Construction of a branched chain at C-3 of a hexopyranoside. Synthesis of miharamycin sugar moiety analogs

Article abstract of DOI:10.1016/S0008-6215(99)00307-9

Synthesis of the conveniently protected epimer at C-3' of the miharamycin sugar moiety was accomplished starting from the corresponding 3,3'-spiroepoxide. Reaction of the epoxide with lithium cyanide, followed by hydrolysis and spontaneous cyclization, af

Full text of DOI:10.1016/S0008-6215(99)00307-9

www.elsevier.nl/locate/carres
Carbohydrate Research 325 (2000) 1–15
Construction of a branched chain at C-3 of a
hexopyranoside. Synthesis of miharamycin sugar moiety
analogs
Ame´lia Rauter a,*, Maria Ferreira a, C. Borges a, Teresa Duarte b, Fa´tima Piedade b,
Maria Silva b, Helena Santos c
a Departamento de Qu´ımica e Bioqu´ımica, Faculdade de Cieˆncias, Uni6ersidade de Lisboa, Edif´ıcio C1, 5° Piso,
Campo Grande, P-1700 Lisbon, Portugal
b Centro de Qu´ımica Estrutural, IST, P-1096 Lisbon, Portugal
c Instituto de Tecnologia Qu´ımica e Biolo´gica, P-2780 Oeiras, Portugal
Received 9 November 1998; revised 7 February 1999; accepted 17 November 1999
Dedicated to the memory of Professor Stanislas Czernecki
Abstract
Synthesis of the conveniently protected epimer at C-3% of the miharamycin sugar moiety was accomplished starting
from the corresponding 3,3%-spiroepoxide. Reaction of the epoxide with lithium cyanide, followed by hydrolysis and
spontaneous cyclization, afforded the intermediate deoxylactone methyl 4,6-O-benzylidene-3-C-(carboxymethyl)-a-D-
glucopyranoside-3%,2-lactone (8). Stereoselective hydroxylation with MoO5·py·HMPA, reduction with lithium alu-
minum hydride and cyclization with diethyl azodicarboxylate–triphenylphosphine gave the target molecule methyl
2,3¦-anhydro-4,6-O-benzylidene-3-C-[(R)-1,2-dihydroxyethyl]-a- -glucopyranoside (5). Direct reduction of 8 gave
D
other analogs having no C-3% hydroxyl group together with having a C-3¦ hydroxyl group (hemiacetal). In addition,
C-3% epimers were also synthesized through C-3%, C-3¦ dihydroxy analogs. Wittig reaction of an appropriate
ketosugar with [(ethoxycarbonyl)methylene]triphenylphosphorane leading to a 7:3 Z/E mixture, followed by hydroxy-
lation with osmium tetroxide, reduction and cyclization afforded the target molecule 5 and the miharamycin sugar
moiety methyl 2,3¦-anhydro-4,6-O-benzylidene-3-C-[(S)-1,2-dihydroxyethyl]-a-D-glucopyranoside. Examination of
X-ray data for 5 and its NMR spectroscopy data allowed us to explain a contradiction reported in the literature.
© 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Miharamycin sugar moiety analogues; Stereoselective synthesis; Branched-chain sugars
1. Introduction
to cause the rice blast disease [1]. In a previous
work, we have described the synthesis of the
amipurimycin sugar moiety [2]. Miharamycin
A (1) and B (2) are produced by Streptomyces
miharaensis SF-489 [1] and the structural stud-
ies of these two antibiotics were reported
Amipurimycin and miharamycin A (1) and
B (2) are nucleoside antibiotics that act as
potent inhibitors of Pyricularia oryzae, known
1
based on H and 13C NMR spectral analysis
* Corresponding author. Fax: +351-21-750-0088.
E-mail address: aprauter@mail.telepac.pt (A. Rauter)
[3].
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(99)00307-9

2
A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
cyanide in anhydrous tetrahydrofuran for 12 h
under reflux and argon atmosphere, followed
by removal of the benzoyl group, afforded the
nitrile 7 isolated by column chromatography
with silica gel in 78% yield. Compound 7 is
very unstable and hydrolyses spontaneously in
the presence of traces of silica gel, leading to
the formation of the lactone 8 in 82% yield.
Attempts to hydrolyse 7 under mild acidic
conditions such as ammonium chloride in
methanol under reflux for 24 h left the starting
material unchanged. When sodium cyanide in
dimethylformamide or potassium cyanide in
methanol were used under reflux, followed by
addition of ammonium chloride, a complex
mixture of products was obtained, also con-
taining traces of the lactone 8 as detected by
thin-layer chromatography (TLC).
Hydrolysis and esterification of 7 was tried
by treatment with sodium methoxide in
methanol at room temperature for 1 week and
no reaction occurred. Alkylation of 7 to an
N-alkylnitrilium ion with the system 2-chloro-
propane–FeCl3, followed by addition of tri-
ethylsilane and hydrolysis [6], did not give the
expected aldehyde, but led to the complete
decomposition of the substrate. All these at-
tempts made it clear that the described condi-
tions for the formation of 8 are so far the
most suitable ones.
Further modifications of 8 were performed
to provide analogues of the hexopyranosidic
sugar moiety of miharamycin in order to al-
low structure–activity relationship studies.
Reduction of the lactone 8 with diisobutylalu-
minum hydride [7] in toluene at −40 °C for
1 h gave the lactols 9a,b in 34% yield and ratio
2:1, together with the primary alcohol 10 in
52% yield. Treatment of 9 with boron tri-
fluoride diethyl etherate–triethylsilane [8] in
acetonitrile at −30 °C afforded 11 (36%
yield). The opening of the 4,6-O-benzylidene
residue was highly regioselective, and this re-
sult is in good agreement with a previous
observation given by Garegg et al. [9] for the
reductive opening of benzylidene dioxane
rings using electrophiles with a small steric
requirement. The low yield for the cyclic ether
11 from the lactone 8 resulting from this
pathway encouraged us to examine the reduc-
tion of 8 with lithium aluminum hydride in
tetrahydrofuran. In this case, 10 was obtained
Synthesis of the hexopyranosidic carbohydrate
moiety 3 has been described in the literature
by Sinay¨ and Fairbanks [4] by stereoselective
reduction with NaBH4 of the ketosugar 4. In
this work, we report a highly stereoselective
branched-chain construction at C-3 of a hexo-
pyranosidic unit 5, which is an epimeric
analog of the miharamycin sugar moiety 3
and may be considered as a precursor for its
synthesis as depicted in Scheme 1, as well as
other analogues containing the tetrahydro-
furan ring or this ring hydroxylated at C-3¦.
2. Results and discussion
The new highly stereoselective synthesis of 5
was accomplished using as starting material
the epoxide 6 [5] (Scheme 2), which possesses
the appropriate configuration at C-3. Spectro-
scopic data of 6 were in agreement with those
reported for it by Yoshimura et al. [5], with
the exception of the chemical shifts given for
H-1 and H-2 by those authors, values of
which should be interchanged as confirmed by
1
us by H–13C heteronuclear multiple quantum
correlation. Reaction of 6 with lithium
Scheme 1.

A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
3
Scheme 2. (a) LiCN 0.5 M in DMF, THF, D, 12 h (78%); (b) H2O, silica gel (82%); (c) DIBAHL, toluene–THF, 3 h, −78 °C
and 1 h, −40 °C; (d) LiAlH4, THF, 5 h, 40 °C and 1 h, D; (e) BF3·Et2O, Et3SiH, CH3CN, −30 °C, 1.5 h (36%); (f) Ph3PꢀDEAD,
,
CHCl3, 4 A powdered molecular sieves, 2.5 h, 5 °C (82%) for 12 and Ac2O, DMAP, py, room temperature, 3 h (94%) for 13.
in 82% yield. Cyclization with diethyl azodicar-
boxylate–triphenylphosphine [10,11] allowed
the preparation of 12 in 82% yield. Since, H-
3¦a, H-3¦b, H-3%a and H-3%b of 12 consist of an
ABCD spin system and the AB part is over-
lapped with H-6e, we have synthesized its 3-
O-acetyl derivative 13 by reaction with ace-
tic anhydride, 4-dimethylaminopyridine and
pyridine at room temperature for 3 h in 94%
yield. This derivative presents the H-3¦a (A),
H-3¦b (B), H-3%a (C) and H-3%b (D) protons
each as a multiplet at l 4.21, 4.04, 2.53 and
2.20, respectively. The coupling constants
Hydroxylation of 8 (Scheme 3) was accom-
plished using lithium diisopropylamide in te-
trahydrofuran at −78 °C to obtain the
corresponding enolate, which then reacted with
the molybdenum pentoxide–pyridine–hexa-
methylphosphoramide complex (MoOs·py·
HMPA) [12–14] for 3 h at −78 °C affording
the 3%-hydroxylactone 14 in 50% yield, based
on the reacted starting material, which was re-
covered in 48% yield. Reduction of 14 with
lithium aluminum hydride in tetrahydrofuran,
followed by reaction with diethyl azodicar-
boxylate–triphenylphosphine in chloroform at
5 °C [10,11] led to the synthesis of the desired
cyclic ether 5 in 23% overall yield from 14.
The confirmation of the expected S configu-
ration of the new stereogenic center [15] in 14
J
AB= −7.33, JAC =9.74, JAD=1.88, JBC=
9.88, JBD=7.00 and JCD = −13.63 Hz were
determined by computational simulation using
the iterative program LAOCOON (Fig. 1).

4
A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
Fig. 1. (a) Experimental and (b) theoretical 1H NMR spectra of 13 (chemical shifts between l 4.32 and 2.02) analysed as an
1
ABCD spin system; (c) H NMR spectrum of 13 (chemical shifts between l 4.27 and 4.00); (d) simulated spectrum of the nucleus
1
AB; (e) H NMR spectrum of 13 (chemical shifts between l 2.62 and 2.10); (f) simulated spectrum of the nucleus CD.
one described by those authors, who used as
starting material the ketosugar 16 [17], and its
Wittig reaction with ethyl diethylphospho-
noacetate, followed by reduction with lithium
aluminum hydride, acetylation of the hydroxyl
groups formed, addition of osmium tetroxide,
deprotection and cyclization with camphorsul-
was effected by nuclear Overhauser effect
spectroscopy (NOESY) by detection of the
interaction between OH-3ꢀOH-3% and H-3%ꢀH-
5 (Fig. 2). Since the spectroscopic data of 5
were not in agreement with the corresponding
data reported by Hara et al. [16], we have
investigated a reaction pathway similar to the

A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
5
fonyl chloride–pyridine. The branched-chain
construction of the miharamycin hexopyr-
anosidic sugar moiety was accomplished by
a four-step sequence. Olefination of the ke-
tosugar 16 was performed with [(ethoxy-
carbonyl)methylene]triphenylphosphorane af-
fording a 7:3 mixture of the Z/E isomers 17
and 18, respectively, in 88% yield (Scheme 4).
Oxidation of the mixture 17/18 with osmium
tetroxide in pyridine [18] led to the synthesis
of a mixture of stereoisomers in quantitative
yield, whereas when osmium tetroxide was
used in catalytic amount in the presence of
4-methylmorpholine N-oxide in acetone–wa-
ter, [19] the mixture 19a,b was isolated in 66%
yield. Reduction of 19a,b with lithium alu-
minum hydride in tetrahydrofuran under
reflux for 24 h led to a 3:1 mixture of tetrols
20a,b in 48% yield and to secondary products,
i.e., the lactols 21a,b in a 1:1 ratio and 22,
obtained in 14 and 9% yield, respectively.
When the reaction was conducted at 25 °C for
Scheme 3. (a) LDA, THF, −78 °C, 50 min; MoO5·py·HMPA, −78 °C, 3 h (50%); (b) LiAlH4, THF, D, 96 h; DEADꢀPh3P,
,
CHCl3, 5 °C, 4 A powdered molecular sieves (23%).
Fig. 2. (a) NOESY spectrum of 14; (b) amplified spectrum of 14 between l 3.95 and 3.67.

6
A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
Scheme 4. (a) Ph3PꢁCHCO2Et, CHCl3, D, 5.5 h (88%); (b) OsO4, py., room temperature, 2.5 h (100%); (c) LiAlH4, THF, D,
,
24 h; (d) Ph3PꢀDEAD, CHCl3, 4 A powdered molecular sieves, 5 °C, 2.5 h.
boxylate–triphenylphosphine. Compound 3
3.5 h, 20a,b was isolated only in 36% yield but
the lactols 21a,b and 22 were obtained in 18
was compared with a sample kindly sent by
Professor P. Sinay¨ and exhibited spectroscopic
data which are in full agreement with those
reported for it by Sinay¨ and Fairbanks [4].
These authors have unambiguously elucidated
the structure of 3 by X-ray crystallography.
Since spectroscopic and physical data of com-
pound 5 were in complete accordance with the
data reported by Hara et al. [16] for ‘their’
compound 3, we assume that they had as-
signed an erroneous structure. Single-crystal
X-ray crystallographic analysis of 5 confirmed
the proposed structure and established the
C-3% configuration to be R (Fig. 3). The most
noticeable differences between our molecule
and the one reported by Sinay¨ and Fairbanks
1
and 27% yield, respectively. The H NMR
spectrum of 21a,b was identical to the one of
the lactols obtained by reduction of the lac-
tone 14. The configuration of C-3¦ in 22 was
1
inferred by the analysis of its H NMR spec-
trum since H-3¦ appears as a doublet coupling
only with OH-3¦ with J3¦,OH-3¦=7.59 Hz,
confirmed by addition of deuterium oxide.
The absence of coupling with H-3% is only
possible if both protons are trans to each
other. Cyclization of 20a,b with diethyl azodi-
carboxylate–triphenylphosphine in chloro-
form at 5 °C for 2.5 h [10,11] afforded the
isomers 5 and 3 in 52 and 16% yields, respec-
tively. Attempts to use diisopropyl azodicar-
boxylate–triphenylphosphine as cyclization
system did not improve the yields of 5 and 3
nor simplify their chromatographic purifica-
tion, since the starting material was also
present under the same experimental condi-
tions used with the system diethyl azodicar-
,
[4] are the C-phenyl distance, 1.506(11) A and
all the torsion angles around atoms C-3, C-
3%and C-3%%, particularly O-3%ꢀC-3%ꢀC-3ꢀO-3
whose value 38.7(8)°, compared with the cor-
responding angle of 160.67°, is determinant in
the assignment of the correct configuration
(see Tables 2 and 3).

A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
7
This synthetic pathway afforded complex
mixtures but allowed the inconsistencies re-
ported in the literature for the synthesis of the
miharamycin sugar moiety to be explained.
tor mass spectrometer equipped with an
inhomogeneous field, plane parallel electro-
static analyzer and a 2048 microchannel
photodiode (MCP) array detector and using
glycerol as matrix. Analytical TLC was per-
formed on E. Merck aluminum pre-coated
plates of Silica Gel 60 F254 (thickness of 0.2
mm) with detection by spraying with a 2.5%
vanillin–sulfuric acid soln. Column chro-
matography was performed using Silica Gel
60 G (0.040–0.063 mm, E. Merck) and elution
under reduced pressure. Evaporation of sol-
vents was carried out under reduced pressure
under 40 °C. Elemental analysis was con-
ducted at the Service of Microanalyses of
Instituto Superior Te´cnico da Universidade
Te´cnica de Lisboa.
3. Experimental
General methods.—Melting points were de-
termined with a melting point apparatus (Tot-
1
toli) and are uncorrected. H NMR spectra
were recorded in CDCl3 at 250, 300 and 500
MHz and 13C NMR spectra recorded in
CDCl3 at 62.9 MHz. Chemical shifts are ex-
pressed in ppm downfield from Me4Si.
NOESY spectra were recorded in CDCl3 at
1
500 MHz at 290 K. The H and 13C HMQC
spectra was recorded in CDCl3 at 125.77 MHz
(13C) and 500.13 MHz (1H). The simulation of
1H NMR spectra was performed using the
iterative spin simulation computer program
LAOCOON with a Varian Unity 300. HRMS
mass spectra were recorded with a Finnigan
FT/MS 2001-DT FTICR mass spectrometer
equipped with a 3 T superconducting magnet
and interfaced with a Spectra-Physics Quants-
Ray GCR-11 Nd:YAG laser operated at the
fundamental wavelength (1064 nm). Electron
impact mass spectra were obtained with a Jeol
JMS-DX300 (70 eV). The LSIMS mass spec-
tra were recorded with a VG-ZAB-T four-sec-
Methyl 2,3¦-anhydro-4,6-O-benzylidene-3-
C-[(S)-1,2-dihydroxyethyl]-h- -glucopyran-
D
oside (3).—Triphenylphosphine (210 mg, 0.81
,
mmol) and 4 A powdered molecular sieves (30
mg) were added to a soln of 20a,b (100 mg,
0.29 mmol) in dry CHCl3 (8 mL) at room
temperature (rt) under argon. After cooling to
5 °C, diethyl azodicarboxylate (DEAD) (0.15
mL, 0.95 mmol) was added and the reaction
mixture was stirred at 5 °C for 2.5 h. Filtra-
tion and evaporation gave a residue which
was purified by column chromatography with
2:1 EtOAc–toluene giving 3 as a solid (15 mg,
16%); mp 188–191 °C; [h]2D0+94.4° (c 0.93,
Fig. 3. Molecular drawing of diol 5 showing the crystallographic numbering scheme (ORTEP II, ellipsoids with 40% probability).

8
A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
Table 1
Method B. A soln of 14 (50 mg, 0.15 mmol)
in dry THF (0.5 mL) was added to a suspen-
sion of LiAlH4 (28 mg) in dry THF (3.5 mL)
at 0 °C under argon. After heating the reac-
tion mixture under reflux for 96 h, the workup
was the same as described for 20a,b. The
residue (44 mg) was dissolved in dry CHCl3
(2.5 mL) and triphenylphosphine (55 mg, 0.21
Crystal data and structure refinement for 5
Empirical formula
Formula weight
Temperature (K)
Wavelength (A)
Crystal system
Space group
C16H20O7
324.36
293(2)
0.71069
orthorhombic
P212121
,
Unit cell dimensions
,
mmol) and 4 A powdered molecular sieves (6
,
a (A)
5.433(8)
10.672(1)
26.903(4)
1559.7(7)
4
1.381
0.067
688
1.51–24.96
05h56; 05k512;
05l531
1626/1626
[Rint=0.0000]
mg) were added to the soln, under argon.
DEAD (0.05 mL, 0.3 mmol) was added to the
reaction mixture, previously cooled to 5 °C.
Stirring at 5 °C for 3 h, filtration and evapora-
tion afforded a mixture separated by prepara-
tive TLC with 1:1 EtOAc–toluene giving 5 (11
mg, 23% global yield): mp 124–126 °C
(CH2Cl2–cyclohexane); [h]2D0 +75.1° (c 1.1,
,
b (A)
,
c (A)
3
,
Volume (A )
Z
Dcalcd (Mg m−3
)
Absorption coefficient (mm−1
)
F(000)
q Range for data collection (°)
Index ranges
1
CHCl3); IR (KBr): w 3396 cm−1 (OH); H
Reflections collected/unique
NMR (500 MHz): l 7.56–7.50 (m, 2 H, Ph),
7.24–7.22 (m, 3 H, Ph), 5.57 (s, 1 H, CHPh),
4.93 (dt, 1 H, J3%,OH 3.21, J3%,3¦a 7.8 Hz, H-3%),
4.75 (d, 1 H, J1,2 5.05 Hz, H-1), 4.32 (dd, 1 H,
J6a,6e 10.08, J5,6e 4.6 Hz, H-6e), 4.29 (t, 1 H,
J3¦a,3¦b 7.8 Hz, H-3¦a), 4.11 (d, 1 H, H-2), 3.93
(d, 1 H, J4,5 10.08 Hz, H-4), 3.83 (dt, 1 H, J5,6a
10.08 Hz, H-5), 3.76 (t, 1 H, H-6a), 3.71 (t, 1
H, J3%,3¦b 7.8 Hz, H-3¦b), 3.40 (s, 3 H, OCH3);
13C NMR: l 137.1, 129.4, 128.5, 126.1 (Ph),
102.3 (CHPh), 99.7 (C-1), 83.3 (C-4), 82.3
(C-2), 76.3 (C-3), 72.6 (C-3¦), 71.6 (C-3%), 69.3
(C-6), 59.7 (C-5), 55.7 (OCH3); EIMS: m/z
292 (95, [M−CH3OH]+), 149 (23, [C6H5-
CHOCH2CHO]+), 105 (49, [C6H5CO]+), 107
(100, [C6H5CHOH]+); LSIMS: m/z 325 (100;
[M+H]+), 293 (92; [M+H−CH3OH]+),
107 (40; [C6H5CHOH]+); HRMS: calcd for
C16H20O7 324.348, found: 324.121; Crystal
data for 5, crystallized from CH2Cl2–cyclo-
hexane: data were collected in a CAD4 diffrac-
tometer using graphite monochromated Mo
Ka radiation. Details of data collection and
refinement are presented in Table 1. 1626
reflections were measured and used in the soln
and refinement of the crystal structure by
direct methods. Remaining non-hydrogen and
hydrogen atoms were located in successive
difference Fourier syntheses. The structure
was refined by least-squares methods until
convergence, allowing the refinement of
Flack’s parameter with all the other parame-
ters in the same full matrix. All calculations
required to solve and refine the molecular
Completeness to 2q=24.96 (%) 99.9
Refinement method
full-matrix least-squares
on F2
Data/restraints/parameters
Goodness-of-fit on F2
1626/0/288
1.210
Final R indices [I\2|(I)]
R1=0.0601,
wR2=0.0940
R1=0.1245
wR2=0.1252
0(5)
R indices (all data)
Absolute structure parameter
Largest difference peak and hole 0.233 and −0.196
−3
,
(e A
)
CHCl3); IR (KBr): w 3387 cm−1 (OH); H
NMR (300 MHz): l 7.60–7.43 (m, 5 H, Ph),
5.63 (s, 1 H, CHPh), 4.89 (d, 1 H, J1,2 5.43 Hz,
H-1), 4.44 (dd 1 H, J3%,3¦a 4.38, J3¦a,3¦b 9.48 Hz,
H-3¦a), 4.35 (dd, 1 H, J5,6e 4.59, J6a,6e 9.72 Hz,
H-6e), 4.27–4.17 (m, 2 H, H-3%, H-5), 4.08 (d,
1 H, H-2), 3.98 (d, 1 H, H-3¦b), 3.93 (d, 1 H,
J4,5 9.72 Hz, H-4), 3.66 (t, 1 H, H-6a), 3.54 (s,
1
13
3 H, OCH3), 2.63 (s, OH); C NMR: l 137.0,
129.4, 128.4, 126.5 (Ph), 103.0 (CHPh), 99.3
(C-1), 83.4, 82.0 (C-4, C-2), 78.6 (C-3¦), 77.5
(C-3), 77.0 (C-3%), 70.0 (C-6), 60.5 (C-5), 55.9
(OCH3); HRMS: calcd for C16H20O7 324.348,
found: 324.121.
Methyl 2,3¦-anhydro-4,6-O-benzylidene-3-
C-[(R)-1,2-dihydroxyethyl]-h-
oside (5)
D
-glucopyran-
Method A. The same procedure described
above for 3 was used, giving 5 as a solid (49.3
mg, 52%).

A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
9
Table 2
Table 2
,
Bond lengths (A) and angles (°) for 5
C-6ꢀC-5ꢀC-4
108.8(8)
119.1(10)
105.2(8)
118.2(9)
120.6(7)
121.2(9)
106.9(6)
121.4(10)
119.1(10)
121.0(11)
Bond lengths
C-14ꢀC-15ꢀC-16
O-1ꢀC-1
O-1ꢀC-10
O-3%ꢀC-3%
C-3%ꢀC-3
C-3%ꢀC-3¦
O-6ꢀC-4
O-6ꢀC-7
O-3ꢀC-3
C-1ꢀO-5
C-1ꢀC-2
C-4ꢀC-3
C-4ꢀC-5
C-3ꢀC-2
O-2ꢀC-2
O-2ꢀC-3¦
O-7ꢀC-7
O-7ꢀC-6
O-5ꢀC-5
C-7ꢀC-11
C-16ꢀC-11
C-16ꢀC-15
C-5ꢀC-6
C-15ꢀC-14
C-11ꢀC-12
C-12ꢀC-13
C-13ꢀC-14
1.398(8)
O-7ꢀC-6ꢀC-5
1.431(9)
1.413(8)
1.515(8)
1.534(9)
1.429(7)
1.430(8)
1.423(7)
1.398(9)
1.534(10)
1.497(9)
1.518(9)
1.551(8)
1.401(9)
1.433(10)
1.423(9)
1.457(13)
1.442(9)
1.506(11)
1.367(11)
1.382(12)
1.509(11)
1.365(11)
1.362(10)
1.389(14)
1.349(15)
C-16ꢀC-11ꢀC-12
C-16ꢀC-11ꢀC-7
C-12ꢀC-11ꢀC-7
O-2ꢀC-3¦ꢀC-3%
C-11ꢀC-12ꢀC-13
C-14ꢀC-13ꢀC-12
C-13ꢀC-14ꢀC-15
structure were performed with SHELX-86 [20]
and SHELX-97 [21]. The molecular diagram
was drawn with ORTEP II [22]. Selected bond
lengths and angles are presented in Table 2.
Table 3 contains the torsion angles relevant to
the configuration of the molecule.
Methyl3,3%-anhydro-2-O-benzoyl-4,6-O-ben-
zylidene-3-C-hydroxymethyl-h- -glucopyran-
D
oside (6).—The experimental procedure is the
same as described by Yoshimura et al. [5],
giving 6 as a syrup in 80% yield. [h]2D3+113°
(c 1.06, CHCl3); IR (CHCl3): w 1724 cm−1
(CꢁO), 1602 cm−1 (Ph); H NMR (300 MHz):
1
l 7.95–7.26 (m, 10 H, Ph), 5.49 (s, 1 H,
CHPh), 5.37 (d, 1 H, J1,2 3.66 Hz, H-2), 5.05
(d, 1 H, H-1), 4.28 (dd, 1 H, J6a,6e 10.17, J5,6e
4.35 Hz, H-6e), 3.99–3.89 (ddd, 1 H, H-5),
3.91 (d, 1 H, J4,5 9.45 Hz, H-4), 3.78 (t, 1 H,
J5,6a 9.9 Hz, H-6a), 3.35 (s, 3 H, OCH3), 3.12
(m, 2 H, H-3%a, H-3%b); 13C NMR: l 165.3
(C(ꢁO)O), 136.8, 133.4, 129.8, 129.1, 128.3,
128.1, 126.4 (Ph), 101.4 (CHPh), 98.3 (C-1),
75.6 (C-4), 69.0 (C-6), 68.0 (C-2), 63.4 (C-5),
57.3 (C-3), 55.5 (OCH3), 46.9 (C-3%).
Bond angles
C-1ꢀO-1ꢀC-10
O-3%ꢀC-3%ꢀC-3
O-3%ꢀC-3%ꢀC-3¦
C-3ꢀC-3%ꢀC-3¦
C-4ꢀO-6ꢀC-7
O-1ꢀC-1ꢀO-5
O-1ꢀC-1ꢀC-2
O-5ꢀC-1ꢀC-2
O-6ꢀC-4ꢀC-3
O-6ꢀC-4ꢀC-5
C-3ꢀC-4ꢀC-5
O-3ꢀC-3ꢀC-4
O-3ꢀC-3ꢀC-3%
C-4ꢀC-3ꢀC-3%
O-3ꢀC-3ꢀC-2
C-4ꢀC-3ꢀC-2
C-3%ꢀC-3ꢀC-2
C-2ꢀO-2ꢀC-3¦
C-7ꢀO-7ꢀC-6
C-1ꢀO-5ꢀC-5
O-2ꢀC-2ꢀC-1
O-2ꢀC-2ꢀC-3
C-1ꢀC-2ꢀC-3
O-7ꢀC-7ꢀO-6
O-7ꢀC-7ꢀC-11
O-6ꢀC-7ꢀC-11
C-11ꢀC-16ꢀC-15
O-5ꢀC-5ꢀC-6
O-5ꢀC-5ꢀC-4
113.2(6)
112.7(6)
109.5(6)
103.3(6)
111.8(6)
112.6(7)
107.4(6)
112.7(6)
108.5(5)
107.7(6)
113.2(6)
110.9(6)
109.9(6)
117.0(6)
107.1(5)
110.6(6)
100.5(5)
109.7(6)
110.0(8)
110.7(6)
112.4(6)
105.8(6)
114.4(6)
110.0(6)
106.6(7)
108.4(7)
121.2(9)
110.1(8)
107.2(7)
Methyl
4,6-O-benzylidene-3-C-(carboxy-
- glucopyranoside - 3%,2 - lactone
methyl) - h -
D
(8).—Lithium cyanide in DMF (0.5 M, 10.5
mL, 5.30 mmol) was added to a soln of 6 (527
mg, 1.32 mmol) in dry THF (2 mL) under
argon at rt. After heating under reflux for
12 h, the reaction mixture was cooled to rt,
hydrolyzed with water (15 mL) and extracted
with CHCl3 (3×15 mL). The organic phase
was dried (Na2SO4) and evaporated to dry-
ness. Column chromatography with 2:1
EtOAc–toluene gave methyl 4,6-O-benzyli-
dene-3-C-cyanomethyl-a- -glucopyranoside
D
(7) as a syrup (331 mg, 78%), which suffered
hydrolysis and spontaneous cyclization at rt to
give 8, isolated by column chromatography

10
A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
Table 3
Torsion angles (°) for 5
with 1:2 EtOAc–toluene as a solid (272 mg,
82%). mp 175–177 °C; [h]2D0 +124.7° (c 1,
CHCl3); IR (CHCl3): w 3568 cm−1 (OH), 1785
C-10ꢀO-1ꢀC-1ꢀO-5
C-10ꢀO-1ꢀC-1ꢀC-2
C-7ꢀO-6ꢀC-4ꢀC-3
C-7ꢀO-6ꢀC-4ꢀC-5
O-6ꢀC-4ꢀC-3ꢀO-3
C-5ꢀC-4ꢀC-3ꢀO-3
O-6ꢀC-4ꢀC-3ꢀC-3%
C-5ꢀC-4ꢀC-3ꢀC-3%
O-6ꢀC-4ꢀC-3ꢀC-2
C-5ꢀC-4ꢀC-3ꢀC-2
O-3%ꢀC-3%ꢀC-3ꢀO-3
C-3¦ꢀC-3%ꢀC-3ꢀO-3
O-3%ꢀC-3%ꢀC-3ꢀC-4
C-3¦ꢀC-3%ꢀC-3ꢀC-4
O-3%ꢀC-3%ꢀC-3ꢀC-2
C-3¦ꢀC-3%ꢀC-3ꢀC-2
O-1ꢀC-1ꢀO-5ꢀC-5
C-2ꢀC-1ꢀO-5ꢀC-5
C-3¦ꢀO-2ꢀC-2ꢀC-1
C-3¦ꢀO-2ꢀC-2ꢀC-3
O-1ꢀC-1ꢀC-2ꢀO-2
O-5ꢀC-1ꢀC-2ꢀO-2
O-1ꢀC-1ꢀC-2ꢀC-3
O-5ꢀC-1ꢀC-2ꢀC-3
O-3ꢀC-3ꢀC-2ꢀO-2
C-4ꢀC-3ꢀC-2ꢀO-2
C-3%ꢀC-3ꢀC-2ꢀO-2
O-3ꢀC-3ꢀC-2ꢀC-1
C-4ꢀC-3ꢀC-2ꢀC-1
C-3%ꢀC-3ꢀC-2ꢀC-1
C-6ꢀO-7ꢀC-7ꢀO-6
C-6ꢀO-7ꢀC-7ꢀC-11
C-4ꢀO-6ꢀC-7ꢀO-7
C-4ꢀO-6ꢀC-7ꢀC-11
C-1ꢀO-5ꢀC-5ꢀC-6
C-1ꢀO-5ꢀC-5ꢀC-4
O-6ꢀC-4ꢀC-5ꢀO-5
C-3ꢀC-4ꢀC-5ꢀO-5
O-6ꢀC-4ꢀC-5ꢀC-6
C-3ꢀC-4ꢀC-5ꢀC-6
C-11ꢀC-16ꢀC-15ꢀC-14
C-7ꢀO-7ꢀC-6ꢀC-5
O-5ꢀC-5ꢀC-6ꢀO-7
C-4ꢀC-5ꢀC-6ꢀO-7
C-15ꢀC-16ꢀC-11ꢀC-12
C-15ꢀC-16ꢀC-11ꢀC-7
O-7ꢀC-7ꢀC-11ꢀC-16
O-6ꢀC-7ꢀC-11ꢀC-16
O-7ꢀC-7ꢀC-11ꢀC-12
O-6ꢀC-7ꢀC-11ꢀC-12
C-2ꢀO-2ꢀC-3¦ꢀC-3%
O-3%ꢀC-3%ꢀC-3¦ꢀO-2
C-3ꢀC-3%ꢀC-3¦ꢀO-2
C-16ꢀC-11ꢀC-12ꢀC-13
C-7ꢀC-11ꢀC-12ꢀC-13
C-11ꢀC-12ꢀC-13ꢀC-14
C-12ꢀC-13ꢀC-14ꢀC-15
C-16ꢀC-15ꢀC-14ꢀC-13
68.2(9)
−167.2(8)
179.1(6)
−58.0(8)
−76.1(7)
164.4(6)
51.0(7)
−68.4(8)
165.3(5)
45.8(8)
1
cm−1 (C(ꢁO)O) and 1602 cm−1 (Ph); H
NMR (250 MHz): l 7.44–7.40 (m, 5 H, Ph),
5.58 (s, 1 H, CHPh), 4.92 (d, 1 H, J1,2 5.06 Hz,
H-1), 4.46 (d, 1 H, H-2), 4.35 (br d, 1 H, J6a,6e
5.58 Hz, H-6e), 3.82 (br s, 3 H, H-4, H-5,
H-6a), 3.42 (s, 3 H, OCH3), 3.09, 3.02 (1 H,
part A of AB system, JAB 17.63 Hz, H-3%a),
2.42, 2.35 (1 H, part B of AB system, H-3%b),
2.81 (s, 1 H, OH); 13C NMR: l 175.0 (C-3¦),
136.7, 129.6, 128.4, 126.2 (Ph), 102.6 (CHPh),
97.3 (C-1), 82.0 (C-4), 80.6 (C-2), 76.3 (C-3),
38.7(8)
−79.4(7)
−88.9(7)
153.0(6)
151.3(6)
33.3(7)
68.9 (C-6), 59.7 (C-5), 56.0 (OCH3), 38.1 (C-
+
’
3%); EIMS: m/z 322 (15, [M] ), 321 (5.7,
[M−H]+), 173 (30, [M−C6H5CHOCH2-
CHO]+), 149 (30, [C6H5CHOCH2CHO]+),
105 (100, [C6H5CO]+), 91 (45, [C6H5CH2]+),
77 (40, [C6H5]+), 51 (15, [C4H3]+); Anal.
Calcd for C16H18O7: C, 59.62; H, 5.63. Found:
C, 59.90; H, 5.75.
61.0(7)
−60.7(8)
−100.7(7)
24.8(8)
40.3(8)
164.9(6)
−80.4(8)
44.2(9)
Methyl 2,3¦-anhydro-4,6-O-benzylidene-3-
78.4(7)
C-[(2R)-/(2S)-2,2-dihydroxyethyl]-h- -gluco-
D
−160.7(6)
−36.4(7)
−157.3(6)
−36.4(8)
87.9(7)
−63.8(10)
178.9(7)
60.7(9)
pyranoside (9a,b) and methyl 4,6-O-benzyli-
dene-3-C-(2-hydroxyethyl)-h-
oside (10)
D
-glucopyran-
Method A. Diisobutylaluminum hydride
(DIBALH) in toluene (1 M, 1.7 mL, 1.7
mmol) was added dropwise to a soln of 8 (91
mg, 0.28 mmol) in 2:1 anhyd THF–toluene
(1.5 mL) at −78 °C under argon. After stir-
ring for 3 h at −78 °C and 1 h at −40 °C,
the reaction mixture was poured into a bipha-
sic system containing sodium potassium tar-
trate satd soln (1.5 mL) in CHCl3 (5 mL) and
stirred for 10 min. Chloroform (10 mL) was
then added and stirring was kept up for 2 h at
rt. Extraction with CHCl3 (3×15 mL), dry-
ness (Na2SO4) and evaporation afforded 10 as
a solid (48 mg, 52%) and 9a,b as a syrup (31
mg, 34%).
176.9(6)
−173.4(9)
68.4(7)
178.5(5)
−61.5(8)
59.5(10)
179.4(9)
−2.3(14)
64.1(12)
−179.1(8)
−61.9(13)
2.6(13)
−177.0(8)
85.8(9)
Method B. A soln of 8 (85 mg, 0.26 mmol)
in dry THF (4 mL) was added to a suspension
of LiAlH4 (30 mg, 0.79 mmol) in dry THF
(1.5 mL) at 0 °C under argon. The reaction
mixture was heated at 40 °C for 5 h and under
reflux for 1 h. The workup in method B was
followed affording 10 (71 mg, 82%) and 9a,b
(3.5 mg, 4%).
−32.5(10)
−93.8(9)
147.9(8)
−2.8(8)
−140.9(6)
−20.6(8)
−0.5(14)
179.1(8)
−1.8(16)
2.1(16)
Data for 9a,b: IR (KBr): w 3380 cm−1
−0.1(15)
1
(OH); H NMR (300 MHz): l 7.48–7.34 (m,

A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
11
tion mixture, which was then stirred for 30
min at rt. The aq phase was extracted with
CHCl3 (3×10 mL), dried (Na2SO4) and evap-
orated. The residue was purified by prepara-
tive TLC with 12:1 EtOAc–toluene to give 11
as a syrup (12 mg, 36%); [h]2D0 +67° (c 0.7,
10 H, Ph, Ph*), 5.78–5.64 (m, 2 H, H-3¦,
H*-3¦), 5.59 (s, 1 H, CHPh), 5.57 (s, 1 H,
CH*Ph), 4.83 (d, 1 H, J1,2 5.16 Hz, H*-1),
4.73 (d, 1 H, J1,2 5.19 Hz, H-1), 4.34–4.29 (m,
3 H, H-6e, H*6-e, H-2), 4.09 (d, 1 H, H*-2)
3.90–3.71 (m, 6 H, H-4, H-5, H-6a, H*-4,
H*-5, H*-6a), 3.50 (s, 3 H, OCH*3 ), 3.38 (s, 3
H, OCH3), 2.58 (dd, 1 H, J3%a,3¦ 5.76, J3%a,3%b
13.90 Hz, H-3%a), 2.44 (d, 1 H, J3¦,OH 4.47 Hz,
1
CHCl3); H NMR (300 MHz): l 7.39–7.30
(m, 5 H, Ph), 4.71 (d, 1 H, J1,2 5.16 Hz, H-1),
4.66, 4.62 (1 H, part A of AB system, JA,B
11.88 Hz, CH2Ph), 4.58, 4.54 (1 H, part B of
AB system, CH2Ph), 4.15–4.07 (m, 2 H, H-
3¦a, H-3¦b), 3.99 (dd, 1 H, J4,5 9.24, J4,OH 2.88
Hz, H-4), 3.89 (d, 1 H, H-2), 3.79–3.35 (m, 3
H, H-5, H-6e, H-6a), 3.43 (s, 3 H, OCH3),
2.96 (d, 1 H, OH-4), 2.44–2.34 (m, 1 H,
OH-3¦), 2.38 (dd, 1 H, J* 5.88, J3%a,3%b 14.82
3%a,3¦
Hz, H*-3%a), 2.14 (dd, 1 H, J*
5.82 Hz,
3%b,3¦
H*-3%b), 2.01 (d, 1 H, J3%a,3%b 13.90 Hz, H-3%b);
13C NMR: l 139.2, 136.9, 129.6, 129.3, 129.2,
128.5, 128.3, 126.2 (Ph, Ph*), 102.2 (CHPh,
C*HPh), 101.7 (C*-3¦), 100.9 (C-3¦), 98.5
(C*-1), 98.0 (C-1), 84.0 (C-2), 82.6 (C*-4),
82.1 (C*-2, C-4), 80.2 (C*-3), 78.8 (C-3), 69.1
(C-6, C*-6), 59.9 (C-5), 59.4 (C*-5), 55.6
(OCH3), 55.5 (OCH*3 ), 43.1 (C*-3%), 40.3 (C-
3%); Anal. Calcd for C16H20O7: C, 59.26; H,
6.21. Found: C, 59.49; H, 6.50.
13
H-3%a), 1.86–1.82 (m, 1 H, H-3%b); C NMR:
l 137.5, 128.5, 127.9, 127.6 (Ph), 99.0 (C-1),
81.8 (C-2), 81.0 (C-3), 73.8 (CH2Ph), 73.7
(C-4), 70.4 (C-6), 68.4 (C-3¦), 67.0 (C-5), 55.5
(OCH3), 33.7 (C-3%); HRMS: calcd for
C16H22O6 310.348, found: 310.142.
Methyl 2,3¦-anhydro-4,6-O-benzylidene-3-
Data for 10: mp 124–125 °C; [h]2D0+48.4°
(c 1.0, CHCl3); IR (KBr): w 3328 cm−1 (OH);
1H NMR (300 MHz): l 7.48–7.34 (m, 5 H,
Ph), 5.53 (s, 1 H, CHPh), 4.77 (d, 1 H, J1,2
3.81 Hz, H-1); 4.32 (dd, 1 H, J5,6e 4.11, J6a,6b
9.61 Hz, H-6e), 4.03–3.84 (m, 2 H, H-3¦a,
H-3¦b), 3.81–3.60 (m, 4 H, H-2, H-4, H-5,
H-6a), 3.42 (s, 3 H, OCH3), 2.29–2.35 (m, 2
H, H-3%a, H-3%b); 13C NMR: l 137.1, 129.2,
126.3, 126.2 (Ph), 101.9 (CHPh), 100.8 (C-1),
84.4 (C-4), 75.0 (C-2), 74.6 (C-3), 69.2 (C-6),
61.5 (C-5), 58.6 (C-3¦), 56.0 (OCH3), 32.8
C-(2-hydroxyethyl)-h- -glucopyranoside (12).
D
—Triphenylphosphine (73 mg, 0.28 mmol)
,
and powdered 4 A molecular sieves (100 mg)
were added to the soln of 10 (91 mg, 0.28
mmol) in dry CHCl3 (5 mL) under argon.
After cooling at 5 °C, DEAD (0.15 mL, 0.92
mmol) was added dropwise and the reaction
mixture was stirred at 5 °C for 2.5 h. Filtra-
tion, evaporation and column chromatogra-
phy with 2:1 EtOAc–toluene afforded 12 as a
solid (70 mg, 82%); mp 133–135 °C; [h]D20
+96.5° (c 1.0, CHCl3); IR (CHCl3): w 3320
+
’
1
cm−1 (OH); H NMR (300 MHz): l 7.49–
(C-3%); EIMS: m/z 326 (0.3, [M] ), 307 (2.2,
+
+
’
[M−H−H2O] ), 294 (4.4; [M−CH3OH] ),
281 (3.3, [M−CH2CH2OH]+), 188 (13.2,
[M−H−C6H5CHO−CH2OH]+), 179 (21;
[C10H11O3]+), 149 (26, [C6H5CHOCH2CHO]+),
107 (97, [C6H5CHOH]+), 106 (47, [C6H5-
7.37 (m, 5 H, Ph), 5.58 (s, 1 H, CHPh), 4.75
(d, 1 H, J1,2 4.17 Hz, H-1), 4.36–4.15 (m, 3 H,
H-6e, H-3¦a, H-3¦b), 4.01 (d, 1 H, H-2), 3.91
(d, 1 H, J4,5 8.88 Hz, H-4), 3.83–3.72 (m, 2 H,
H-5, H-6a), 3.40 (s, 3 H, OCH3), 2.54–2.42
(m, 1 H, H-3%a), 1.94–1.88 (m, 1 H, H-3%b);
13C NMR: l 137.1, 129.2, 128.3, 126.2 (Ph),
102.3 (CHPh), 99.3 (C-1), 83.0 (C-4), 82.6
(C-2), 79.8 (C-3), 69.3 (C-6), 69.1 (C-3¦), 59.6
(C-5), 55.5 (OCH3), 33.6 (C-3%); EIMS: m/z
+
’
+
CHO] ), 105 (100, [C6H5CO] ), 45 (32,
[CH2CH2OH]+), 31 (16, [CH2OH]+); Anal.
Calcd for C16H22O7: C, 58.88; H, 6.79. Found:
C, 58.72; H, 6.79.
Methyl 2,3¦-anhydro-6-O-benzyl-3-C-(2-hy-
+
+
’
droxyethyl)-h- -glucopyranoside (11).—Tri-
D
308 (14.3, [M] ); 307 (43, [M−H] ), 280 (79,
+
+
’
ethylsilane (0.1 mL, 0.63 mmol) was added to
a soln of 9a,b (35 mg, 0.11 mmol) in MeCN (1
mL) under argon at −30 °C followed by ad-
dition of BF3·Et2O (0.1 mL, 0.81 mmol). After
90 min at −30 °C, a satd soln of potassium
carbonate (1 mL) was poured into the reac-
[M−C2H4] ), 277 (21, [M−OCH3] ), 276
+
+
’
(54, [M−CH3OH] ); 229 (36, [M−C6H7] ),
205 (15, [M−C4H7O3]+), 149 (15, [C6H5-
CHOCH2CHO]+), 107 (100, [C6H5CHOH]+),
+
+
’
106 (20, [C6H5CHO] ), 105 (65, [C6H5CO] ),
91 (55, [C6H5CH2]+), 79 (30, [C6H7]+), 77 (40,

12
A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
[C6H5]+); Anal. Calcd for C16H20O6: C, 62.33;
H, 6.54. Found: C, 62.60; H 6.83.
4.88 (d, 1 H, J1,2 5.01 Hz, H-1), 4.84 (br s, 1
H, H-3%), 4.41 (d, 1 H, H-2), 4.31 (dd, 1 H,
J5,6e 3.30, J6a,6e 10.59 Hz, H-6e), 3.87–3.74 (m,
3 H, H-4, H-5, H-6a), 3.37 (s, 3 H, OCH3),
3.20 (br s, 1 H, OH-3%), 1.80 (s, 1 H, OH-3);
13C NMR: l 174.7 (C-3¦), 136.5, 129.3, 128.4,
126.1 (Ph), 102.3 (CHPh), 96.8 (C-1), 81.9
(C-4), 77.8 (C-2), 75.2 (C-3), 68.9 (C-6), 68.6
(C-3%), 59.7 (C-5), 55.9 (OCH3); EIMS: m/z
Methyl 2,3¦-anhydro-4,6-O-benzylidene-3-
O- acetyl - 3 - C- (2 - hydroxyethyl) - h - - gluco-
D
pyranoside (13).—Acetic anhydride (26 mL)
and 4-dimethyl aminopyridine (DMAP) (cata-
lytic amount) were added to a soln of 12 (36
mg, 0.12 mmol) in pyridine (0.5 mL) and the
reaction mixture was stirred at rt for 3 h.
Column chromatography eluted with 1:5
EtOAc–toluene gave 13 as a syrup (38.6 mg,
94%); [h]2D0+37.6° (c 0.9, CHCl3); IR (KBr): w
+
+
’
338 (40, [M] ), 337 (27, [M−H] ), 189 (25,
[M−C6H5CHOCH2CHO]+), 149 (36, [C6H5-
CHOCH2CHO]+), 107 (86, [C6H5CHOH]+),
+
+
’
1
1724 cm−1 (CꢁO); H NMR (300 MHz):l
106 (29, [C6H5CHO] ), 105 (100, [C6H5CO] ),
91 (43, [C6H5CH2]+), 77 (36, [C6H5]+);
LSIMS: m/z 339 (100; [M+H]+) 233 (31,
[M+H−C6H5CHO]+) 107 (22, [C6H5CH-
OH]+); HRMS: calcd for C16H18O8 338.311,
found: 338.100.
7.50–7.26 (m, 5 H, Ph), 5.57 (s, 1 H, CHPh),
4.90–4.86 (m, 3 H, H-1, H-2, H-4), 4.29 (dd, 1
H, J6a,6e 8.07 Hz, J5,6e 5.13 Hz, H-6e), 4.21 (m,
1 H, JAB −7.33, JAC 9.74, JAD 1.88 Hz, A),
4.04 (m, 1 H, JBC 9.88, JBD 7.00 Hz, B),
3.88–3.82 (m, 2 H, H-5, H-6a), 3.42 (s, 3 H,
OCH3), 2.53 (m, 1 H, JCD −13.63 Hz, C),
2.20 (m, 1 H, D), 2.07 (s, 3 H, CH3); 13C
NMR: l 171.2 (CꢁO), 137.2, 129.1, 128.3,
126.2 (Ph), 101.8 (CHPh), 96.6 (C-1), 88.9
(C-3), 78.8, 76.5 (C-2, C-4), 69.2 (C-6), 68.4
(C-3¦), 60.4 (C-5), 55.6 (OCH3), 32.3 (C-3%),
22.5 (CH3); HRMS: calcd for C18H22O7
350.365, found: 350.136.
Methyl 2-O-benzoyl-4,6-O-benzylidene-h-
D
-
ribo-hexopyranosid-3-ulose (16).—A soln of
methyl 2-O-benzoyl-4,6-O-benzylidene-a- -
D
glucopyranoside [23] (1.58 g, 4.1 mmol) in dry
CH2Cl2 (12 mL) was added dropwise at rt to
the suspension of PCC (2.02 g, 9.4 mmol) and
,
powdered 3 A molecular sieves (3.65 g) in dry
CH2Cl2 (18 mL). The mixture was stirred for
15 h at rt. Celite (2.0 g) was added to the
reaction mixture, which was then stirred for
20 min. The solids were filtered off and the
filtrate evaporated to dryness. The residue was
dissolved in EtOAc (200 mL) and the soln was
filtered through Florisil (15 g). Evaporation of
the solvent gave 16 (1.46 g, 93%) as a solid;
mp 210–213 °C, lit. 211–213 °C [18]; [h]D20
+69.6° (c 1.02, CHCl3); IR (CHCl3): w 1764
Methyl
boxy)hydroxymethyl] - h -
4,6-O-benzylidene-3-C-[(R)-(car-
- glucopyranoside-
D
3%,2-lactone (14).—A soln of 8 (80 mg, 0.25
mmol) in dry THF (2 mL) was added drop-
wise to a soln of lithium diisopropyl amine
(LDA) [14] (0.6 M, 3 mL) at −78 °C under
argon and the mixture was stirred for 50 min.
The complex MoO5·py·HMPA [14] (650 mg,
1.49 mmol) was then added and the reaction
mixture was stirred for 3 h at −78 °C. When
the temperature reached 25 °C, a satd aq
NaHSO3 soln (3 mL) was poured into the
reaction mixture, which was stirred for 20
min. After extraction with CHCl3 (3×25
mL), the organic layers were dried (Na2SO4)
and evaporated. Column chromatography
eluted with 1:2 EtOAc–toluene followed by
preparative TLC with the same solvent system
afforded 14 as a syrup (22 mg, 0.06 mmol,
50% on the basis of the reacted deoxylactone
8, recovered in 47.5% yield); [h]2D0+114.6° (c
0.5, CHCl3); IR (CHCl3): w 3440 (OH) and
1
(CꢁO) and 1726 (CꢁO); H NMR (300 MHz):
l 8.07–7.27 (m, 10 H, Ph), 5.56 (d, 1 H, J1,2
4.68 Hz, H-2), 5.53 (s, 1 H, CHPh), 5.27 (d, 1
H, H-1), 4.41–4.34 (m, 2 H, H-4, H-6e), 4.16–
4.08 (ddd, 1 H, J5,6e 4.56, J5,6a 10.23, J4,5 10.08
Hz, H-5), 3.92 (t, 1 H, J6a,6e 10.26 Hz, H-6a),
3.41 (s, 3 H, OCH3); 13C NMR: l 191.9
(CꢁO), 165.6 (CꢁO), 136.3, 133.6, 130.1, 129.2,
128.3, 128.2, 126.3 (Ph), 101.8 (CHPh), 101.3
(C-1), 82.0 (C-4), 74.8 (C-2), 69.3 (C-6), 65.4
(C-5); 55.6 (OCH3).
Methyl 2-O-benzoyl-4,6-O-benzylidene-3-C-
[(Z) - (ethoxycarbonyl)methylene] - h -
D
- ribo-
hexopyranoside (17) and methyl 2-O-benzoyl-
4,6-O-benzylidene-3-C-[(E)-(ethoxycarbonyl)-
1
1798 cm−1 (CꢁO); H NMR (300 MHz): l
methylene]-h-
D
-ribo-hexopyranoside (18).—A
7.42–7.30 (m, 5 H, Ph), 5.52 (s, 1 H, CHPh),
soln of [(ethoxycarbonyl)methylene]triphenyl-

A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
13
mL) were added, and within 30 min the com-
plex was cleaved to give an orange soln. The
mixture was extracted with CHCl3 (3×25
mL), dried (Na2SO4) and evaporated to give
19a,b as a syrup (479 mg, 100%).
phosphorane (3.60 g, 10.4 mmol) in dry
CHCl3 (40 mL) was added at rt to a soln of 16
(1.0 g, 2.6 mmol) in dry CHCl3 (8 mL). The
mixture was stirred under reflux for 5.5 h.
Evaporation of the solvent and purification by
column chromatography eluted with 1:5
EtOAc–hexane afforded 17 and 18 in a 7:3
ratio as a syrup (1.07 g, 88%); IR (CHCl3): w
Method B. Compounds 17,18 (152 mg, 0.33
mmol) and 4-methylmorpholine-N-oxide (94
mg, 0.8 mmol) were dissolved in 8:1 acetone–
water (3.04 mL). A catalytic amount of os-
mium tetraoxide was added, and the reaction
mixture was stirred overnight at rt. The soln
was filtered and extracted with CHCl3 (3×15
mL). The organic phase was dried (Na2SO4),
filtered and evaporated to give 19a,b as a
syrup (109 mg, 66%).
1
1718 (CꢁO), 1606 (CꢁC); 1590 cm−1 (Ph); H
NMR (300 MHz) data for 17: l 8.09–7.36 (m,
10 H, Ph), 6.18 (t, 1 H, J3%,4 1.47 Hz, H-3%),
5.92 (t, 1 H, J2,3% 2.94 Hz, H-2), 5.64 (s, 1 H,
CHPh), 4.93 (d, 1 H, J1,2 4.41 Hz, H-1),
4.36–4.31 (m, 1 H, H-6e), 4.11 (dd, 1 H, J4,5
8.82 Hz, H-4), 4.01–3.97 (m, 1 H, H-5), 3.88
(m, 1 H, H-6a), 3.80–3.73 (m, 2 H, CH2ꢀEt),
Methyl 4,6-O-benzylidene-3-C-[(R)-/(S)-1,2-
dihydroxyethyl]-h- -glucopyranoside (20a,b),
D
1
3.44 (s, 3 H, OCH3) 0.98 (t, 3 H, CH3ꢀEt); H
methyl 2,3¦-anhydro-4,6-O-benzylidene-3-C-
NMR (300 MHz) data for 18: l 8.09–7.36 (m,
10 H, Ph), 6.09 (t, 1 H, J3%,4 1.45 Hz, H-3%),
5.92 (t, 1 H, J2,3% 2.94 Hz, H-2), 5.59 (s, 1 H,
CHPh), 5.06 (d, 1 H, J1,2 3.66 Hz, H-1),
4.36–4.31 (m, 1 H, H-6e), 4.11 (dd, 1 H, J4,5
8.82 Hz, H-4), 4.01–3.97 (m, 1 H, H-5), 3.88
(m, 1 H, H-6a), 3.80–3.73 (m, 2 H, CH2ꢀEt),
3.44 (s, 3 H, OCH3) 0.98 (t, 3 H, CH3ꢀEt); 13C
NMR data for 17: l 167.5 (CꢁO), 165.3
(CꢁO), 136.5 (Ph), 135.3 (C-3), 133.7, 130.2,
129.4, 129.1, 128.4, 126.4 (Ph), 114.5 (C-3%),
101.9 (CHPh), 98.7 (C-1), 77.5 (C-4), 70.6
(C-2), 69.9 (C-6), 64.8 (C-5); 60.9 (CH2ꢀEt),
55.8 (OCH3), 13.9 (CH3ꢀEt); 13C NMR data
for 18: l 167.9 (CꢁO), 165.0 (CꢁO), 137.1
(Ph), 135.3 (C-3), 133.8, 130.1, 129.2, 128.7,
128.2, 126.5 (Ph), 114.2 (C-3%), 101.8 (CHPh),
98.5 (C-1), 78.8 (C-4), 70.2 (C-2), 69.3 (C-6),
[(1S,2R)-/(1S,2S)-1,2,2-trihydroxyethyl]-h-
D
-
glucopyranoside (21a,b) and methyl 2,3¦-anhy-
dro-4,6-O-benzylidene-3-C-[(1R,2R)-1,2,2-
trihydroxyethyl]-h- -glucopyranoside (22)
D
Method A. A soln of 19a,b (250 mg, 0.51
mmol) in dry THF (9 mL) was added drop-
wise to a suspension of LiAlH4 (40.6 mg, 1.07
mmol) in dry THF (2 mL), at 0 °C under
argon. The temperature was raised to rt and
the mixture was then stirred for 3 h 30 min.
The reaction mixture was poured into a bipha-
sic system of sodium potassium tartrate aq
satd soln (15 mL) and CHCl3 (15 mL) at 0 °C
and the mixture was stirred vigorously for 2 h
at rt. After extraction with 5:1 CHCl3–THF
(3×30 mL), the organic phase was dried
(Na2SO4) and evaporated. Column chro-
matography with 2:1 AcOEt–toluene afforded
20a,b (63.8 mg, 36%) and the secondary prod-
ucts methyl 2,3¦-anhydro-4,6-O-benzylidene-
3-C-[(1S,2R)-/(1S,2S)-1,2,2-trihydroxyethyl]-
64.8 (C-5); 60.8 (CH2ꢀEt), 55.7 (OCH3), 13.8
+
’
(CH3ꢀEt); EIMS: m/z 454 (0.4, [M] ), 394
+
’
(36, [M−OCHOCH3] ); 289 (23, [M−
a- -glucopyranoside (21a,b) (29.4 mg, 18%)
D
OCHOCH3−COC6H5]+); 183 (27, [M−
and methyl 2,3¦-anhydro-4,6-O-benzylidene-3-
OCHOCH3−COC6H5−C6H5CHO]+); 149
C-[(1R,2R)-1,2,2-trihydroxyethyl]-a-
D
-gluco-
(19,
[C6H5CH2]+).
[C6H5CHOCH2CHO]+);
91
(100,
pyranoside (22) (46 mg, 27%).
Method B. A soln of 19a,b (250 mg, 0.51
mmol) in dry THF (9 mL) was added drop-
wise to a suspension of LiAlH4 (116 mg, 3.06
mmol) in dry THF (2 mL) at 0 °C under
argon. The mixture was stirred under reflux
for 24 h. After the workup described above,
column chromatography with 2:1 EtOAc–
toluene afforded 20a,b (84 mg, 48%), 21a,b (24
mg, 14%) and 22 (15 mg, 9%).
Methyl 2-O-benzoyl-4,6-O-benzylidene-3-C-
[(R)- and (S)-(ethoxycarbonyl)hydroxymethyl]-
h-
D
-glucopyranoside (19a,b)
Method A. Osmium tetraoxide (250 mg,
0.98 mmol) was added to a soln of 17,18 (446
mg, 0.98 mmol) in dry pyridine (4 mL), and
the mixture was stirred at rt for 2.5 h. A satd
aq soln of NaHSO3 (10 mL) and pyridine (4

14
A. Rauter et al. / Carbohydrate Research 325 (2000) 1–15
13
Data for 20a,b: IR (KBr): w 3456 cm−1
Hz, H-6a); 3.51 (s, 3 H, OCH3), C NMR: l
136.9, 129.5, 128.3, 126.4 (Ph), 106.8 (C-3¦),
102.9 (CHPh), 97.8 (C-1), 83.4 (C-2), 82.7
(C-4), 79.2 (C-3%), 78.9 (C-3), 69.7 (C-6), 60.3
(C-5), 55.7 (OCH3); HRMS: calcd for
C16H20O8 340.327, found: 340.116.
1
(OH); H NMR (CDCl3/D2O) (300 MHz) of
20a: l 7.46–7.34 (m, 5 H, Ph), 5.46 (s, 1 H,
CHPh), 4.79 (d, 1 H, J1,2 3.63 Hz, H-1), 4.58
(br s, 1 H, H-3%), 4.33 (dd, 1 H, J5,6e 5.01, J6a,6e
10.47 Hz, H-6e), 4.24 (dd, 1 H, J3¦a,3¦b 11.97,
J3%a,3¦a 3.3 Hz, H-3¦a); 3.92–3.84 (m, 2 H,
H-3¦b, H-5), 3.69 (d, 1 H, H-2), 3.66–3.52 (m,
2 H, H-4, H-6a), 3.49 (s, 3 H, OCH3); 13C
NMR of 20a: l 135.5, 128.1, 127.3, 124.3
(Ph), 101.3 (CHPh), 99.9 (C-1), 85.6 (C-4),
74.3 (C-3), 73.1 (C-2), 71.0 (C-3%), 68.2 (C-6),
62.7 (C-3¦), 60.7 (C-5), 54.8 (OCH3); EIMS:
4. Supplementary material
Tables of atomic coordinates, bond lengths,
bond angles, isotropic and anisotropic dis-
placement parameters have been deposited
with the Cambridge Crystallographic Data
Centre. These tables may be obtained on re-
quest from The Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road,
Cambridge, CB2 1EZ, UK.
+
’
m/z 342 (0.2, [M] ), 311 (7.3, [M−
CH2OH]+); 282 (5.9, [M−CHOHCH2OH]+);
+
’
281 (8.8, [M−H−CHOHCH2OH] ); 263
(5.9, [M−CHOHCH2OH−H2O]+); 179 (8.8,
[C10H11O3]+); 149 (30, [C6H5CHOCH2CH-
O]+), 107 (71, [C6H5CHOH]+), 106 (38,
+
+
’
[C6H5CHO] ); 105 (43, [C6H5CO] ), 87 (75,
[C4H7O2]+), 31 (100, [OCH3]+); HRMS: calcd
for C16H22O8 342.348, found: 342.131.
Acknowledgements
Data for 21a,b: IR (KBr): w 3396 cm−1
(OH); H NMR (300 MHz) of 21a: l 7.48–
We are grateful to the European Economic
Community for financial support (project
SCI-CT91-0723) and to the Junta Nacional de
Investigac¸a˜o Cient´ıfica e Tecnolo´gica for a
research grant. We thank Professor Pierre
Sinay¨ for sending us a sample of 3, Dr
Joaquim Marc¸alo and Dr Conceic¸a˜o Oliveira
for the high-resolution mass spectra, and Dr
Albertino Figueiredo and Dr Fernando Matos
for running the NMR spectra.
1
7.45 (m, 5 H, Ph), 5.56 (s, 1 H, CHPh), 5.41
(d, 1 H, J3%,3¦ 5.55 Hz, H-3¦), 4.85 (d, 1 H, J1,2
5.13 Hz, H-1), 4.66 (d, 1 H, H-3%), 4.34 (m, 1
H, H-6e), 4.22 (d, 1 H, H-2), 3.84–3.74 (m, 3
H, H-4, H-5, H-6a), 3.44 (s, 3 H, OCH3); 21b:
l 7.48–7.35 (m, 5 H, Ph), 5.56 (s, 1 H,
CHPh), 5.26 (d, 1 H, J3%,3¦ 4.19 Hz, H-3¦); 4.77
(d, 1 H, J1,2 5.13 Hz, H-1), 4.44 (d, 1 H, H-3%),
4.34 (m, 1 H, H-6e), 4.29 (d, 1 H, H-2),
3.84–3.74 (m, 3 H, H-4, H-5, H-6a), 3.42 (s, 3
H, OCH3); 13C NMR of 21a: l 136.9, 129.3,
128.4, 126.0 (Ph), 105.1 (C-3¦), 102.2 (CHPh),
98.3 (C-1), 82.7 (C-4), 81.7 (C-2), 78.6 (C-3%),
77.2 (C-3), 69.1 (C-6), 59.8 (C-5), 55.6
(OCH3); 21b: l 136.7, 129.3, 128.4, 126.0 (Ph),
102.2 (CHPh), 98.0 (C-1), 97.7 (C-3¦), 80.2
(C-2), 70.5 (C-3%), 69.0 (C-6), 59.3 (C-5), 82.7
(C-4), 77.2 (C-3), 55.6 (OCH3); HRMS: calcd
for C16H20O8 340.327, found: 340.116.
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