoside 21 via oxepine 9. Current efforts
are to evaluate the reactivity of oxepines such as 9 under
alternative reaction conditions in the synthesis of sep-
tanose carbohydrates.19
Unless stated otherwise, all reactions were conducted at
room temperature (rt) under nitrogen atmosphere. 3,4,5-
tri-O-benzyl-D-xylose was synthesized by the route of
Tsuda et al.20 Schrock catalyst was purchased from
Strem Chemicals (Newburyport, MA). DMDO was
generated as described in Ref. 21. Reactions were
ꢀ
monitored by TLC (silica gel, 60 A, F254, 250 lm).
Visualization was conducted either under UV light or by
charring with 2.5% p-anisaldehyde in H2SO4, AcOH,
and EtOH solution. Preparative chromatography was
ꢀ
conducted on silica gel (60 A, 32–63 lm, Sorbent Tech-
nologies, Atlanta, GA). Melting points are uncorrected.
Optical rotations were measured at 22 ꢁ 2 °C. 1H NMR
spectra were collected at 400 MHz with chemical shifts
referenced to (CH3)4Si (dH 0.00 ppm) or CHCl3 (dH
7.27 ppm). 13C NMR were collected at 100 MHz and
referenced to CDCl3 (dC 77.2 ppm).
3.2. 3,4,5-Tri-O-benzyl-1,2-dideoxy-D-xylohept-1-enitol
(7)
Into a flame dried round-bottom flask was added methyl
triphenylphosphonium bromide (4.46 g, 12.5 mmol) and
dry THF (30 mL) to make a white suspension, which
was cooled to 0 °C on an ice bath. n-Butyllithium

M. W. Peczuh et al. / Carbohydrate Research 339 (2004) 1163–1171
1167
(7.8 mL, 1.6 M) was added dropwise with stirring and
gave a clear, dark-orange solution of methylene triphe-
nylphosphane. This solution was stirred at 0 °C for
10 min, then allowed to warm to rt over 30 min. In a
separate flask, residual water was removed from 2,3,4-
H, J 14.3, 1.9 Hz), 4.01 (dd, 1 H, J 6.7, 1.9 Hz), 3.91 (m,
1 H), 3.85 (dd, 1 H, J 10.6, 4.2 Hz), 3.79 (dd, 1 H, J 10.5,
5.8 Hz), 3.69 (dd, 1 H, J 5.1, 5.1 Hz); 13C NMR (CDCl3)
d 151.7, 138.7, 138.6, 138.5, 134.6, 128.6, 128.4(2), 128.1,
128.0, 127.7(2), 118.9, 86.9, 81.4, 81.1, 77.8, 75.2, 73.2,
70.8, 68.1; FAB-MS m=z [MþH]þ calcd 445.2379, found
445.2401.
tri-O-benzyl-D-xylose (6) (1.50 g, 3.57 mmol) via
azeotropic distillation from toluene (3 ꢀ 15 mL) under
reduced pressure. The residue was dissolved in dry THF
(5 mL) and cooled to 0°C on an ice bath. n-Butyllithium
(2.2 mL, 1.6 M) was added dropwise with stirring. This
solution was then added to the methylene triphenyl-
phosphane solution via canula and stirred for 24–40 h.
The reaction was quenched by addition of aq NH4Cl
and the solvent was removed under reduced pressure.
The resulting orange oil was dissolved in CH2Cl2
(25 mL) and washed with brine (25 mL) and water
(25 mL). The organic layer was dried (Na2SO4) and the
solvent removed under reduced pressure. The residue
was purified by column chromatography, using 3:2
hexanes–EtOAc as eluent to give 7 (0.940 g, 63%) as a
3.4. 1,6-Anhydro-3,4,5-tri-O-benzyl-2-deoxy-D-xylosept-
1-enitol (9)
The following reaction was conducted in a glove box.
Diene 8 (0.485 g, 1.10 mmol) was dissolved in toluene
(195 mL). To this solution was added 2,6-di-
isopropylphenylimidoneophylidenemolybdenum(VI) bis-
(hexafluoro-t-butoxide) (Schrock catalyst) (0.168 g,
0.22 mmol) in toluene (5 mL). The mixture was stirred in
the glove box for 4 h, then removed from the box and
the solvent was removed under reduced pressure to give
a brown solid. Purification by column chromatography
using 4:1 hexanes–EtOAc gave 9 (0.389 g, 85%) as a
clear colorless oil. ½aŠ þ5.6 (c 2.43, CHCl3); IR (KBr)
D
cmÀ1 3447.13, 3063.37, 3029.62, 2870.52, 1496.49,
1454.06, 1209.15, 1064.51, 734.75, 697.14; 1H NMR
(CDCl3) d 7.38–7.32 (m, 15 H), 5.86 (ddd, 1 H, J 17.5,
10.5, 7.5 Hz), 5.30 (d, 1 H, J 7.5 Hz), 5.26 (s, 1 H), 4.72
(d, 1 H, J 11.7 Hz), 4.69 (d, 1 H, J 11.7 Hz), 4.57 (m, 4
H), 4.35 (d, 1 H, J 11.7 Hz), 4.18 (dd, 1 H, J 7.3, 4.1 Hz,
1) 3.68 (m, 3 H), 3.54 (d, 1 H, J 9,2 Hz); 13C NMR
(CDCl3) d 138.6, 138.5, 138.2, 135.3, 128.8, 128.6(3),
128.2, 128.1, 128.0, 127.9, 127.2, 119.1, 81.9, 80.6, 79.8,
75.0, 73.0, 70.9, 61.7; anal. calcd for C27H30O4: C, 77.48;
H, 7.22; O, 15.29; found C, 77.14; H, 6.93.
white solid. Mp 90–92 °C; ½aŠ þ2.7 (c 0.43, CHCl3); IR
D
(KBr) cmÀ1 3026.73, 2903.31, 2857.02, 1728.87, 1648.84,
1453.10, 1353.78, 1264.11, 1110.80, 1067.41, 733.78,
1
691.36; H NMR (CDCl3) d 7.35–7.26 (m, 15 H), 6.31
(d, 1 H, J 7.4 Hz), 4.86 (d, 1 H, J 11.2 Hz), 4.74–4.63 (m,
6H), 4.35 (dd, 1 H, J 12.9, 4.9 Hz), 4.27 (dd, 1 H, J 7.2,
3.4 Hz), 3.98 (d, 1 H, J 5.5 Hz) 3.96 (s, 1 H), 3.82 (dd, 1
H, J 4.5, 4.5 Hz); 13C NMR (CDCl3) d 157.5, 138.8,
138.6, 138.3, 128.6(2), 128.5, 128.2, 128.1, 127.9, 127.8,
104.2, 86.6, 82.8, 75.6, 74.6, 72.4, 72.0, 68.8; anal. calcd
for C27H28O4: C, 77.86; H, 6.78; O, 15.37; found C,
77.68; H, 6.63; FAB-MS m=z [MÀH]þ calcd 415.1909,
found 415.1897.
3.3. 3,4,5-Tri-O-benzyl-1,2-dideoxy-6-O-vinyl-D-xylo-
hept-1-ene (8)
Ethylvinyl ether (40 mL) and CH2Cl2 (5 mL) were
combined in a flame dried round-bottom flask. To
this mixture was added 1,10-phenanthroline (0.052 g,
29 mmol) followed by Pd(OAc)2 (0.065 g, 0.29 mmol),
which was allowed to stir for 15 min. To this mixture
was added 7 (0.81 g, 1.94 mmol) in CH2Cl2 (5 mL). The
flask was fitted with a condenser and refluxed for 3 days.
The solvent was removed under reduced pressure and
the dark oily residue was purified by column chroma-
tography using 4:1 hexanes–EtOAc as eluent to give 8
3.5. 1,2-Anhydro-b-D-idoseptanose (10)
Oxepine 9 (0.015 g, 0.036 mmol) was dried via azeotro-
pic distillation from toluene (3 ꢀ 5 mL) under reduced
pressure and dissolved in dry CH2Cl2 (2 mL). The
solution was cooled in an ice bath to 0 °C and a DMDO
(0.235 mL, 0.2 M) solution was added dropwise. The
mixture was stirred at 0 °C for 30 min and the solvent
was removed under reduced pressure. NMR showed
1
(0.775 g, 90%) as a clear colorless oil. ½aŠ þ8.4 (c 2.65,
quantitative conversion. H NMR (CDCl3) d 7.44–7.32
D
CHCl3); IR (KBr) cmÀ1 3063.37, 3029.62, 2871.49,
1616.06, 1496.49, 1454.06, 1321.00, 1200.47, 1087.66,
734.75, 697.14; 1H NMR (CDCl3) d 7.41–7.33 (m, 15 H),
6.46 (dd, 1 H, J 14.3, 6.8 Hz), 5.90 (ddd, 1 H, J 16.9,
10.9, 7.7 Hz), 5.35 (s, 1 H), 5.31 (d, 1 H, J 7.4 Hz), 4.84
(dd, 1 H, J 11.2, 11.2 Hz), 4.75 (dd, 2 H, J 11.5, 3.6 Hz),
4.68 (d, 1 H, J 11.7 Hz), 4.61 (d, 1 H, J 11.7 Hz), 4.45 (d,
1 H, J 11.7 Hz), 4.19 (dd, 1 H, J 6.6, 6.6 Hz), 4.12 (dd, 1
(m, 15 H), 4.88 (d, 1 H, J 11.2 Hz), 4.85 (d, 1 H,
J
13.2 Hz), 4.80 (d, 1 H, J 2.2 Hz), 4.75 (d,
1 H, J 11.5 Hz), 4.69 (d, 1 H, J 9.8 Hz), 4.60 (d, 1 H,
J 11.5 Hz), 3.85 (dd, 1 H, J 13.1, 3.5 Hz), 3.77 (m, 2 H),
3.67 (dd, 1 H, J 13.1, 6.6 Hz), 3.56 (m, 1 H), 2.99 (s, 1
H); 13C NMR (CDCl3) d 138.6, 138.1, 128.7, 128.6,
128.3, 128.1, 127.9 (2), 82.3, 80.6, 79.8, 78.3, 75.4, 73.6,
73.0, 64.1, 58.4.

1168
M. W. Peczuh et al. / Carbohydrate Research 339 (2004) 1163–1171
3.6. Methyl 3,4,5-tri-O-benzyl-
[method A]
D
-idoseptanoside––
residue was purified by column chromatography (4:1
hexanes–EtOAc) to give the a anomer (11) (0.038 g,
89%).
DMDO epoxidation of 9 (0.046 g, 0.11 mmol) in CH2Cl2
(2 mL) at 0 °C over 30 min was followed by solvent
removal under reduced pressure. To this residue was
added CH3OH (3 mL) and it was stirred overnight
(18 h). The solvent was removed under reduced pressure
and the residue was purified by column chromatogra-
phy, using 4:1 hexanes–EtOAc as eluent to give two
products.
3.10. Methyl 2,3,4,5-tetra-O-acetyl-a-D-idoseptanoside
(13)
Methyl septanoside 11 (0.034 g, 0.073 mmol) was dis-
solved in CH3OH (15 mL) and 10% Pd/C (10 mg) was
added. The solution was stirred under an atmosphere of
H2 for 4 h. The solution was filtered through a short pad
of Celite and washed with additional CH3OH (15 mL).
The solvent was removed under reduced pressure and
the resulting solid was dissolved in dry pyridine (2 mL)
to which Ac2O (0.5 mL) was added. The mixture was
stirred overnight (18 h) and quenched with water. The
solvent was removed under reduced pressure and the
residue was dissolved in CH2Cl2 (20 mL) and washed
with water (2 ꢀ 20 mL). The organic layer was dried
(Na2SO4) and the solvent removed under reduced
pressure. The resulting solid was purified by column
chromatography using 2:1 hexanes–EtOAc as eluent to
give 13 (0.024 g, 80%, two steps) as a white solid. Mp
3.7. Methyl 3,4,5-tri-O-benzyl-a-D-idoseptanoside (11)
The first fraction gave 11 (0.024 g, 48%) as a white solid.
Rf 0.33 (4:1 hexanes–EtOAc); Mp 88–90 °C; ½aŠ þ13.8
D
(c 1.70, CHCl3); IR (KBr) cmÀ1 3347.82, 3029.62,
2897.52, 1453.10, 1070.30, 750.17, 733.78, 695.21; 1H
NMR (CDCl3) d 7.34–7.29 (m, 15 H), 5.01 (d, 1 H, J
10.8 Hz), 4.92 (d, 1 H, J 10.8 Hz), 4.88 (d, 1 H,
J 10.8 Hz), 4.72 (d, 1 H, J 11.3 Hz), 4.65 (d, 1 H, J
10.6 Hz), 4.62 (d, 1 H, J 10.5 Hz), 4.39 (d, 1 H, J 6.2 Hz),
3.69–3.54 (m, 6H), 3.42 (s, 3 H), 3.03 (s, 1 H); 13C NMR
(CDCl3) d 138.8, 138.3, 137.9, 130.0, 128.9, 128.7, 128.6,
128.3, 128.2, 128.1(2), 128.0, 127.8, 104.4, 87.6, 80.4,
79.6, 76.7, 76.4, 73.9, 72.8, 59.6, 55.5; anal. calcd for
C28H32O6: C, 72.39; H, 6.94; O, 20.66; found C, 72.15;
H, 6.66; FAB-MS m=z [MÀH]þ calcd 463.2120, found
463.2113.
126–128 °C; ½aŠ þ79.8 (c 1.53, CHCl3); IR (KBr) cmÀ1
D
2924.52, 2852.20, 1752.98, 1378.85, 1222.65, 1125.26,
1
1071.26, 1049.09; H NMR (CDCl3) d 5.34–5.20 (m, 3
H), 5.06 (m, 1 H), 4.55 (d, 1 H, J 6.5 Hz), 3.83 (dd, 1 H,
J 12.5, 10.9 Hz), 3.61 (dd, 1 H, J 12.8, 4.4 Hz), 3.3 (s, 3
H), 2.05 (s, 3 H), 2.02 (s, 3 H), 2.00 (s, 6H); 13C NMR
(CDCl3) d 169.9, 169.6, 169.4, 169.0, 102.0, 73.9, 71.3,
71.2, 68.1, 59.5, 55.9, 20.9, 20.8, 20.6; anal. calcd for
C15H22O10: C, 49.72; H, 6.12; O, 44.16; found C, 49.82;
H, 6.47; FAB-MS m=z [MÀH]þ calcd 415.1909, found
415.1897.
3.8. Methyl 3,4,5-tri-O-benzyl-b-D-idoseptanoside (12)
The second fraction gave 12 (6 mg, 12%) as a clear
colorless oil. Rf 0.21 (4:1 hexanes–EtOAc); ½aŠ À49.2 (c
D
1
0.35, CHCl3); H NMR (CDCl3) d 7.35–7.28 (m, 15 H),
5.29 (s, 1 H), 4.85 (d, 1 H, J 9.4 Hz), 4.83 (s, 1 H), 4.70
(d, 1 H, J 11.9 Hz), 4.59–4.55 (m, 4 H), 4.01 (dd, 1 H, J
9.1, 6.2 Hz), 3.97 (d, 1 H, J 11.8 Hz), 3.94 (d, 1 H, J
12.3 Hz) 3.80 (dd, 1 H, J 6.1, 3.7 Hz) 3.76–3.71 (m, 2 H),
3.66 (m, 1 H), 3.46 (s, 3 H); 13C NMR (CDCl3) d 138.2,
128.7(2), 128.1(2), 128.0, 100.7, 85.2, 80.5, 77.8, 75.0,
73.2, 71.3, 71.2, 58.8, 56.0; FAB-MS m=z [MÀH]þ calcd
463.2120, found 463.2103.
3.11. 1,2:3,4-Di-O-isopropylidene-6-O-(3,4,5-tri-O-
benzyl-
D
-idoseptanosyl)-a-D-galactopyranose
Compound 9 (0.053 g, 0.127 mmol) was dried via azeo-
tropic distillation from toluene (3 ꢀ 10 mL) under
reduced pressure, dissolved in dry CH2Cl2 (2 mL), and
treated to DMDO (0.444 mL, 0.43 M) at 0 °C for 30 min.
The solvent was removed under reduced pressure to
afford 10. It was dissolved in dry THF (0.5 mL) and
cooled to À78 °C. To this solution was added 1,2;3,4-di-
3.9. Methyl 3,4,5-tri-O-benzyl-2-D-idoseptanoside––
[method B]
O-isopropylidene-a-D-galactopyranose (0.050 g, 0.191
mmol) in THF (1 mL), which had previously been az-
eotroped with toluene (3 ꢀ 10 mL). To this mixture was
added ZnCl2 (0.191 mL, 1.0 M in Et2O) and the mixture
was allowed to warm to rt overnight. Saturated
NaHCO3 (5 mL) was added and the mixture was
extracted with EtOAc (3 ꢀ 10 mL). The combined
organic fractions were dried (Na2SO4) and the solvent
was removed under reduced pressure. The residue was
purified by column chromatography, using 3:1 hexanes–
EtOAc as eluent to give two fractions.
DMDO epoxidation of 9 (0.039 g, 0.09 mmol) in CH2Cl2
(2 mL) at 0 °C over 30 min was followed by solvent re-
moval under reduced pressure. To the residue was added
NaOCH3 (0.006 g) in CH3OH (3 mL) and it was stirred
overnight (18 h). The reaction was quenched with water
(2 mL) and the solvent was removed under reduced
pressure. The residue was dissolved in CH2Cl2 (15 mL)
and washed with water (2 ꢀ 15 mL), dried (Na2SO4) and
the solvent was removed under reduced pressure. The

M. W. Peczuh et al. / Carbohydrate Research 339 (2004) 1163–1171
1169
3.12. 1,2:3,4-Di-O-isopropylidene-6-O-(3,4,5-tri-O-benz-
yl-a- -idoseptanosyl)-a- -galactopyranose (15)
3.49 (m, 6H), 3.00 (s, 1 H), 1.22 (d, 3 H, J 6.3 Hz), 1.20
(d, 3 H, J 6.1 Hz); 13C NMR (CDCl3) d 138.9, 138.3,
138.0, 128.9, 128.7, 128.6, 128.3, 128.1, 128.0, 127.9,
127.8, 101.2, 87.6, 80.5, 79.8, 76.7, 76.4, 73.9, 73.1, 69.4,
59.5, 23.6, 21.8; anal. calcd for C30H36O6: C, 73.15; H,
7.37; O, 19.49; found C, 72.76; H, 7.71; FAB-MS m=z
[MÀH]þ calcd 491.2434, found 491.2451.
D
D
The first fraction gave 15 (0.027 g, 30%) as a white foam.
Rf 0.27 (3:1 hexanes–EtOAc); ½aŠ À5.98 (c 0.94,
D
CHCl3); IR (KBr) cmÀ1 3527.17, 2986.23, 2905.24,
1455.03, 1382.71, 1069.33, 735.71, 698.11; 1H NMR
(CDCl3) d 7.32–7.30 (m, 15 H), 5.53 (d, 1 H, J 5.0 Hz),
4.97 (d, 1 H, J 10.8 Hz), 4.90 (d, 1 H, J 10.8 Hz), 4.85 (d,
1 H, J 10.8 Hz), 4.70 (d, 1 H, J 11.4 Hz), 4.63 (d, 1 H, J
11.5 Hz), 4.60 (dd, 1 H, J 8.0, 2.3 Hz), 4.52 (d, 1 H, J
6.4 Hz), 4.30 (dd, 1 H, J 7.1, 2.3 Hz), 4.28 (m, 1 H), 4.01
(dd, 1 H, J 6.3, 6.3 Hz), 3.80–3.76 (m, 2 H), 3.69–3.64
(m, 3 H), 3.57–3.52 (m, 3 H), 1.53 (s, 3 H), 1.44 (s, 3 H),
1.33 (s, 6H); 13C NMR (CDCl3) d 139.0, 138.4, 138.1,
128.8, 128.7, 128.6, 128.2(2), 128.1, 128.0(2), 127.8,
109.5, 108.9, 103.9, 96.6, 87.4, 80.4, 79.8, 76.6, 76.3,
73.8, 73.0, 71.2, 70.9, 67.2, 66.8, 59.9, 26.3, 26.2, 25.2,
24.7; FAB-MS m=z [MÀH]þ calcd 691.3121, found
691.3118.
3.15. Ethyl 3,4,5-tri-O-benzyl-1-thio-a-D-idoseptanoside
(18)
1,2-Anhydroseptanose 10 was prepared from 9 (0.031 g,
0.074 mmol) as described above. Compound 10 was
dissolved in dry CH2Cl2 (0.8 mL) and ethanethiol
(0.2 mL) and cooled to À78 °C. To this solution was
added trifluoroacetic anhydride (4 lL
) in C2HCl2
(0.196 mL). The mixture was stirred at À78 °C for 1 h,
then quenched by with satd NaHCO3 (5 mL). Addi-
tional CH2Cl2 (10 mL) was added and the organic layer
was washed with water (10 mL). The organic layer was
dried (Na2SO4) and solvent removed under reduced
pressure. Purification of the residue by column chro-
matography using 3:1 hexanes–EtOAc as eluent gave 18
3.13. 1,2:3,4-Di-O-isopropylidene-6-O-(3,4,5-tri-O-
-idoseptanosyl)-a-D-galactopyranose (16)
benzyl-b-
D
(0.012 g, 32%) as an off-white solid. Mp 64–66 °C; ½aŠ
D
The second fraction gave 16 (0.013 g, 15%), as a white
þ38.8 (c 1.00, CHCl3); IR (KBr) cmÀ1 3508.85, 3062.41,
foam. Rf 0.18 (3:1 hexanes–EtOAc); ½aŠ À100.54 (c
3030.59, 2870.52, 1496.49, 1454.06, 1069.33, 735.71,
1
D
0.68, CHCl3); 1H NMR (CDCl3) d 7.34–7.28 (m, 15 H),
5.53 (d, 1 H, J 5.0 Hz), 4.96 (s, 1 H), 4.76 (d, 1 H, J
11.2 Hz), 4.68 (d, 1 H, J 12.0 Hz), 4.65 (d, 1 H, J
12.1 Hz), 4.61–4.55 (m, 4 H), 4.30 (dd, 1 H, J 5.0,
2.3 Hz), 4.23 (dd, 1 H, J 8.0, 1.7 Hz), 4.05–3.98 (m, 4 H),
3.90 (m, 1 H), 3.78–3.67 (m, 4 H), 1.54 (s, 3 H), 1.43 (s, 3
H), 1.32 (s, 3 H), 1.29 (s, 3 H); 13C NMR (CDCl3) d
138.5, 138.4(2), 128.8, 128.7, 128.6(2), 128.1, 128.0,
127.9(2), 109.4, 108.8, 100.4, 96.5, 85.0, 80.6, 78.2, 74.6,
73.3, 71.6, 71.4, 71.3, 70.9, 70.8, 67.5, 67.2, 65.6, 59.8,
26.3, 26.2, 25.2, 24.6; FAB-MS m=z [MÀH]þ calcd
691.3121, found 691.3118.
698.11; H NMR (CDCl3) d 7.34–7.26 (m, 15 H), 5.00
(d, 1 H, J 10.8 Hz), 4.85 (d, 2 H, J 10.7 Hz), 4.71 (d, 1 H,
J 11.4 Hz), 4.64 (d, 1 H, J 11.2 Hz), 4.62 (d, 1 H,
J 10.9 Hz), 3.82 (dd, 1 H, J 12.2, 10.6 Hz), 3.76–3.73 (m,
1 H), 3.67 (d, 1 H, J 9.0 Hz), 3.59–3.54 (m, 3 H), 3.09 (s,
1 H), 2.75–2.56 (m, 2 H), 1.30 (t, 3 H, J 7.4 Hz); 13C
NMR (CDCl3) d 138.8, 138.3, 137.9, 128.9, 128.7, 128.6,
128.3, 128.2, 128.1, 128.0, 127.9, 87.9, 87.1, 81.7, 80.3,
76.7, 76.3, 73.8, 73.4, 61.1, 24.8, 15.3; FAB-MS m=z
[MþH]þ calcd 495.2221, found 495.2205.
3.16. Allyl 3,4,5-tri-O-benzyl-a-D-idoseptanoside (19)
3.14. Isopropyl 3,4,5-tri-O-benzyl-a-
(17)
D
-idoseptanoside
DMDO epoxidation of 9 (0.038 g, 0.0091 mmol) in
CH2Cl2 (2 mL) at 0 °C over 30 min was followed by
solvent removal under reduced pressure. The subsequent
addition was done in a similar fashion to those described
for glucals.18 10 was dissolved in dry THF (1 mL) and
cooled on an ice bath to À10 °C. Allylmagnesium bro-
mide (0.032 mL, 1.0 M) was added dropwise and the
mixture was stirred for 30 min at À10 °C. The reaction
was quenched with saturated NH4Cl (5 mL) solution.
EtOAc (10 mL) was added and the reaction placed in a
separatory funnel. The EtOAc was separated, and the
aqueous layer was extracted with additional EtOAc
(10 mL). The combined organic fractions were washed
with water (20 mL), dried (Na2SO4) and the solvent
removed under reduced pressure. The residue was
purified by column chromatography using 3:1 hexanes–
EtOAc as eluent to give 19 (0.015 g, 33%) as a waxy
DMDO epoxidation of 9 (0.028 g, 0.067 mmol) in
CH2Cl2 (2 mL) at 0 °C over 30 min was followed by
solvent removal. To this residue was added anhydrous
2-propanol (3 mL) and it was stirred overnight (18 h).
The solvent was removed under reduced pressure and
the residue was purified by column chromatography,
using 4:1 hexanes–EtOAc as eluent to give 17 (0.023 g,
69%) as a white solid. Mp 79–81 °C; ½aŠ þ20.6 (c 1.95,
D
CHCl3); IR (KBr) cmÀ1 3546.45, 3029.62, 2968.87,
2905.24, 1454.06, 1042.34, 735.71, 695.21; 1H NMR
(CDCl3) d 7.31–7.28 (m, 15 H), 4.99 (d, 1 H, J 10.7 Hz),
4.91 (d, 1 H, J 10.8 Hz), 4.87 (d, 1 H, J 10.8 Hz), 4.72 (d,
1 H, J 11.3 Hz), 4.64 (d, 1 H, J 11.9 Hz), 4.61 (d, 1 H,
J 11.2 Hz), 4.57 (d, 1 H, J 5.8 Hz), 3.93 (m, 1 H), 3.71–

1170
M. W. Peczuh et al. / Carbohydrate Research 339 (2004) 1163–1171
solid. ½aŠ À33.0 (c 0.61, CHCl3); IR (KBr) cmÀ1
The reaction mixture was extracted with EtOAc
(2 ꢀ 10 mL) and dried (Na2SO4). The residue was puri-
fied by column chromatography, using 4:1 hexanes–
EtOAc as eluent to give 21 (0.028 g, 73%) as a clear,
D
3552.24, 3028.66, 2904.27, 1453.10, 1122.37, 1076.08,
740.53, 696.18; 1H NMR (CDCl3) d 7.33–7.26 (m, 15 H),
5.90 (m, 1 H), 5.13–5.03 (m, 2 H), 4.89 (d, 1 H,
J 11.0 Hz), 4.76 (d, 1 H, J 10.9 Hz), 4.67 (d, 1 H, J
11.6 Hz), 4.63 (d, 1 H, J 11.7 Hz), 4.56 (d, 1 H,
J 11.1 Hz), 4.03 (dd, 1 H, J 13.7, 3.9 Hz), 3.79 (dd, 1 H,
J 8.9, 7.1 Hz), 3.65–3.42 (m, 1 H), 3.56 (d, 1 H, J
5.5 Hz), 3.55 (d, 1 H, J 3.5 Hz), 3.52 (d, 1 H, J 4.0 Hz),
3.46 (dd, 1 H, J 9.0, 9.0 Hz), 3.29 (td, 1 H, J 8.7, 2.9 Hz),
slightly yellow syrup. ½aŠ þ17.8 (c 1.15, CHCl3); IR
D
(KBr) cmÀ1 3450.03, 3029.62, 2889.81, 1454.06, 1071.26,
736.67, 697.14; 1H NMR (CDCl3) d 7.52 (d, 2 H, J
6.8 Hz), 7.34–7.28 (m, 18H), 5.11 (d, 1 H, J 7.8 Hz), 5.00
(d, 1 H, J 10.8 Hz), 4.91 (d, 1 H, J 10.8 Hz), 4.87 (d, 1 H,
J 10.8 Hz), 4.71 (d, 1 H, J 11.3 Hz), 4.65 (d, 1 H, J
9.5 Hz), 4.63 (d, 1 H, J 10.7 Hz), 3.91 (dd, 1 H, J 12.1,
10.7 Hz), 3.78–3.59 (m, 5 H), 3.17 (s, 1 H); 13C NMR
(CDCl3) d 138.7, 138.2, 137.8, 134.2, 132.3, 129.3, 129.1,
128.9, 128.7, 128.6, 128.4, 128.3, 128.1, 128.0, 127.9,
127.7, 91.1, 87.1, 81.4, 80.2, 76.7, 76.3, 73.8, 72.9, 61.2;
anal. calcd for C33H34O5S: C, 73.04; H, 6.31; O, 14.74; S,
5.91; found C, 72.74; H, 6.29; S, 5.70.
2.93 (s, 1 H), 2.58–2.54 (m, 1 H), 2.31–2.28 (m, 1 H); 13
C
NMR (CDCl3) d 138.8, 138.4, 138.2, 135.2, 128.9,
128.6(2), 128.3, 128.2, 128.1, 128.0, 127.9, 127.8, 117.1,
84.8, 83.5, 82.9, 81.6, 76.3, 75.7, 74.4, 72.5, 68.6, 37.6;
FAB-MS m=z [MþH]þ calcd 475.2485, found 475.2487.
3.17. 3,4,5-Tri-O-benzyl-a-D-idoseptanosyl azide (20)
This procedure is based on one described.18 DMDO
epoxidation of 9 (0.032 g, 0.077 mmol) in CH2Cl2 (2 mL)
at 0 °C over 30 min was followed by solvent removal
under reduced pressure. The residue was dissolved in
DMF (1 mL) and NaN3 (0.075 g, 1.54 mmol) in water
(0.5 mL) was added. After 4 h, water (5 mL) was added
to the solution and it was extracted with EtOAc
(2 ꢀ 15 mL). The organic layers were dried (Na2SO4)
and solvent was removed under reduced pressure. The
material was purified by column chromatography,
using 4:1 hexanes–EtOAc as eluent to give 20 (0.025 g,
4. Supplementary Material
Complete crystallographic data for the structural anal-
ysis of 9 have been deposited in the Cambridge Crys-
tallographic Data Centre (CCDC), No 223661. Copies
of this information may be obtained free of charge from:
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(Fax: +44-1223-336033; web: www.ccdc.cam.ac.uk/
conts/retrieving.html; email: deposit@ccdc.cam.ac.uk).
69%) as a white waxy solid. Mp 62–64 °C; ½aŠ þ74.5 (c
D
1.85, CHCl3); IR (KBr) cmÀ1 3367.10, 3030.59,
2899.45, 2107.81, 1454.06, 1235.18, 1068.37, 749.21,
695.21; H NMR (CDCl3) d 7.35–7.26 (m, 15 H), 5.01
Acknowledgements
1
The authors thank Chris Incarvito (Yale University) for
collection of the X-ray data, Martha Morton (Univer-
sity of Connecticut) for help with collection and inter-
pretation of NMR data, John D. Stevens for kindly
(d, 1 H, J 10.8 Hz), 4.93 (d, 1 H, J 6.1 Hz), 4.91 (d, 1 H,
J 12.5 Hz), 4.87 (d, 1 H, J 12.4 Hz), 4.72 (d, 1 H, J
11.3 Hz), 4.65 (d, 1 H, J 10.7 Hz), 4.62 (d, 1 H, J
10.5 Hz), 3.75–3.69 (m, 4 H), 3.59–3.55 (m, 3 H), 3.07 (s,
1 H); 13C NMR (CDCl3) d 138.6, 138.0, 137.6, 128.9,
128.7, 128.6, 128.4, 128.2(2), 128.1, 127.9(2), 93.3, 86.9,
80.1, 79.7, 76.7, 76.3, 73.9, 72.5, 62.1; anal. calcd for
C27H29N3O5: C, 68.19; H, 6.15; N, 8.84; O, 16.82; found
C, 68.27; H, 5.93; N, 8.80.
supplying a sample of methyl a-L-idoseptanoside, and
Nabyl Merbouh for a critical reading of the manuscript.
Steve Castro and Sara Rosemeier helped in the prepa-
ration of 9. This work was supported by the University
of Connecticut and the University of Connecticut
Research Foundation.
3.18. Phenyl 3,4,5-tri-O-benzyl-1-thio-a-D-idoseptanoside
(21)
References
DMDO epoxidation of 9 (0.030 g, 0.07 mmol) in CH2Cl2
(2 mL) 0 °C over 30 min was followed by solvent
removal under reduced pressure. The remainder of this
procedure is based on one described.18 In a separate
flame-dried flask, thiophenol (0.073 mL, 0.72 mmol) was
dissolved in dry THF (1 mL) and put on a 0 °C ice bath.
n-Butyllithium (0.446 mL, 1.6 M) was added to this
solution dropwise and stirred for 5 min. To this solution
was added 10 in dry THF (1 mL). The mixture was
stirred at 0 °C for 30 min, and water (10 mL) was added.
1. Yasumoto, T.; Murata, M. Chem. Rev. 1993, 93, 1897–
1909.
2. (a) Eschenmoser, A. Science 1999, 284, 2118–2124; (b)
Gellman, S. H. Acc. Chem. Res. 1998, 31, 173–180; (c)
Porter, E. A.; Wang, X.; Lee, H. S.; Weisblum, B.;
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