Synthesis of seven- and eight-membered carbasugar analogs via ring-closing metathesis and their inhibitory activities toward glycosidases

Article abstract of DOI:10.1016/S0957-4166(02)00654-7

An expeditious and efficient synthesis of new enantiopure polyhydroxylated seven- and eight-membered carbocycles is described starting from 2,3,5-tri-O-benzyl-D-arabinose. The key cyclization step involves ring closing metathesis of 1,8- and 1,9-dienes using Grubbs' catalyst. All of the new carbasugar analogs synthesized were evaluated as glycosidase inhibitors. Contrary to our expectations, (1S,2S,3R,4R,5R)-1-(hydroxymethyl)-cyclohepta-1,2,3,4,5-pentol which has the β-D-mannopyranose configuration for C(1)-C(5) inhibits α- and β-glucosidases, whereas its diepimer (1S,2S,3R,4S,5S)-1-(hydroxymethyl)-cyclohepta-1,2,3,4,5-pentol, which has the α-D-glucopyranose configuration, is not recognised by these enzymes.

Full text of DOI:10.1016/S0957-4166(02)00654-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2553–2565
Synthesis of seven- and eight-membered carbasugar analogs via
ring-closing metathesis and their inhibitory activities toward
glycosidases
Yves Ble´riot,a Andre´ Giroult,a Jean-Maurice Mallet,a Eliazar Rodriguez,b Pierre Vogelb and
Pierre Sinay¨a,*
aEcole Normale Supe´rieure, De´partement de Chimie, UMR 8642, 24 rue Lhomond, 75231 Paris Cedex 05, France
bInstitut de Chimie Mole´culaire et Biologique, Ecole Polytechnique Fe´de´rale de Lausanne, BCH, CH-1015 Lausanne, Switzerland
Received 24 September 2002; accepted 11 October 2002
Abstract—An expeditious and efficient synthesis of new enantiopure polyhydroxylated seven- and eight-membered carbocycles is
described starting from 2,3,5-tri-O-benzyl-D-arabinose. The key cyclization step involves ring closing metathesis of 1,8- and
1,9-dienes using Grubbs’ catalyst. All of the new carbasugar analogs synthesized were evaluated as glycosidase inhibitors.
Contrary to our expectations, (1S,2S,3R,4R,5R)-1-(hydroxymethyl)-cyclohepta-1,2,3,4,5-pentol which has the b- -mannopyranose
D
configuration for C(1)–C(5) inhibits a- and b-glucosidases, whereas its diepimer (1S,2S,3R,4S,5S)-1-(hydroxymethyl)-cyclohepta-
1,2,3,4,5-pentol, which has the a-D-glucopyranose configuration, is not recognised by these enzymes. © 2002 Elsevier Science Ltd.
All rights reserved.
1. Introduction
cycloheptanic and cyclooctanic carbasugar analogs.
The new spatial distribution of the hydroxyl groups and
the increased flexibility of such structures should allow
an enhanced adaptability of these carbocycles in the
active site of the carbohydrate processing enzymes. Our
route enables us to obtain various carbasugars to study
their inhibitory activities towards glycosidases.
The conversion of carbohydrates into carbocycles is a
major task and has been the subject of many studies.1
Interest in this class of compounds is high due to the
fact that many biologically important molecules and
natural products contain a polyhydroxylated carbocy-
cle.2 Various methods are already available for the
construction of functionalized five- and six-membered
rings from sugars3 but only a few approaches have been
reported for the synthesis of seven-4 and eight-mem-
bered ring cyclitols.5
2. Results
The envisaged retrosynthetic approach starts from
readily available 2,3,5-tri-O-benzyl-D
-arabinose7 and
As part of our ongoing project on the synthesis of new
carbohydrate carbocyclic mimetics,6 we would like to
disclose herein our approach for the synthesis of new
involves the carbocyclization of 1,8-diene or 1,9-diene
using the ring-closing metathesis methodology (Scheme
1). A similar strategy has been reported by Eustache et
Scheme 1. Retrosynthetic analysis.
* Corresponding author. Tel.: +33(0)144323389; fax: +33(0)144323397; e-mail: pierre.sinay@ens.fr
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00654-7

2554
Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
al. for the synthesis of five-membered branched cyclitols
Our approach starts with the use of compound 212
which could be prepared through Wittig olefination of
and valiolamine.8
2,3,5-tri-O-benzyl-
-arabinose 1.7 The alcohol 2 was
D
For some time we have been interested in the powerful
ring-closing metathesis (RCM) methodology which has
become the method of choice for carbonꢀcarbon bond
construction in particular in carbohydrate chemistry.9
The main advantages of RCM are its wide applicability
and its remarkable tolerance to functional groups.10
Preparation of cycloheptanols using RCM is well docu-
mented.4 To our knowledge, only a few examples
describe the synthesis of cyclooctanols,5 probably due
to the unfavorable thermodynamic factors associated
with cyclooctane chemistry.11
then oxidized with PCC to give the known ketone 313 in
90% yield. Compound 3 was reacted with an excess of
butenyl- or pentenylmagnesium bromide in THF at 0°C
to furnish the 1,8-diene-ols 4a and 4b and 1,9-diene-ols
5a and 5b, respectively, in 64–70% yield as inseparable
mixtures of diastereomers and in a 1/1 ratio (Scheme 2).
The key carbocyclization step was then examined, the
results being summarized in Table 1. Cyclization of the
1,8-diene-ols 4a and 4b using Grubbs catalyst 6 in
dichloromethane afforded cycloheptenes 8 and 9 in 60%
Scheme 2. Synthesis of dienes 4a, 4b, 5a and 5b. Reagents and conditions: (i) Reference 7; (ii) PCC, molecular sieves, DCM, ether;
(iii) CH2ꢁCH(CH2)3Br or CH2ꢁCH(CH2)2Br, Mg, Et2O, THF.
Table 1. RCM of cycloheptenes 4a, 4b and cyclooctenes 5a, 5b, 12a, 12b using catalysts 6 and 7

Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
2555
The next step was the functionalization of the ethylenic
bond present in the cycloheptenes and cyclooctenes.
yield (entry 1). When dienes 4a and 4b were subjected
to RCM conditions using catalyst 7,14–16 the
diastereomeric cycloheptenes 8 and 9 were obtained in
almost quantitative yield (entry 2).
19
syn-Dihydroxylation of cycloheptene 8 using OsO4
afforded triols 15 and 16 in 82% yield and in a 3/7
ratio. Subsequent hydrogenolysis of the benzyl groups
afforded cyclitols 19 and 20 in quantitative yield. The
same sequence was uneventfully applied to cyclohep-
tene 9 to give cyclitols 21 and 22 (Scheme 3).
When the homologous 1,9-diene-ols 5a and 5b were
subjected to the RCM procedure, disappointing results
were obtained: cyclization using Grubbs’ catalyst 6
under various conditions (temperature, solvent, drop-
wise addition of the catalyst) afforded diastereomeric
cyclooctenes 10 and 11 in a modest 29% yield (entry 3)
along with recovered starting material (40%). Similar
results have been observed previously by Bourgeois et
al. in their synthesis of the B–C ring system of taxol.17
Surprisingly, use of catalyst 7 failed to effect any reac-
tion (entry 4). We postulated that the low reactivity of
the 1,9-diene-ols with the ruthenium-based catalysts 6
and 7 could be due to chelation of the oxygen of the
free tertiary alcohol group with ruthenium as previ-
ously observed in others cases.18 To overcome this
problem, the tertiary alcohol in 5a and 5b was pro-
tected as its tert-butyldimethylsilyl ether to afford 12a
and 12b. To our great satisfaction, when 12a and 12b
were submitted to RCM reaction in the presence of
Grubbs’ catalyst 6 in toluene at 90°C for 3 days,
cyclooctenes 13 and 14 were obtained in a 86% overall
yield (entry 5). Subsequent desilylation with TBAF in
THF afforded the corresponding cyclooctenes 10 and
11 in high yield. Thin layer chromatography monitor-
ing of the RCM reaction indicated that the
diastereomeric 1,8-dienes and 1,9-dienes cyclized at a
comparable rate and 1:1 diastereomeric mixtures were
obtained in each case. Use of the modified Grubbs’
catalyst 7 with the fully protected dienes 12a and 12b
was again unsuccessful (entry 6). The lack of reaction
observed with cyclooctenes 5a, 5b, 12a and 12b in the
presence of catalyst 7 is in marked contrast with previ-
ously reported results.5b
The same sequence was then applied to cyclooctenes 10
and 11 affording cyclitols 27–30 (Scheme 4).
2.1. Structural assignments
The stereochemistry of the carbon C-5 of cycloheptenes
8 and 9 and cyclooctenes 10 and 11 was deduced from
NOE measurements performed on each cycloalkene
which indicated that compounds 8 and 10 had the 5S
configuration and compounds 9 and 11 the 5R configu-
ration (Fig. 1).
The stereochemistry of the syn-dihydroxylation per-
formed on cycloheptenes and cyclooctenes was deduced
from the coupling constants observed between H-1, H-2
and H-3 in compounds 15, 16, 17, 18, 23, 24, 25 and 26.
To unambiguously confirm the structural assignment of
our conformationally flexible carbocycles, their confor-
mation was locked in order to obtain crystals suitable
for X-ray crystallographic analysis. Thus, compound 25
was converted in three steps into the crystalline triace-
tonide 3120 (Scheme 5 and Fig. 2).
The new synthetic polyhydroxylated carbocycles were
then evaluated as glycosidase inhibitors.
2.2. Glycosidase inhibition
Cyclic polyols such as epoxides of conduritols can be
selective inhibitors of glycosidases.21 Recently, it has
Scheme 3. Synthesis of the polyhydroxylated cycloheptanes 19–22. Reagents and conditions: (i) OsO4, NMO, tBuOH, acetone,
H2O; (ii) H2, Pd/C, MeOH, AcOEt.

2556
Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
Scheme 4. Synthesis of the polyhydroxylated cyclooctanes 27–30. Reagents and conditions: (i) TBAF, THF; (ii) OsO4, NMO,
tBuOH, acetone, H2O; (iii) H2, Pd/C, MeOH, AcOEt.
Figure 1. NOE observed for cycloheptenes 8 and 9 and cyclooctenes 10 and 11 (for reasons of commodity atom numbering does
not follow IUPAC numbering rules).
inhibitor of b-glucosidase.26 This discovery has stimu-
lated the synthesis of several stereomers and analogs of
cyclophellitol and their glycosidase inhibitory activities
have been evaluated.27
By analogy with the above, we envisioned that polyols
19 and 27 with the a-D-glucopyranose configuration for
Scheme 5. Synthesis of triacetonide 31. Reagents and condi-
tions: (i) acetone, 2,2-dimethoxypropane, CSA, 78%; (ii) H2,
10% Pd/C, CH3OH, EtOAc; (iii) acetone, 2,2-dimethoxy-
propane, CSA, 78%.
C(1), C(2), C(3), C(4), C(5) could be potential a-glu-
cosidase inhibitors. This was not the case. To our
surprise, compound 20 with the b-D-mannopyranose
configuration is a moderate inhibitor of a-glucosidase
(maltase) from yeast (81% at 1 mM), isomaltase from
baker’s yeast (78% at 1 mM) and of b-glucosidase from
almonds (79% at 1 mM). It is also a weak inhibitor of
b-galactosidase from both Aspergillus oryzae and jack
beans, and also inhibits b-glucosidase from Caldocellum
saccharolyticum and b-xylosidase from Aspergillus niger
(Table 2).
been shown that a bicyclo-[4.3.0]-nonane-2,3,4,5,6,
7,8,9-heptol inhibits a-glucosidases.22 Conduritol A, a
cyclohex-5-ene-1,2,3,4-tetrol isolated from the leaves of
Gymnema sylvestre is an hypoglycemia agent.23 It has
been proposed as an additive to food to control the
metabolism of sugars in patients suffering from dia-
betes and obesity.24 Conduritols A and B and analogs
are able to modulate the release of insulin from isolated
pancreatic islets in the presence of varying concentra-
tion of glucose, in both a stimulatory and inhibitory
sense.25 Cyclophellitol ((1S,2R,3S,4R,5R,6R)-5-hydrox-
The polyhydroxylated cycloheptanes 19–22 and
cyclooctanes 27–30 were assayed for their inhibitory
activities towards 25 commercially available glycosi-
dases. At 1 mM concentration (optimal pH, 35°C), they
were found to be inactive toward a-fucosidase from
human placenta, a-galactosidase from coffee beans and
ymethyl-7-oxa-bicyclo-[4.1.0]-heptane-2,3,4-triol) is
a
weak inhibitor of fungal b-xylosidase and a strong

Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
2557
Figure 2. X-Ray structure of 31 (for reasons of commodity atom numbering does not follow IUPAC numbering rules).
from A. niger, b-galactosidase from E. coli, amyloglu-
cosidases from A. niger and from Rhizopus mold, a-
mannosidases from jack beans and from almonds,
b-mannosidase from Helix pomatia, a-N-acetylgalac-
tosaminidase from chicken liver and b-N-acetylgalac-
tosaminidases from jack beans and from bovine
epididymis A and B. Weak inhibitory activities were
found for some of the compounds toward some glycosi-
dases (Tables 2 and 3). In general, the cyclohepta-
1,2,3,4,5-pentols were more active than the
cycloocta-1,2,3,4,5-pentols. The presence of five con-
tiguous hydroxy groups and a hydroxymethyl sub-
stituent is necessary for the inhibitory activity, as we
found that (1R,2S,3S,4R)-cycloocta-1,2,3,4-tetrol 326b
is completely inactive toward the 25 glycosidases
assayed in this study.
ranose might also be attributed to a conformational
factor (conjugation of seven-membered ring flexibility
and gauche interactions between the substituents). It is
interesting to note that 22, the 1-epimer of 20, is
recognized by some galactosidases and only weakly by
isomaltase from Baker’s yeast (Table 2). The most
striking outcome of this study is that carbasugar
analogs that do not possess an amine or an electrophilic
moiety (allylic alcohol, epoxide) can be moderate gly-
cosidase inhibitors.
3. Conclusion
Eight new polyhydroxylated carbocycles have been pre-
pared in six steps starting from commercially readily
available 2,3,5-tri-O-benzyl-D-arabinose. The ring-clos-
ing metathesis key step proceeded smoothly in the case
of cycloheptane derivatives but required the protection
of the tertiary alcohol in the case of cyclooctane com-
pounds. Further elaboration of the CꢁC bond and
subsequent deprotection afforded the target compounds
which showed some activity as glycosidase inhibitors
despite the lack of nitrogen in the compounds. Further
modifications of these compounds to improve their
potency against glycosidases, such as introduction of
nitrogen and/or deoxygenation of the tertiary alcohol
are underway and will be reported in due course.
The presence of a tertiary alcohol moiety at the posi-
tion corresponding to C-5 of pyranosides might be
responsible for the lack of activity. The geometry of the
cyclooctapentols 27–30 departs from that of
pyranosides more than the corresponding cyclohep-
tapentols 19–22. Although the high flexibility of seven-
membered rings might introduce an entropic penalty,
this factor could explain that the latter are better
recognized by glycosidases than the former carbasugar
4. Experimental
4.1. General methods
analogs. The fact that 20 with the b-
configuration is recognized by glucosidases and not its
diepimer 19 that has the configuration of a- -glucopy-
D
-mannopyranose
Melting points were determined using a Bu¨chi model
535 mp apparatus and are uncorrected. Optical rota-
tions were measured at 20 2°C with a Perkin–Elmer
D

2558
Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
Table 2. Inhibitory activities of cycloheptapentols 19–22. Percentage of inhibition at 1 mM concentration of the inhibitor.
Optimal pH, 35°Ca (NI=no inhibition)
model 241 digital polarimeter, using a 10 cm, 1 mL cell.
Chemical ionisation mass spectra (CI-MS ammonia)
and fast atom bombardment mass spectra (FAB-MS)
were obtained with a JMS-700 spectrometer. Elemental
analyses were performed by Service de Microanalyse de
l’Universite´ Pierre et Marie Curie, 4 Place Jussieu,
Note: for the assignment of the NMR spectra, the
numbering of the compounds is based on the analogy
with the corresponding sugar as shown for compounds
19 and 27 in Tables 2 and 3 and not on the IUPAC
rules for commodity reasons.
1
75005 Paris, France. H NMR spectra were recorded
4.2. (3R,4S,5R)-3,4-Dibenzyloxy-5-(benzyloxymethyl)-
nona-1,8-dien-5-ol 4a and (3R,4S,5S)-3,4-dibenzyloxy-5-
(benzyloxymethyl)nona-1,8-dien-5-ol, 4b
with a Bruker AC 250 or a Bruker DRX 400 or a
Bruker Avance 600 spectrometer for solutions in CDCl3
or CD3OD or D2O at ambient temperature. Assign-
ments were aided by COSY experiments. 13C NMR
spectra were recorded at 62.9 MHz with a Bruker AC
250 or at 100.6 MHz with a Bruker DRX 400 or at
150.9 MHz with a Bruker DRX 600 spectrometer for
solutions in CDCl3 adopting 77.00 ppm for the central
line of CDCl3. Assignments were aided by J-mod tech-
nique and proton–carbon correlation. Reactions were
monitored by thin-layer chromatography (TLC) on a
pre-coated plate of silica gel 60 F254 (layer thickness 0.2
mm; E. Merck, Darmstadt, Germany) and detection by
charring with sulfuric acid. Flash column chromatogra-
phy was performed on silica gel 60 (230–400 mesh, E.
Merck).
To a freshly prepared solution of butenylmagnesium
bromide (0.3 M in dry Et2O, 50 mL) was added drop-
wise under argon a solution of ketone 3 (3.75 g, 10.8
mmol) in anhydrous Et2O (60 mL). The reaction mix-
ture was stirred for 18 h at rt and quenched at 0°C by
dropwise addition of a sat. aq. NH4Cl solution (50
mL). The aqueous layer was extracted with AcOEt
(3×50 mL). Organic extracts were combined, dried
(MgSO4), filtered and the solvent was evaporated.
Purification by flash chromatography (AcOEt/cyclohex-
ane, 1:8) afforded dienes 4a and 4b (3.26 g, 6.9 mmol,
64% yield) as an inseparable mixture of diastereomers.

Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
2559
Table 3. Inhibitory activities of cyclooctapentols 27–30. Percentage of inhibition at 1 mM concentration of the inhibitor. Optimal
pH, 35°Ca (NI=no inhibition)b
1H NMR (CDCl3, 400 MHz): 7.39–7.30 (m, 30H, aro-
matic H), 6.05 (m, 2H, H-2a, H-2b), 5.78 (m, 1H, H-9a,
H-9b), 5.30–5.37 (m, 4H, H-1a, H-1b, H-1%a, H-1%b),
4.99 (m, 2H, H-10a, H-10b), 4.93 (m, 2H, H-10%a,
H-10%b), 4.23–4.82 (m, 12H, 6×CH2Ph), 4.21 (dd, 1H,
J=3.1 Hz, 8.1 Hz, H-3a), 4.13 (dd, 1H, J=3.4 Hz, 8.0
Hz, H-3b), 3.69 (s, 1H, OH), 3.62 (d, 2H, J=3.3 Hz,
H-4a, H-4b), 3.58 (d, 1H, J=9.0 Hz, H-6a), 3.56 (d,
1H, J=9.3 Hz, H-6b), 3.53 (s, 1H, OH), 3.35 (d, 1H,
J=9.0 Hz, H-6%a), 3.26 (d, 1H, J=9.3 Hz, H-6%b),
1.95–2.30 (m, 4H, H-8a, H-8b, H-8%a, H-8%b), 1.75 (m,
2H, H-7a, H-7%a), 1.62 (m, 1H, H-7b), 1.43 (m, 1H,
H-7%b); 13C NMR (CDCl3, 100 MHz): 139.20, 139.18
(C-9a, C-9b), 138.45, 138.26, 138.02, 137.98, 137.44,
137.22 (6×Cipso), 136.30, 136.07 (C-2a, C-2b), 127.59–
128.63 (aromatic C), 118.99, 118.47 (C-1a, C-1b),
114.07, 114.01 (C-10a, C-10b), 83.41, 82.54 (C-4a, C-
4b), 80.98, 80.90 (C-3a, C-3b), 76.53, 76.30 (C-5a,
C-5b), 76.14, 76.00 (2×CH2Ph), 73.25, 73.13 (2×
CH2Ph), 72.45, 70.72 (C-6a, C-6b), 70.11, 69.96 (2×
CH2Ph), 34.26, 33.77 (C-7a, C-7b), 27.22 (C-8a, C-8b);
filtered and the solvent was evaporated. Purification by
flash chromatography (AcOEt/cyclohexane, 1:10)
afforded diene 5a and 5b (3.69 g, 7.6 mmol, 70% yield),
as an inseparable mixture of diastereomers.
1H NMR (CDCl3, 400 MHz): 7.30–7.39 (m, 30H, aro-
matic H), 6.05 (m, 2H, H-2a, H-2b), 5.80 (m, 1H,
H-10a, H-10b), 5.29–5.38 (m, 4H, H-1a, H-1b, H-1%a,
H-1%b), 4.93–5.04 (m, 4H, H-10a, H-10b, H-10%a, H-
10%b), 4.23–4.82 (m, 12H, 6×CH2Ph), 4.21 (dd, 1H,
J=3.1 Hz, 8.1 Hz, H-3a), 4.12 (dd, 1H, J=3.5 Hz, 8.1
Hz, H-3b), 3.64 (s, 1H, OH), 3.61 (d, 2H, J=3.4 Hz,
H-4a, H-4b), 3.57 (d, 2H, J=8.8 Hz, H-6a, H-6b), 3.49
(s, 1H, OH), 3.37 (d, 1H, J=9.0 Hz, H-6%a), 3.27 (d,
1H, J=9.3 Hz, H-6%b), 1.93–2.03 (m, 4H, H-9a, H-9b,
H-9%a, H-9%b), 1.30–1.70 (m, 8H, H-7a, H-7%a, H-7b,
H-7%b, H-8a, H-8%a, H-8b, H-8%b); 13C NMR (CDCl3,
100 MHz): 138.90, 138.87 (C-10a, C-10b), 138.50,
138.30, 138.06, 138.03, 137.49, 137.31 (6×Cipso), 136.37,
136.13 (C-2a, C-2b), 127.47–128.65 (aromatic C),
118.89, 118.38 (C-1a, C-1b), 114.20, 114.03 (C-11a,
C-11b), 83.45, 82.60 (C-4a, C-4b), 81.06, 80.91 (C-3a,
C-3b), 76.67, 76.44 (C-5a, C-5b), 76.13, 75.96 (2×
CH2Ph), 73.25, 73.14 (2×CH2Ph), 72.61, 70.93 (C-6a,
C-6b), 70.10, 69.95 (2×CH2Ph), 34.50, 34.29, 34.21,
34.08 (C-7a, C-7b, C-9a, C-9b), 22.12, 22.03 (C-8a,
+
m/z (CI, NH3): 504 (M+NH4 , 100%). Anal. calcd for
C31H36O4: C, 78.78; H, 7.68. Found: C, 78.63; H,
7.79%.
4.3. (3R,4S,5R)-3,4-Dibenzyloxy-5-(benzyloxymethyl)-
deca-1,9-dien-5-ol 5a and (3R,4S,5S)-3,4-dibenzyloxy-5-
(benzyloxymethyl)deca-1,9-dien-5-ol 5b
+
C-8b); m/z (CI, NH3): 504 (M+NH4 , 100%). Anal.
calcd for C32H38O4: C, 78.97; H, 7.87. Found: C, 78.57;
H, 8.01%.
To a freshly prepared solution of pentenylmagnesium
bromide (0.3 M in Et2O, 50 mL) was added dropwise
under argon at 0°C a solution of ketone 3 (4.5 g, 10.8
mmol) in Et2O (80 mL). The reaction mixture was
stirred for 18 h at rt and quenched at 0°C by dropwise
addition of a sat. aq. NH4Cl solution (50 mL). The
aqueous layer was extracted with AcOEt (3×50 mL).
Organic extracts were combined, dried (MgSO4),
4.4. (1R,2S,3R)-2,3-Dibenzyloxy-1-(benzyloxymethyl)-
cyclohept-4-en-1-ol, 8 and (1S,2S,3R)-2,3-dibenzyloxy-1-
(benzyloxymethyl)cyclohept-4-en-1-ol, 9
Dienes 4a and 4b (100 mg, 0.212 mmol) were dissolved
in dry CH2Cl2 (50 mL) under argon. The solution was
degased for 10 min by bubbling argon through the

2560
Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
solution. Catalyst 7 (9 mg, 0.011 mmol, 5% mol) was
added and the solution was stirred at rt under argon.
After 24 h, some more catalyst 7 was added (9 mg,
0.011 mmol, 5% mol). After 45 h, the reaction was
quenched by stirring the reaction mixture with
Pb(OAc)4 (20 mg, 0.033 mmol) for 5 h. The solvent was
then evaporated and the residue purified by flash chro-
matography (EtOAc/cyclohexane, 1:20) to afford cyclo-
heptene 8 (47 mg, 0.106 mmol, 48% yield) as a colorless
oil.
colorless oil; [h]D=+2 (c 0.2 in CHCl3); 1H NMR
(CDCl3, 400 MHz): 7.39–7.27 (m, 15H, aromatic H),
5.77 (m, 1H, H-2), 5.71 (m, 1H, H-1), 5.11 (d, 1H,
J=10.5 Hz, CHPh), 4.73 (d, 1H, J=11.5 Hz, CHPh),
4.53–4.61 (m, 5H, H-3, 2×CH2Ph), 3.74 (d, 1H, J=9.8
Hz, H-4), 3.64 (d, 1H, J=8.3 Hz, H-6), 3.33 (d, 1H,
J=8.3 Hz, H-6%), 2.73 (s, 1H, OH), 2.35 (m, 1H, H-9),
2.17 (m, 1H, H-9%), 1.90 (m, 3H, H-7, H-7%, H-8), 1.43
(m, 1H, H-8%); 13C NMR (CDCl3, 100 MHz): 138.77,
138.55, 138.12 (3×Cipso), 132.49 (C-2), 131.01 (C-1),
127.31–128.44 (aromatic C), 82.90 (C-4), 77.51 (C-6),
77.47 (C-3), 75.78 (CH2Ph), 74.88 (C-5), 73.32
(CH2Ph), 71.66 (CH2Ph), 31.00 (C-9), 26.57 (C-8),
[h]D=+17 (c 1 in CHCl3); 1H NMR (CDCl3, 400
MHz): 7.27–7.39 (m, 15H, aromatic H), 5.93 (m, 1H,
H-1), 5.80 (m, 1H, H-2), 5.05 (d, 1H, J=10.7 Hz,
CHPh), 4.75 (s, 2H, CH2Ph), 4.63 (m, 1H, H-3), 4.55
(d, 1H, J=12.0 Hz, CHPh), 4.53 (d, 1H, J=10.7 Hz,
CHPh), 4.48 (1H, J=12.0 Hz, CHPh), 3.72 (d, 1H,
J=9.6 Hz, H-4), 3.62 (d, 1H, J=8.7 Hz, H-6), 3.28 (d,
1H, J=8.7 Hz, H-6%), 2.80 (s, 1H, OH), 2.37 (m, 1H,
H-8), 2.10 (m, 1H, H-8%), 2.01 (m, 1H, H-7), 1.78 (m,
1H, H-7%); 13C NMR (CDCl3, 100 MHz): 138.77,
138.38, 138.12 (3×Cipso), 132.95 (C-2), 132.00 (C-1),
127.34–128.32 (aromatic C), 80.87 (C-4), 77.31 (C-3),
76.33 (CH2Ph), 75.54 (C-6), 75.40 (C-5), 73.28
(CH2Ph), 73.03 (CH2Ph), 34.06 (C-7), 22.11 (C-8); m/z
+
21.94 (C-7); m/z (CI, NH3): 462 (M+NH4 , 100%).
Anal. calcd for C30H34O4: C, 78.57; H, 7.47. Found: C,
78.50; H, 7.79%.
Further elution afforded cyclooctene 11 (14 mg, 0.031
mmol, 15% yield) as a colorless oil; [h]D=−50 (c 0.1 in
CHCl3); 1H NMR (CDCl3, 400 MHz) 7.40–7.27 (m,
15H, aromatic H), 6.11 (ddd, 1H, J=4.5 Hz, 7.4 Hz,
11.7 Hz, H-1), 5.73 (ddd, 1H, J=2.3 Hz, 5.2 Hz, 11.5
Hz, H-2), 4.73 (d, 1H, J=11.6 Hz, CHPh), 4.65 (m,
4H, 2×CH2Ph), 4.52 (d, 1H, J=11.6 Hz, CHPh), 4.27
(dd, 1H, J=5.6 Hz, 6.8 Hz, H-3), 4.11 (s, 1H, OH),
3.98 (d, 1H, J=6.8 Hz, H-4), 3.65 (d, 1H, J=9.6 Hz,
H-6), 3.43 (d, 1H, J=9.6 Hz, H-6%), 2.53 (m, 1H, H-8),
2.11 (m, 1H, H-8%), 1.87 (ddd, 1H, H-7), 1.58 (ddd, 1H,
H-7%); 13C NMR (CDCl3, 100 MHz): 138.62, 138.42,
137.73 (3×Cipso), 135.94 (C-1), 128.13 (C-2), 127.45–
128.39 (aromatic C), 79.74 (C-4), 77.42 (C-5), 76.36
(C-3), 75.03 (C-6), 73.95, 73.58, 71.68 (3×CH2Ph), 31.70
+
(CI, NH3): 462 (M+NH4 , 100%); HRMS (CI, NH3)
calcd for C29H33O4 (MH+): 445.2379. Found: 445.2373.
Further elution afforded cycloheptene 9 (47 mg, 0.106
mmol, 49% yield) as a colorless oil; [h]D=−50 (c 0.1 in
CHCl3); 1H NMR (CDCl3, 400 MHz) 7.27–7.40 (m,
15H, aromatic H), 6.11 (ddd, 1H, J=4.5 Hz, 7.4 Hz,
11.7 Hz, H-1), 5.73 (ddd, 1H, J=2.3 Hz, 5.2 Hz, 11.5
Hz, H-2), 4.73 (d, 1H, J=11.6 Hz, CHPh), 4.65 (m,
4H, 2×CH2Ph), 4.52 (d, 1H, J=11.6 Hz, CHPh), 4.27
(dd, 1H, J=5.6 Hz, 6.8 Hz, H-3), 4.11 (s, 1H, OH),
3.98 (d, 1H, J=6.8 Hz, H-4), 3.65 (d, 1H, J=9.6 Hz,
H-6), 3.43 (d, 1H, J=9.6 Hz, H-6%), 2.53 (m, 1H, H-8),
2.11 (m, 1H, H-8%), 1.87 (ddd, 1H, H-7), 1.58 (ddd, 1H,
H-7%); 13C NMR (CDCl3, 100 MHz): 138.62, 138.42,
137.73 (3×Cipso), 135.94 (C-1), 128.13 (C-2), 127.45–
128.39 (aromatic C), 79.74 (C-4), 77.42 (C-5), 76.36
(C-3), 75.03 (C-6), 73.95, 73.58, 71.68 (3×CH2Ph), 31.70
+
(C-7), 22.18 (C-8); m/z (CI, NH3): 462 (M+NH4 ,
100%). Anal. calcd for C30H34O4: C, 78.57; H, 7.47.
Found: C, 78.16; H, 7.37%.
4.6. (3R,4S,5R)-3,4-Dibenzyloxy-5-(benzyloxymethyl)-5-
[(tert-butyl)dimethylsilyloxy]deca-1,9-diene, 12a and
(3R,4S,5S)-3,4-dibenzyloxy-5-(benzyloxymethyl)-5-
[(tert-butyl)dimethylsilyloxy]-deca-1,9-diene, 12b
To a solution of dienes 5a and 5b (500 mg, 1.03 mmol),
triethylamine (360 mL, 2.57 mmol) in CH2Cl2 (10 mL)
was added dropwise TBDMSOTf (435 mg, 1.65 mmol)
under argon at 0°C. The reaction mixture was stirred
for 18 h at rt. The solvent was evaporated and the
residue partitioned between dichloromethane and
water. Organic extracts was dried (MgSO4), filtered and
the solvent was evaporated. Purification by flash chro-
matography (AcOEt/cyclohexane, 1:30) afforded dienes
12a and 12b (552 mg, 0.926 mmol, 89% yield), as an
inseparable mixture of diastereomers. 1H NMR
(CDCl3, 400 MHz): 7.29–7.36 (m, 30H, aromatic H),
6.02 (m, 2H, H-2a, H-2b), 5.79 (m, 1H, H-10a, H-10b),
5.29 (m, 4H, H-1a, H-1b, H-1%a, H-1%b), 4.97 (m, 4H,
H-11a, H-11b, H-11%a, H-11%b), 4.33–4.80 (m, 12H,
6×CH2Ph), 4.25 (dd, 1H, J=3.1 Hz, 8.1 Hz, H-3a), 4.22
(dd, 1H, J=3.5 Hz, 8.1 Hz, H-3b), 3.74 (d, 1H, H-6b),
3.73 (d, 1H, H-4b), 3.62 (d, 1H, H-6a), 3.61 (d, 1H,
H-6%b), 3.56 (d, 1H, H-4a), 3.51 (d, 1H, H-6%a), 1.76–
2.05 (m, 4H, H-9a, H-9b, H-9%a, H-9%b), 1.36–1.61 (m,
8H, H-7a, H-7%a, H-7b, H-7%b, H-8a, H-8%a, H-8b,
H-8%b); 0.88, 0.87 (2×s, tBu a, tBu b); 0.09 (s, CH3Si b),
+
(C-7), 22.18 (C-8); m/z (CI, NH3): 462 (M+NH4 ,
100%). Anal. calcd for C29H32O4: C, 78.35; H, 7.25.
Found: C, 78.16; H, 7.37%.
4.5. (1R,2S,3R)-2,3-Dibenzyloxy-1-(benzyloxymethyl)-
cyclooct-4-en-1-ol, 10 and (1S,2S,3R)-2,3-dibenzyloxy-
1-(benzyloxymethyl)cyclooct-4-en-1-ol, 11
The diene 5a or 5b (100 mg, 0.212 mmol) was dissolved
in dry CH2Cl2 (50 mL) under argon. The solution was
degased for 10 min by bubbling argon through the
solution. Grubbs’ catalyst 6 (9 mg, 0.011 mmol, 5%
mol) was added and the solution was stirred at rt under
argon. After 24 h, some more catalyst 6 was added (9
mg, 0.011 mmol, 5% mol). After 72 h, the reaction was
quenched by stirring the reaction mixture with
Pb(OAc)4 (20 mg, 0.033 mmol) for 5 h. The solvent was
then evaporated and the residue purified by flash chro-
matography (EtOAc/cyclohexane, 1:20) to afford
cyclooctene 10 (13 mg, 0.029 mmol, 14% yield) as a

Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
2561
0.08 (s, CH3Si a), 0.06 (s, CH3Si b), −0.02 (s, CH3Si a);
13C NMR (CDCl3, 100 MHz): 139.09 (C-10a), 139.02
(C-10b), 138.47 (C-2a), 138.28, 138.26, 137.94 (Cipso),
138.15 (C-2b), 127.09–128.40 (aromatic C), 117.11 (C-
1a), 116.92 (C-1b), 114.27 (C-11b), 114.26 (C-11a), 85.27
(C-4a), 84.54 (C-4b), 80.47 (C-5a), 80.22 (C-5b), 79.11
(C-3b), 79.02 (C-3a), 75.41, 75.28 (2×CH2Ph), 73.88
(C-6a), 73.39 (C-6b), 73.02, 72.92, 70.18, 70.13 (4×
CH2Ph), 34.51, 34.49, 34.31, 33.59 (C-7a, C-7b, C-9a,
C-9b), 26.31, 26.28 (tBu a, tBu b), 22.81, 22.57 (C-8a,
C-8b), −2.70, −2.84, −3.02 (4×CH3Si); m/z (CI, NH3):
13C NMR (CDCl3, 100 MHz): 139.20, 139.07, 138.27
(3×Cipso), 133.89 (C-1), 129.60 (C-2), 127.07–128.29 (aro-
matic C), 84.24 (C-4), 79.27 (C-5), 78.10 (C-6), 76.79
(C-3), 75.25 (CH2Ph), 72.87 (CH2Ph), 71.12 (CH2Ph),
33.27 (C-7), 27.95 (C-9), 26.52 (tBuSi), 24.59 (C-8),
+
−2.03, −2.27 (2×SiCH3); m/z (CI, NH3): 590 (M+NH4 ,
100%).
4.8. (1S,2S,3R,4S,5S)-2,3-Dibenzyloxy-1-(benzyloxy-
methyl)cyclohepta-1,5,6-triol, 15 and (1S,2S,3R,4R,5R)-
2,3-dibenzyloxy-1-(benzyloxymethyl)cyclohepta-
1,5,6-triol, 16
+
618 (M+NH4 , 100%); HRMS (CI, NH3) calcd for
+
C38H56O4NSi (M+NH4 ): 618.3979. Found: 618.3984.
4.7. (1R,2S,3R)-2,3-Dibenzyloxy-1-(benzyloxymethyl)-1-
[(tert-butyl)dimethylsilyloxy]-cyclooct-4-ene, 13 and
(1S,2S,3R)-2,3-dibenzyloxy-1-(benzyloxymethyl)-1-
[(tert-butyl)dimethylsilyloxy]-cyclooct-4-ene, 14
Cycloheptene 8 (227 mg, 0.51 mmol) was dissolved in
acetone/water (8/1, 9 mL). N-Methyl morpholine oxide
(151 mg, 1.12 mmol) was added, followed by OsO4 (10
mL, 2.5% wt in tBuOH). The reaction mixture was stirred
for 5 days at rt and OsO4 (10 mL, 2.5% wt in tBuOH)
was added every day. The reaction mixture was then
diluted with CH2Cl2 (10 mL) and H2O (10 mL). The
aqueous layer was extracted with CH2Cl2 (10 mL) and
the organic extracts were combined, dried (MgSO4) and
the solvent removed under reduced pressure. Purification
by careful flash chromatography (EtOAc/cyclohexane,
1:4) afforded triol 15 as a colorless oil (60 mg, 0.125
mmol, 25% yield); [h]D=+21 (c 0.1 in CHCl3); 1H NMR
(CDCl3, 400 MHz): 7.38–7.24 (m, 15H, aromatic H), 4.76
(d, 1H, J=11.3 Hz, CHPh), 4.72 (d, 1H, J=11.8 Hz,
CHPh), 4.57 (d, 1H, J=11.8 Hz, CHPh), 4.52 (d, 1H,
J=12.0 Hz, CHPh), 4.46 (d, 1H, J=12.0 Hz, CHPh),
4.45 (d, 1H, J=11.3 Hz, CHPh), 4.09 (m, 1H, H-2), 3.96
(m, 2H, H-3, H-4), 3.91 (m, 1H, H-1), 3.38 (d, 1H, J=8.7
Hz, H-6), 3.24 (d, 1H, J=8.7 Hz, H-6%), 3.22 (d, 1H,
J=9.7 Hz, OH-1), 3.07 (s, 1H, OH-5), 2.94 (d, 1H, J=6.6
Hz, OH-2), 2.19 (m, 1H, H-7), 2.04 (m, 2H, H-8), 1.80
(m, 1H, H-8%), 1.52 (m, 1H, H-7%); 13C NMR (CDCl3, 100
MHz): 138.11, 137.49, 137.44 (3×Cipso), 127.67–128.82
(aromatic C), 83.56 (C-2), 77.22 (C-5), 75.92 (C-1), 74.16
(CH2Ph), 74.16 (CH2Ph), 73.79 (C-6), 73.44 (C-3), 73.33
(CH2Ph), 71.36 (C-4), 29.68 (C-7), 28.12 (C-8); m/z (CI,
Dienes 12a and 12b (250 mg, 0.417 mmol) were dissolved
in dry toluene (85 mL) under argon. The solution was
degased for 10 min by bubbling argon through the
solution. Grubbs’ catalyst 6 (17 mg, 0.021 mmol, 5% mol)
was added dropwise with a syringe pump over 10 h as
a solution in dry toluene and the solution was stirred at
rt under argon. After 24 h, some more catalyst 6 was
added (17 mg, 0.021 mmol, 5% mol). After 72 h, the
reaction was quenched by stirring the reaction mixture
with Pb(OAc)4 (23 mg, 0.11 mmol) for 4 h. The solvent
was then evaporated and the residue purified by flash
chromatography (EtOAc/cyclohexane, 1:200) to afford
cyclooctenes 13 and 14 (207 mg, 0.36 mmol, 86% yield)
as an inseparable mixture of diastereomers.
Spectroscopic data for 13: 1H NMR (CDCl3, 400 MHz):
7.34–7.26 (m, 15H, aromatic H), 5.90 (m, 1H, H-1), 5.66
(m, 1H, H-2), 5.11 (d, 1H, J=11.3 Hz, CHPh), 4.77 (d,
1H, J=11.3 Hz, CHPh), 4.63 (d, 1H, J=11.6 Hz,
CHPh), 4.49 (m, 1H, H-3), 4.47 (d, 1H, J=11.6 Hz,
CHPh), 4.40 (s, 2H, CH2Ph), 3.82 (d, 1H, J=8.8 Hz,
H-4), 3.71 (d, 1H, J=9.2 Hz, H-6), 3.35 (d, 1H, J=9.2
Hz, H-6%), 2.22 (m, 1H, H-9), 2.12 (m, 1H, H-9%), 1.81
(m, 1H, H-8), 1.65 (m, 2H, H-7, H-7%), 1.55 (m, 1H, H-8%),
1.30 (s, 9H, tBu), 0.12 (s, 6H, Si(CH3)2); 13C NMR
(CDCl3, 100 MHz): 139.98, 138.80, 137.74 (3×Cipso),
132.33 (C-1), 131.41 (C-2), 126.87–128.24 (aromatic C),
86.77 (C-4), 81.48 (C-3), 79.15 (C-5), 77.00 (C-6), 75.81
(CH2Ph), 73.22 (CH2Ph), 71.89 (CH2Ph), 31.78 (C-7),
26.26 (C-9), 26.11 (tBuSi), 22.22 (C-8), −2.12, −2.21
+
NH3): 496 (M+NH4 , 100%); HRMS (CI, NH3) calcd for
+
C29H38O6N (M+NH4 ): 496.2699. Found: 496.2701.
Further elution afforded triol 16 (140 mg, 0.293 mmol,
57% yield) as a colorless oil; [h]D=+41 (c 0.22 in CHCl3);
1H NMR (CDCl3, 400 MHz): 7.39–7.22 (m, 15H, aro-
matic H), 4.90 (d, 1H, J=11.0 Hz, CHPh), 4.88 (d, 1H,
J=11.3 Hz, CHPh), 4.62 (d, 1H, J=11.3 Hz, CHPh),
4.52 (d, 1H, J=12.0 Hz, CHPh), 4.48 (d, 1H, J=11.0 Hz,
CHPh), 4.43 (d, 1H, J=12.0 Hz, CHPh), 4.08 (m, 1H,
H-1), 3.97 (app t, 1H, J=7.7 Hz, H-3), 3.74 (m, 1H, H-2),
3.66 (d, 1H, J=7.3 Hz, H-4), 3.64 (d, 1H, OH-2), 3.48
(d, 1H, J=8.4 Hz, H-6), 3.28 (d, 1H, J=8.4 Hz, H-6%),
3.06 (s, 1H, OH-5), 2.84 (br s, 1H, OH-1), 1.97 (m, 2H,
H-7, H-8), 1.85 (m, 2H, H-7%, H-8%); 13C NMR (CDCl3,
100 MHz): 137.86, 137.76, 137.66 (3×Cipso), 127.65–
128.58 (aromatic C), 82.05 (C-4), 78.23 (C-3), 76.15
(C-6), 75.10 (CH2Ph), 74.69 (CH2Ph), 74.36 (C-2), 73.73
(C-5), 73.30 (CH2Ph), 68.27 (C-1), 27.87, 27.35 (C-7,
+
(2×SiCH3); m/z (CI, NH3): 590 (M+NH4 , 100%). Anal.
calcd for C36H48O4Si: C, 75.48; H, 8.45. Found: C, 74.92;
H, 8.68%.
Spectroscopic data for 14: 1H NMR (CDCl3, 400 MHz):
7.39–7.30 (m, 15H, aromatic H), 5.81 (m, 1H, H-2), 5.64
(m, 1H, H-1), 5.12 (d, 1H, J=10.6 Hz, CHPh), 4.71 (d,
1H, J=11.5 Hz, CHPh), 4.61 (d, 1H, J=11.5 Hz,
CHPh), 4.57 (m, 1H, H-3), 4.49 (s, 2H, CH2Ph), 4.46 (d,
1H, J=10.6 Hz, CHPh), 3.83 (d, 1H, J=7.1 Hz, H-6),
3.53 (d, 1H, J=10.0 Hz, H-4), 3.15 (d, 1H, J=7.1 Hz,
H-6%), 2.38 (m, 1H, H-9), 2.10 (m, 1H, H-9%), 1.95 (m, 1H,
H-8), 1.82 (m, 2H, H-7, H-7%), 1.32 (m, 1H, H-8%), 0.91
(s, 9H, tBu), 0.10 (s, 3H, Si(CH3)), 0.04 (s, 3H, Si(CH3));
+
C-8); m/z (CI, NH3): 496 (M+NH4 , 100%). Anal. calcd
for C29H34O6: C, 72.78; H, 7.16. Found: C, 73.10; H,
7.54%.

2562
Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
4.9. (1R,2S,3R,4S,5S)-2,3-Dibenzyloxy-1-(benzyloxy-
methyl)cyclohepta-1,5,6-triol, 17 and (1R,2S,3R,4R,5R)-
2,3-dibenzyloxy-1-(benzyloxymethyl)cyclohepta-1,5,6-
triol, 18
through Celite, eluted with MeOH. The solvent was
removed under reduced pressure to afford pentol 19 as
a colorless oil (29 mg, 0. 140 mmol, quant. yield);
[h]D=+11 (c 0.35 in CH3OH); 1H NMR (D2O, 400
MHz): 3.98 (m, 1H, H-1), 3.81 (app t, 1H, J=7.8 Hz,
H-3), 3.64 (dd, 1H, J=3.0 Hz, 7.6 Hz, H-2), 3.59 (d, 1H,
J=11.3 Hz, H-6), 3.50 (d, 1H, J=11.3 Hz, H-6%), 3.47
(d, 1H, J=8.3 Hz, H-4), 1.67–1.87 (m, 4H, H-7, H-7%,
H-8, H-8%); 13C NMR (D2O, 100 MHz): 75.76 (C-2),
75.02 (C-5), 74.80 (C-4), 72.00 (C-3), 70.02 (C-1), 66.92
(C-6), 28.28, 24.88 (C-7, C-8); m/z (ES+): 231 (M+Na+,
100%), 247 (M+K+, 5%).
Cycloheptene 9 (289 mg, 0.65 mmol) was dissolved in
acetone/water (8/1, 9 mL). N-Methyl morpholine oxide
(193 mg, 1.43 mmol) was added followed by OsO4 (10
mL, 2.5% wt in tBuOH). The reaction mixture was stirred
for 6 days at rt and OsO4 (10 mL, 2.5% wt in tBuOH)
was added every day. The reaction mixture was then
diluted with CH2Cl2 (10 mL) and H2O (10 mL). The
aqueous layer was extracted with CH2Cl2 (10 mL) and
the organic extracts were combined, dried (MgSO4) and
the solvent removed under reduced pressure. Purification
by careful flash chromatography (EtOAc/cyclohexane,
1:3) afforded triol 17 as a colorless oil (208 mg, 0.435
4.11. (1S,2S,3R,4R,5R)-1-(Hydroxymethyl)cyclohepta-
1,2,3,4,5-pentol, 20
Triol 16 was deprotected as described for 19 to afford
1
1
mmol, 67% yield); [h]D=+38.5 (c 0.93 in CHCl3); H
compound 20; [h]D=+20 (c 0.60 in CH3OH); H NMR
NMR (CDCl3, 400 MHz): 7.39–7.22 (m, 15H, aromatic
H), 4.81 (d, 1H, J=11.6 Hz, CHPh), 4.69 (d, 1H, J=11.6
Hz, CHPh), 4.62 (d, 1H, J=11.2 Hz, CHPh), 4.56 (d, 1H,
J=11.9 Hz, CHPh), 4.42 (d, 1H, J=11.9 Hz, CHPh),
4.30 (d, 1H, J=11.2 Hz, CHPh), 4.13 (ddd, 1H, J=1.7
Hz, 5.4 Hz, H-2), 4.06 (m, 1H, H-1), 3.95 (d, 1H, J=3.1
Hz, H-4), 3.87 (dd, 1H, J=3.1 Hz, 7.1 Hz, H-3), 3.46 (d,
1H, J=9.1 Hz, H-6), 3.43 (d, 1H, J=7.9 Hz, OH-1), 3.26
(d, 1H, J=9.1 Hz, H-6%), 2.89 (d, 1H, J=0.6 Hz, OH-5),
2.79 (d, 1H, J=5.3 Hz, OH-2), 1.97–2.03 (m, 2H, H-7,
H-7%), 1.87 (m, 1H, H-8), 1.41 (1H, m, H-8%); 13C NMR
(CDCl3, 100 MHz): 137.84, 137.79, 136.72 (3×Cipso),
127.68–128.52 (aromatic C), 82.96 (C-3), 79.33 (C-4),
78.52 (C-2), 75.50 (C-5), 75.20 (C-6), 73.36 (CH2Ph),
73.35 (CH2Ph), 73.18 (C-1), 73.12 (CH2Ph), 26.79 (C-8),
(D2O, 400 MHz): 4.11 (m, 1H, H-2), 3.83 (ddd, 1H,
J=2.9 Hz, 5.0 Hz, 9.9 Hz, H-1), 3.75 (m, 2H, H-3, H-4),
3.56 (d, 1H, J=11.5 Hz, H-6), 3.51 (d, 1H, J=11.5 Hz,
H-6%), 2.05 (ddd, 1H, J=3.4 Hz, 9.6 Hz, 15.1 Hz, H-7),
1.64 (2H, m, H-8, H-8%), 1.43 (ddd, 1H,, J=3.5 Hz, 8.1
Hz, 15.1 Hz, H-7%); 13C NMR (D2O, 100 MHz): 75.41
(C-2), 74.82 (C-5), 72.03 (C-4), 69.88 (C-3), 69.20 (C-1),
66.90 (C-6), 28.71, 24.99 (C-7, C-8); m/z (ES+): 231
(M+Na+, 100%), 247 (M+K+, 5%).
4.12. (1R,2S,3R,4S,5S)-1-(Hydroxymethyl)cyclohepta-
1,2,3,4,5-pentol, 21
Triol 17 was deprotected as described for 19 to afford 21;
[h]D=+29 (c 0.79 in CH3OH); 1H NMR (D2O, 400
MHz): 4.07 (m, 1H, H-1), 3.81 (dd, 1H, J=2.2 Hz, 7.7
Hz, H-2), 3.76 (dd, 1H, J=5.4 Hz, 7.7 Hz, H-3), 3.64 (d,
1H, J=5.4 Hz, H-4), 3.59 (d, 1H, J=11.8 Hz, H-6), 3.47
(d, 1H, J=11.8 Hz, H-6%), 1.75–1.92 (3H, m, H-7, H-7%,
H-8), 1.43 (m, 1H, H-8); 13C NMR (D2O, 100 MHz):
77.22 (C-2), 76.24 (C-5, C-4), 75.04 (C-3), 71.86 (C-1),
66.71 (C-6), 25.86, 25.27 (C-7, C-8); m/z (ES+): 231
(M+Na+, 100%), 247 (M+K+, 5%).
+
24.87 (C-7); m/z (CI, NH3): 496 (M+NH4 , 100%). Anal.
calcd for C29H34O6: C, 72.78; H, 7.16. Found: C, 72.61;
H, 7.33%.
Further elution afforded triol 18 as a white solid (45 mg,
0.094 mmol, 15% yield); [h]D=+4 (c 1 in CHCl3); mp
1
99–100°C; H NMR (CDCl3, 400 MHz): 7.40–7.22 (m,
15H, aromatic H), 4.74 (d, 1H, J=11.5 Hz, CHPh), 4.64
(d, 1H, J=11.5 Hz, CHPh), 4.63 (d, 1H, J=11.3 Hz,
CHPh), 4.57 (d, 1H, J=11.9 Hz, CHPh), 4.52 (d, 1H,
J=11.9 Hz, CHPh), 4.47 (d, 1H, J=11.3 Hz, CHPh),
4.26 (m, 2H, H-2, OH), 3.91 (app d, 1H, J=4.3 Hz, H-4),
3.88 (app d, 1H, J=4.3 Hz, H-3), 3.82 (m, 1H, H-1), 3.65
(d, 1H, J=7.9 Hz, OH-1), 3.59 (d, 1H, J=9.1 Hz, H-6),
3.24 (d, 1H, J=9.1 Hz, H-6%), 2.42 (s, 1H, OH-5), 2.06
(m, 1H, H-8), 1.88 (m, 1H, H-8%), 1.75 (m, 1H, H-7), 1.51
(1H, m, H-7%); 13C NMR (CDCl3, 100 MHz): 138.05,
137.65, 137.61 (3×Cipso), 127.68–128.57 (aromatic C),
82.98 (C-3), 81.77 (C-4), 75.39 (C-6), 75.32 (C-5), 73.45
(CH2Ph), 73.39 (CH2Ph), 72.99 (C-2), 72.27 (CH2Ph),
71.84 (C-1), 26.74 (C-7), 26.03 (C-8); m/z (CI, NH3): 496
4.13. (1R,2S,3R,4R,5R)-1-(Hydroxymethyl)cyclohepta-
1,2,3,4,5-pentol, 22
Triol 18 was deprotected as described for 19 to afford 22;
[h]D=+16 (c 0.55 in CH3OH); 1H NMR (D2O, 400
MHz): 4.03 (m, 1H, H-2), 3.83 (ddd, 1H, J=2.4 Hz, 5.7
Hz, 12.3 Hz, H-1), 3.81 (d, 1H, H-4), 3.72 (dd, 1H, J=1.4
Hz, 7.8 Hz, H-3), 3.64 (d, 1H, J=11.8 Hz, H-6), 3.43 (d,
1H, J=11.8 Hz, H-6%), 1.72–1.88 (2H, m, H-8, H-8%),
1.57–1.61 (m, 2H, H-7, H-7%); 13C NMR (D2O, 100
MHz): 77.77 (C-2), 76.97 (C-1 or C-4), 75.12 (C-5), 74.57
(C-3), 72.18 (C-1 or C-4), 66.86 (C-6), 27.19 (C-7), 24.42
(C-8); m/z (ES+): 231 (M+Na+, 100%), 247 (M+K+, 5%).
+
(M+NH4 , 100%); HRMS (CI, NH3) calcd for C29H35O6
(MH+): 479.2434. Found: 479.2439.
4.14. (1S,2S,3R,4S,5S)-2,3-Dibenzyloxy-1-(benzyloxy-
methyl)cycloocta-1,4,5-triol, 23 and (1S,2S,3R,4R,5R)-
2,3-dibenzyloxy-1-(benzyloxymethyl)cycloocta-1,4,5-
triol, 24
4.10. (1S,2S,3R,4S,5S)-1-(Hydroxymethyl)cyclohepta-
1,2,3,4,5-pentol, 19
Triol 15 (67 mg, 0.140 mmol) was dissolved in EtOAc/
MeOH (1:1, 10 mL) and 10% Pd/C (10 mg) was added.
The suspension was stirred under H2 for 1 h, filtered
These products were synthesized as previously described
for 15 and 16.

Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
2563
Spectroscopic data for triol 23: [h]D=+32 (c 0.60 in
15H, aromatic H), 4.98 (d, 1H, J=11.6 Hz, CHPh),
4.86 (d, 1H, J=11.2 Hz, CHPh), 4.67 (d, 1H, J=11.2
Hz, CHPh), 4.66 (d, 1H, J=11.6 Hz, CHPh), 4.57 (s,
2H, CH2Ph), 4.28 (m, 1H, H-2), 4.25 (d, 1H, J=8.0 Hz,
H-4), 4.14 (dd, 1H, J=2.3 Hz, 8.0 Hz, H-3), 3.94 (m,
1H, H-1), 3.62 (d, 1H, J=8.9 Hz, H-6), 3.38 (d, 1H,
J=8.9 Hz, H-6%), 3.18 (d, 1H, J=7.3 Hz, OH-2), 2.83
(d, 1H, J=3.0 Hz, OH-1), 2.65 (s, 1H, OH-5), 2.16 (m,
2H, H-7, H-9), 1.93 (m, 1H, H-8), 1.76 (m, 2H, H-7%,
H-9%), 1.61 (m, 1H, H-8%); 13C NMR (CDCl3, 100
MHz): 138.50, 138.01, 137.84 (3×Cipso), 127.45–128.58
(aromatic C), 83.36 (C-4), 81.51 (C-3), 75.77 (C-5),
75.15 (CH2Ph), 75.12 (CH2Ph), 74.55 (C-6), 74.11 (C-
1), 73.47 (CH2Ph), 73.07 (C-2), 31.71 (C-7), 31.65 (C-9),
1
CHCl3); H NMR (CDCl3, 400 MHz): 7.39–7.30 (m,
15H, aromatic H), 5.00–4.89 (m, 2H, CH2Ph), 4.64–
4.46 (m, 4H, 2×CH2Ph), 4.08 (dd, 1H, J=7.2 Hz, 9.4
Hz, H-3), 4.02 (m, 1H, J=2.4 Hz, 10.8 Hz, H-1), 3.83
(dd, 1H, J=3.0 Hz, 9.4 Hz, H-2), 3.70 (d, 1H, J=7.2
Hz, H-4), 3.58 (d, 1H, J=8.5 Hz, H-6), 3.39 (d, 1H,
J=8.5 Hz, H-6%), 2.10–1.80 (m, 3H, H-9, H-9%, H-7),
1.70–1.42 (m, 3H, H-7%, H-8, H-8%); 13C NMR (CDCl3,
100 MHz): 138.21, 137.96, 137.74 (3×Cipso), 128.34–
127.51 (aromatic C), 78.04 (C-4), 77.05 (C-2), 76.86
(C-3), 74.92 (C-5), 74.67 (C-6), 74.52 (CH2Ph), 74.12
(CH2Ph), 73.38 (CH2Ph), 69.39 (C-1), 31.00 (C-7),
+
29.19 (C-9), 17.81 (C-8); m/z (CI, NH3): 510 (M+NH4 ,
+
100%). Anal. calcd for C30H36O6: C, 73.15; H, 7.37.
Found: C, 73.39; H, 7.82%.
17.60 (C-8); m/z (CI, NH3): 510 (M+NH4 , 100%);
+
HRMS (CI, NH3) calcd for C30H40O6N (MNH4 ):
510.2856. Found: 510.2858.
Spectroscopic data for triol 24: [h]D=+12 (c 0.75 in
1
CHCl3); H NMR (CDCl3, 400 MHz): 7.39–7.30 (m,
4.16. (1S,2S,3R,4S,5S)-1-(Hydroxymethyl)cycloocta-
1,2,3,4,5-pentol, 27
15H, aromatic H), 5.00–4.89 (m, 2H, CH2Ph), 4.64–
4.46 (m, 4H, 2×CH2Ph), 4.28 (m, 1H, H-2), 4.17 (d, 1H,
J=7.4 Hz, H-4), 3.91 (dd, 1H, J=1.6 Hz, 7.4 Hz, H-3),
3.69 (m, 1H, H-1), 3.49 (d, 1H, J=9.3 Hz, H-6), 3.38
(d, 1H, J=9.3 Hz, H-6%), 2.10–1.80 (m, 3H, H-9, H-9%,
H-7), 1.70–1.42 (m, 3H, H-7%, H-8, H-8%); 13C NMR
(CDCl3, 100 MHz): 138.41, 138.06, 138.05 (3×Cipso),
127.51–128.34 (aromatic C), 76.63 (C-3%), 76.03 (C-6),
75.36 (C-5), 75.27 (C-2), 75.17 (CH2Ph), 74.43 (C-4),
74.23 (CH2Ph), 73.38 (CH2Ph), 70.96 (C-1), 33.27 (C-
7), 28.31 (C-9), 20.15 (C-8); m/z (CI, NH3): 510 (M+
This compound was obtained as a foam using the
method previously described for 19; [h]D=−8 (c 0.55 in
CH3OH); 1H NMR (D2O, 400 MHz): 4.06 (dd, 1H,
J=7.4 Hz, 8.8 Hz, H-3), 3.91 (ddd, 1H, J=2.5 Hz, 2.8
Hz, 11.3 Hz, H-2), 3.75 (dd, 1H, J=2.5 Hz, 8.8 Hz,
H-2), 3.65 (d, 1H, J=11.3 Hz, H-6), 3.62 (d, 1H, J=7.4
Hz, H-4), 3.48 (d, 1H, J=11.3 Hz, H-6%), 1.85–1.48 (m,
6H, H-7, H-7%, H-8, H-8%, H-9, H-9%); 13C NMR (D2O,
100 MHz): 78.43 (C-2), 75.64 (C-5), 68.88 (C-1, C-4),
68.74 (C-3), 67.36 (C-6), 31.40 (C-7), 29.40 (C-9), 16.52
(C-8); m/z (ES+): 245 (M+Na+, 100%).
+
NH4 , 100%). Anal. calcd for C30H36O6: C, 73.15; H,
7.37. Found: C, 73.30; H, 7.70%.
4.15. (1R,2S,3R,4S,5S)-2,3-Dibenzyloxy-1-(benzyloxy-
methyl)cycloocta-1,4,5-triol, 25 and (1R,2S,3R,4R,5R)-
2,3-dibenzyloxy-1-(benzyloxymethyl)cycloocta-1,4,5-
triol, 26
4.17. (1S,2S,3R,4R,5R)-1-(Hydroxymethyl)cycloocta-
1,2,3,4,5-pentol, 28
This compound was obtained as a foam using the
method previously described for 19; [h]D=−2 (c 0.88 in
CH3OH); 1H NMR (D2O, 400 MHz): 4.12 (m, 1H,
H-2), 3.90 (m, 2H, H-3, H-4), 3.87 (m, 1H, H-1), 3.73
(dd, 1H, J=0.5 Hz, 12.0 Hz, H-6), 3.61 (d, 1H, J=12.0
Hz, H-6%), 1.97–1.83 (m, 2H, H-9, H-7), 1.72–1.61 (m,
1H, H-8), 1.52–1.34 (m, 3H, H-7%, H-8%, H-9%); 13C
NMR (D2O, 100 MHz): 76.70 (C-5), 75.79 (C-2), 70.67
(C-1), 67.34, 66.12 (C-3, C-4), 64.75 (C-6), 28.19 (C-7),
27.11 (C-9), 19.76 (C-8); m/z (ES+): 245 (M+Na+,
100%).
These products were synthesized as previously
described for 17 and 18.
Spectroscopic data for triol 25: [h]D=+37 (c 1 in
1
CHCl3); H NMR (CDCl3, 400 MHz): 7.38–7.30 (m,
15H, aromatic H), 4.83 (d, 1H, J=11.6 Hz, CHPh),
4.80 (d, 1H, J=11.0 Hz, CHPh), 4.57 (d, 1H, J=11.7
Hz, CHPh), 4.50 (d, 1H, J=11.0 Hz, CHPh), 4.49 (d,
1H, J=11.7 Hz, CHPh), 4.46 (m, 1H, H-2), 4.43 (d,
1H, J=11.6 Hz, CHPh), 4.09 (m, 1H, H-1), 4.05 (d,
1H, J=4.2 Hz, H-4), 3.95 (dd, 1H, J=8.7 Hz, 4.2 Hz,
H-3), 3.52 (d, 1H, J=8.9 Hz, H-6), 3.28 (d, 1H, J=8.9
Hz, H-6%), 3.12 (d, 1H, J=1.6 Hz, OH-2), 2.88 (s, 1H,
OH-5), 2.61 (d, 1H, J=3.0 Hz, OH-1), 2.01 (m, 2H,
H-9), 1.88 (m, 1H, H-7), 1.65 (m, 2H, H-8), 1.58 (m,
1H, H-7%); 13C NMR (CDCl3, 100 MHz): 137.98,
137.83, 137.48 (3×Cipso), 127.78–128.57 (aromatic C),
79.63 (C-3, C-4), 76.16 (C-6), 75.91 (C-5), 73.71
(CH2Ph), 73.58 (CH2Ph), 73.31 (CH2Ph), 72.79 (C-2),
71.25 (C-1), 33.14 (C-7, C-8), 29.20 (C-9); m/z (CI,
4.18. (1R,2S,3R,4S,5S)-1-(Hydroxymethyl)cycloocta-
1,2,3,4,5-pentol, 29
This compound was obtained as a foam using the
method previously described for 19; [h]D=−15 (c 0.30
1
in CH3OH); H NMR (D2O, 400 MHz): 3.97 (dd, 1H,
J=3.0 Hz, 10.3 Hz, H-1), 3.83 (dd, 1H, J=3.0 Hz, 7.3
Hz, H-2), 3.70 (dd, 1H, J=5.8 Hz, 7.3 Hz, H-3), 3.68
(d, 1H, J=5.8 Hz, H-4), 3.66 (d, 1H, J=11.9 Hz, H-6),
3.56 (d, 1H, J=11.9 Hz, H-6%), 1.84–1.52 (m, 6H, H-7,
H-7%, H-8, H-8%, H-9, H-9%); 13C NMR (D2O, 100
MHz): 76.81 (C-5), 76.62 (C-2), 72.46 (C-3), 71.31
(C-1), 70.39 (C-4), 64.19 (C-6), 33.31 (C-7), 31.21 (C-9),
18.35 (C-8); m/z (ES+): 245 (M+Na+, 100%).
+
NH3): 510 (M+NH4 , 100%); HRMS (CI, NH3) calcd
for C30H37O6 (MH+): 493.2590. Found: 493.2589.
Spectroscopic data for triol 26: [h]D=+11 (c 1 in
1
CHCl3); H NMR (CDCl3, 400 MHz): 7.38–7.30 (m,

2564
Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
4.19. (1R,2S,3R,4R,5R)-1-(Hydroxymethyl)cycloocta-
1,2,3,4,5-pentol, 30
References
1. (a) Martinez-Grau, A.; Marco-Contelles, J. Chem. Soc.
Rev. 1998, 27, 155 and references cited herein; (b) Dalko,
P. I.; Sinay¨, P. Angew. Chem., Int. Ed. 1999, 38, 773.
2. Ogawa, S. In Carbohydrates in Drug Design; Witczak, Z.
J.; Nieforth, K. A., Eds.; Dekker: New York, 1997; p.
433.
3. For example, see: (a) Ackermann, L.; El Tom, D.; Fu¨rst-
ner, A. Tetrahedron 2000, 56, 2195–2202; (b) Hyldtoft, L.;
Madsen, R. J. Am. Chem. Soc. 2000, 122, 8444–8452; (c)
Callam, C. S.; Lowary, T. L. Org. Lett. 2000, 2, 167–169.
4. (a) Marco-Contelles, J.; de Opazo, E. Tetrahedron Lett.
1999, 40, 4445–4448; (b) Marco-Contelles, J.; de Opazo,
E. J. Org. Chem. 2000, 65, 5416–5419; (c) Marco-Con-
telles, J.; de Opazo, E. Tetrahedron Lett. 2000, 41, 5341–
5345; (d) Marco-Contelles, J.; de Opazo, E. Tetrahedron
Lett. 2000, 41, 2439–2441; (e) Boyer, F.-D.; Hanna, I.
Tetrahedron Lett. 2001, 42, 1275–1277; (f) Marco-Con-
telles, J.; de Opazo, E. J. Org. Chem. 2002, 67, 3705–3717
and references cited therein.
5. (a) Hanna, I.; Ricard, L. Org. Lett. 2000, 2, 2651–2654;
(b) Boyer, F.-D.; Hanna, I.; Nolan, S. P. J. Org. Chem.
2001, 66, 4094–4096; (c) van Hooft, P. A. V.; van der
Marel, G. A.; van Boeckel, C. A. A.; van Boom, J. H.
Tetrahedron Lett. 2001, 42, 1769–1772; (d) van Hooft, P.
A.; Litjens, R. E. J. N.; van der Marel, G. A.; van
Boeckel, C. A. A.; van Boom, J. H. Org. Lett. 2001, 3,
731–733; (e) McNulty, J.; Grunner, V.; Mao, J. Tetra-
hedron Lett. 2001, 42, 5609–5612; (f) Gravier-Pelletier, C.;
Andriuzzi, O.; Le Merrer, Y. Tetrahedron Lett. 2002, 43,
245–248.
6. (a) Wang, W.; Zhang, Y.; Sollogoub, M.; Sinay¨, P.
Angew. Chem., Int. Ed. 2000, 39, 2466–2467; (b) Wang,
W.; Zhang, Y.; Zhou, H.; Ble´riot, Y.; Sinay¨, P. Eur. J.
Org. Chem. 2001, 1053–1059.
7. Barker, R.; Fletcher, H. G., Jr. J. Org. Chem. 1961, 26,
4605–4609.
8. (a) Sellier, O.; Van de Weghe, P.; Le Nouen, D.; Strehler,
C.; Eustache, J. Tetrahedron Lett. 1999, 40, 853–856; (b)
Sellier, O.; Van de Weghe, P.; Eustache, J. Tetrahedron
Lett. 1999, 40, 5859–5860.
9. Roy, R.; Das, S. K. Chem. Commun. 2000, 519–529.
10. Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413–
4450.
This compound was obtained as a foam using the
method previously described for 19; [h]D=+3 (c 0.25 in
CH3OH); 1H NMR (D2O, 400 MHz): 4.16 (d, 1H,
J=7.6 Hz, H-4), 4.06 (app t, 1H, J=2.2 Hz, H-2), 3.93
(m, 1H, H-1), 3.81 (dd, 1H, J=2.2 Hz, 7.6 Hz, H-3),
3.56 (m, 2H, H-6, H-6%), 2.00 (m, 1H, H-9%), 1.78–1.51
(m, 5H, H-7, H-7%, H-8, H-8%, H-9); 13C NMR (D2O,
100 MHz): 76.80 (C-5), 74.72 (C-2), 72.39 (C-1), 71.45
(C-4), 70.55 (C-3), 65.10 (C-6), 30.40, 29.47, 17.62 (C-7,
C-8, C-9); m/z (ES+): 245 (M+Na+, 100%).
4.20. Triacetonide 31
Diol 25 (96 mg, 0.194 mmol) was dissolved under argon
in acetone (9 mL). Camphorsulfonic acid (10 mg) and
2,2-dimethoxypropane (1 mL) were added. The reaction
mixture was stirred for 3 h at rt, quenched with triethy-
lamine (0.2 mL) and concentrated under vacuum. The
residue was dissolved in MeOH/AcOEt (10 mL, 1/1)
and stirred under H2 for 1 h in the presence of 10%
Pd/C (10 mg). The reaction mixture was filtered
through Celite, eluted with MeOH and the solvent was
evaporated. The residue was dissolved under argon in
acetone (9 mL). Camphorsulfonic acid (10 mg) and
2,2-dimethoxypropane (1 mL) were added. The reaction
mixture was stirred for 5 h at rt, quenched with triethy-
lamine (0.2 mL) and concentrated under vacuum.
Purification by flash chromatography (EtOAc/cylohex-
ane, 1:5) afforded the triacetonide 31 (40 mg, 0.116
mmol, 60% yield) as white crystals; [h]D=+15 (c 0.7 in
CHCl3); mp 127–128°C (EtOAc/cyclohexane); 1H
NMR (CDCl3, 400 MHz): 4.30 (ddd, 1H, J=5.4 Hz,
10.1 Hz, H-1), 4.19 (dd, 1H, J=5.4 Hz, 9.3 Hz, H-2),
4.17 (d, 1H, J=8.6 Hz, H-6), 3.93 (dd, 1H, J=8.1 Hz,
9.3 Hz, H-3), 3.86 (d, 1H, J=8.1 Hz, H-4), 3.78 (d, 1H,
J=8.6 Hz, H-6%), 1.93–1.68 (m, 6H, H-7, H-7%, H-8,
H-8%, H-9, H-9%), 1.51 (3H, s, CH3), 1.49 (6H, 2×s,
2×CH3), 1.46 (3H, s, CH3), 1.43 (3H, s, CH3), 1.41 (3H,
s, CH3); 13C NMR (CDCl3, 100 MHz): 82.15 (C-4),
81.66 (C-5), 78.38 (C-2), 77.57 (C-1), 76.45 (C-3), 71.08
(C-6), 35.77, 31.38 (C-7, C-9), 20.08 (C-8), 28.36, 27.53,
27.07, 26.91, 26.00, 25.88 (6×CH3); m/z (CI, NH3): 343
(M+H+, 18%); 360 (M+NH4 , 100%). Anal. calcd for
11. Kirkland, T. A.; Grubbs, R. H. J. Org. Chem. 1997, 62,
7310–7318.
+
C18H30O6: C, 63.14; H, 8.83. Found: C, 63.12; H,
8.95%.
12. (a) Freeman, F.; Robarge, R. D. Carbohydr. Res. 1986,
154, 270–274; (b) Pearson, W. H.; Hines, J. V. Tetra-
hedron Lett. 1991, 32, 5513–5516; (c) Sharma, G. V. M.;
Subash Chander, A.; Krishnudu, K.; Radha Krishna, P.
Tetrahedron Lett. 1997, 38, 9051–9054; (d) Tatiboue¨t, A.;
Rollin, P.; Martin, O. R. J. Carbohydr. Chem. 2000, 19,
641–645; (e) Pearson, W. H.; Hines, J. V. J. Org. Chem.
2000, 65, 5785–5793; (f) Postema, M. H. D.; Calimente,
D.; Liu, L.; Behrmann, T. L. J. Org. Chem. 2000, 65,
6061–6068.
Acknowledgements
We would like to thank Professor Alo¨ıs Fu¨rstner for
the generous gift of the RCM catalyst 7. We thank Dr.
Carine Duhayon from the Centre de Re´solution des
Structures (Universite´ Pierre et Marie Curie), for solv-
ing the X-ray structure of compound 31 and Dr. Denis
Lesage (Universite´ Pierre et Marie Curie) for recording
the electrospray spectra. We thank also Miss Catherine
Schu¨tz for technical help and the Swiss National Sci-
ence Foundation and the ‘Office Fe´de´ral de l’Education
et de la Science’ for financial support.
13. Chorghade, M. S.; Cseke, C. T.; Liu, P. S. Tetrahedron:
Asymmetry 1994, 5, 2251–2254.
14. Catalyst 6 was purchased from Fluka and catalyst 7 was
a generous gift from Professor A. Fu¨rstner.
15. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org.
Lett. 1999, 1, 953–956.

Y. Ble´riot et al. / Tetrahedron: Asymmetry 13 (2002) 2553–2565
2565
16. (a) Scholl, M.; Trnka, T. M.; Morgan, J. P.; Grubbs, R.
H. Tetrahedron Lett. 1999, 40, 2247–2250; (b) Briot, A.;
Bujard, M.; Gouverneur, V.; Nolan, S. P.; Mioskowski,
C. Org. Lett. 2000, 2, 1517–1519; (c) Maier, M. E.
Angew. Chem., Int. Ed. 2000, 39, 2073–2077.
Legler, G. Adv. Carbohydr. Chem. Biochem. 1990, 48,
319–384; (f) Legler, G.; Bollhagen, R. Carbohydr. Res.
1992, 233, 113–123.
22. Mehta, G.; Ramesh, S. S. Tetrahedron Lett. 2001, 42,
1987–1990.
17. Bourgeois, D.; Mahuteau, J.; Pancrazi, A.; Nolan, S. P.;
23. Kensho, I.; Yamashita, F.; Nagai, T.; Fujimoto, T.;
Nakano, Y.; Fukimura, H. Eur. Pat. Appl. (1992), Appl.
EP91-306919 19910729; Chem. Abstr. 1992, 116: 248434.
24. (a) Iwata, N.; Ishiwatari, K. Jpn Kokai–Tokkyo Koho
(2001), Appl. JP99-287620 19991008; Chem. Abstr. 2001,
134: 279953; (b) Miyatake, K.; Kensho, G.; Fujimoto, T.;
Noguchi, E.; Shinohara, M.; Takenaka, S.; Taira, T.;
Upadhaya, S. P.; Ichimoto, I.; Nakano, Y. Biosc. Bio-
technol. Biochem. 1994, 58, 756–757.
25. Billington, D. C.; Perron-Sierra, F.; Picard, I.; Beaubras,
S.; Duhault, J.; Espinal, J.; Challal, S. Bioorg. Med.
Chem. Lett. 1994, 4, 2307–2312.
26. (a) Atsumi, S.; Iinuma, H.; Nosaka, C.; Umezawa, K. J.
Antibiot. 1990, 43, 1579–1585; (b) Withers, S. G.;
Umezawa, K. Biochem. Biophys. Res. Commun. 1991,
177, 432–437.
27. (a) Tai, V. W.-F.; Fung, P.-H.; Wong, Y.-S.; Shing, T. K.
M. Tetrahedron: Asymmetry 1994, 5, 1353–1362; (b)
Marco-Contelles, J. Eur. J. Org. Chem. 2001, 1607–1618;
(c) Tatsuta, K.; Niwata, Y.; Umezawa, K.; Toshima, K.;
Nakata, M. J. Antibiot. 1991, 44, 912–914; (d) Atsumi, S.;
Nosaka, C.; Ochi, Y.; Iinuma, H.; Umezawa, K. Cancer
Res. 1993, 53, 4896–4899; (e) Nakata, M.; Chong, C.;
Niwata, Y.; Toshima, K.; Tatsuta, K. J. Antibiot. 1993,
46, 1919–1922.
28. (a) Tropea, J. E.; Molyneux, R. J.; Kaushal, G. P.; Pan,
Y. T.; Mitchell, M.; Elbein, A. D. Biochemistry 1989, 28,
2027–2034; for details see: (b) Brandi, A.; Cicchi, S.;
Cordero, F. M.; Frignoli, B.; Goti, A.; Picasso, S.; Vogel,
P. J. Org. Chem. 1995, 60, 6806–6812; (c) Picasso, S.;
Chen, Y.; Vogel, P. Carbohydr. Lett. 1994, 1, 1–8.
Prunet, J. Synthesis 2000, 6, 869–882.
18. (a) Johnson, L. K.; Grubbs, R. H.; Ziller, J. W. J. Am.
Chem. Soc. 1993, 115, 8130–8145; (b) Johnson, L. K.;
Frey, M.; Ulibarri, T. A.; Virgil, S. C.; Grubbs, R. H.;
Ziller, J. W. J. Am. Chem. Soc. 1993, 115, 8167–8177; (c)
Maughon, B. R.; Grubbs, R. H. Macromolecules 1997,
30, 3459–3469; (d) Kingsbury, J. S.; Harrity, J. P. A.;
Bonitatebus, P. J., Jr.; Hoveyda, A. H. J. Am. Chem. Soc.
1999, 121, 791–799; (e) Lee, C. W.; Grubbs, R. H. Org.
Lett. 2000, 2, 2145–2147.
19. Pearson, A. J.; Srinivasan, K. J. Org. Chem. 1992, 57,
3965–3973.
20. Selected crystal structure data for 31; crystal system
orthorhombic; space group P212121; Z=4; cell parame-
,
ters: a=5.607(7), b=17.258(11), c=19.297(15) A, h=90,
,
i=90, k=90°; radiation (Mo-Ka) u=0.710690 A; 98
variables for 588 reflections; final R=0.0820, RW=
0.0990; crystallographic data (excluding structure factors)
have been deposited at the Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC
183140. Copies of the data can be obtained free of charge
on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK [fax: (internat.) +44-1223/336-033; e-mail:
deposit@ccdc.cam.ac.uk].
21. (a) Legler, G.; Herrchen, M. FEBS Lett. 1981, 135,
139–144; (b) Cavanagh, K. J.; Fischer, R. A.; Legler, G.;
Herrchen, M.; Jones, M. Z.; Julich, E.; Sewell-Alger, R.
P.; Sinnott, M. L.; Wilkinson, F. E. Enzyme 1985, 34,
75–82; (c) El Ashry, E. S. H.; Rasked, N.; Shobier, A. H.
S. Pharmazie 2000, 55, 403–415; (d) Ley, S. V.; Sternfeld,
F.; Taylor, S. Tetrahedron Lett. 1987, 28, 225–228; (e)