Synthesis and elaboration of functionalised carbohydrate-derived spiroketals

Article abstract of DOI:10.1039/b401699h

The scope of a stereoselective three-step approach for the synthesis of sugar derived spiroketals is presented. The methodology consists of Grignard addition of vinyl- or allylmagnesium bromide to a carbohydrate lactone, followed by K-10 clay mediated gly

Full text of DOI:10.1039/b401699h

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Synthesis and elaboration of functionalised carbohydrate-derived
spiroketals
Peter A. V. van Hooft,a Farid El Oualid,b Herman S. Overkleeft,b Gijsbert A. van der Marel,b
Jacques H. van Boom*b and Michiel A. Leeuwenburghb
a TNO Prins Maurits Laboratory, P.O. Box 45, 2280 AA Rijswijk, The Netherlands
b Leiden Institute of Chemistry, Leiden University, Gorlaeus Laboratories, PO Box 9502,
2300 RA Leiden, The Netherlands. E-mail: j.boom@chem.leidenuniv.nl;
Fax: ϩ31 71 5274307; Tel: ϩ31 71 5274280
Received 5th February 2004, Accepted 8th March 2004
First published as an Advance Article on the web 5th April 2004
The scope of a stereoselective three-step approach for the synthesis of sugar derived spiroketals is presented.
The methodology consists of Grignard addition of vinyl- or allylmagnesium bromide to a carbohydrate lactone,
followed by K-10 clay mediated glycosidation with a terminal alkenol and subsequent ring-closing metathesis
of the resulting diene. The generality of this procedure is demonstrated by the synthesis of various pyranose-
and furanose-derived spiroketals, as well as more advanced tricyclic spiroketal derivatives. It is shown that
functionalisation of the double bond in the resulting spiroketals leads to fused polycyclic ethers.
Introduction
Spiroketals, particularly 1,6-dioxa-spiro[4.5]decanes and 1,7-
dioxa-spiro[5.5]undecanes, which are common structural
features of many natural products,1 have attracted consider-
able interest from synthetic organic chemists over the past
several decades. An attractive approach towards functionalised
spiroketals involves the use of carbohydrates as readily available
chiral synthons. For instance, Hanessian and Ugolini2 reported
the acid-catalysed intramolecular glycosidation of a ketose
derivative to a 1,7-dioxa-spiro[5.5]undecene. Similarly, [4.4] as
well as [4.5] spiroketals were produced by acid-catalysed trans-
ketalisation of keto-furanosides.3 Alternatively, a 1,6-dioxa-
spiro[4.5]undecane framework was constructed by radical
promoted cyclisation of C-glycosides.4 However, the spiro-
ketalisations described above lead to epimeric mixtures which
require additional acid treatment to force the equilibrium to the
thermodynamically most stable isomer. Sinaÿ and Haudrechy5
nicely evaded this drawback by predispositioning the configur-
ation at the future spirocentre through a stereoselective glyco-
sidation of a ketose derivative. The resulting ketoglycoside was
successively converted into a spiroketal via radical mediated
ring-closure.6 In line with this approach, we developed a three-
step procedure,7 comprising Grignard addition of vinyl- or
allylmagnesium bromide to perbenzylated -gluconolactone,
followed by stereoselective Montmorillonite K-10 clay8 medi-
Scheme 1 Reagents and conditions: i, vinylmagnesium bromide (1.2
ated condensation with different terminal alkenols and sub-
sequent formation of the spiroketal by ring-closing metathesis
using Grubbs’ catalyst.9 We present here the scope of this
approach in full detail by the transformation of pyranose and
furanose derived lactones into [4.4], [4.5], [4.6] and [5.5]
spiroketals, as well as the synthesis of more advanced tricyclic
compounds.
equiv.), Et2O, Ϫ78 ЊC (2: 91%). ii, Allylmagnesium bromide (1.2 equiv.),
Et2O, Ϫ78 ЊC (3: 83%). iii, Allyl alcohol (6 equiv.), K-10 clay (200
mass%), 4 Å sieves, CH2Cl2 (4: 75%, 5: 69%). iv, 6 (0.06 equiv.), toluene,
60 ЊC (7: 95%, 8: 88%, 11: 88%, 14: 95%, 15: 90%). v, PtO2, H2, EtOAc
(85%). vi, 3-Buten-1-ol (6 equiv.), K-10 clay (200 mass%), 4 Å sieves,
CH2Cl2 (10: 68%, 12: 69%, 13: 80%). vii, 4-Penten-1-ol (6 equiv.), K-10
clay (200 mass%), 4 Å sieves, CH2Cl2 (80%).
bromide afforded the known14 allylketose 3 as a mixture
of anomers (α : β = 4; 1). Next, Montmorillonite K-10 clay
mediated glycosidation of donors 2 and 3 with an excess of
allyl alcohol afforded the corresponding isomerically pure
α-ketoglycosides 4 and 5. The last step, comprising RCM of
dienes 4 and 5 using Grubbs’ catalyst 6 (6 mol%) in toluene at
60 ЊC, gave the respective spiroketal derivatives 7 and 8 in 65%
and 50% overall yield from 1. The S-configuration of the spiro-
centres in compounds 7 and 8 was unambiguously assigned by
NOESY experiments (see Scheme 1).15 In addition, the NMR-
data of saturated spiroketal 9, obtained by hydrogenation of 7
Results and discussion
In a preliminary paper7a we showed that 1,6-dioxa-(5S)-
spiro[4.5]dec-3-ene 710,11 (see Scheme 1) and 1,7-dioxa-(6S)-
spiro[5.5]undec-9-ene 811 could be assembled with a high degree
of stereoselectivity following the three-step reaction sequence
mentioned above. In the first instance, fully benzylated glu-
conolactone 112 was converted into the known13 α-epimer of
vinylketose 2 by nucleophilic addition of vinylmagnesium
bromide. Treatment of the same lactone with allylmagnesium
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 4
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 3 9 5 – 1 4 0 3
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Table 1 Examples of the K-10/RCM approach towards monosaccharide-derived spiroketals
Entry
1
Donor
Acceptor
K-10 producta
Yield (%)
70
RCM productb
Yield (%)
90c
2
3
89
66
85c
95d
4
5
54
42
87
99c
a Acceptor (6 equiv.), K-10 (200 mass%), 4 Å sieves, CH2Cl2, 20 ЊC. b 6 (0.06 equiv.), toluene, 60 ЊC. c 6 (0.06 equiv.), CH2Cl2, 20 ЊC. d 6 (0.03 equiv.),
CH2Cl2, 20 ЊC.
under the influence of platinum() oxide, were identical to
those reported by the groups of Suárez and Taylor.4d,16 Glyco-
sidation of ketoses 2 and 3 with 3-buten-1-ol and 4-penten-1-ol
and subsequent RCM as described above led to spiroketals
11,2,17 14 and 15 in 60%, 66% and 72% yields, respectively, over
the two steps.7,11
Reaction of the same lactone with allylmagnesium bromide
furnished allylketose 25 in excellent yield. Subjection of 25 to
K-10 glycosidation with allyl alcohol as well as 3-butene-1-ol
(entries 4 and 5 respectively), followed by RCM of the resulting
dienes afforded spiroketals 27 and 29 in 47% and 42% yield over
two steps.
In the next stage, the influence of the carbohydrate con-
figuration on the efficacy of the three-step methodology was
studied. Therefore, the lactones derived from fully benzylated
-fuco- and -rhamnopyranose18,19 were subjected to Grignard
addition of allylmagnesium bromide and K-10 mediated glyco-
sidation with allyl alcohol (entries 1 and 2, Table 1) as described
in Scheme 1. RCM of the resulting dienes 17 and 20 using
Grubbs’ catalyst (6 mol%) in dichloromethane at ambient tem-
perature afforded the respective spiroketals 18 and 21 (55% and
68%, respectively), the structures of which were fully assigned
by NMR-spectroscopy. Continuing our investigation, the
acid-labile furanoid 2,3;5,6-di-O-isopropylidene--manno-1,4-
lactone20 was subjected to the three-step sequence. Reaction of
this lactone with vinylmagnesium bromide led to the isolation
of the expected vinylketose 22 (entry 3) in 45% as well as a side-
product. Mass spectrometric and NMR-spectroscopic analysis
indicated that the latter compound resulted from double vinyl
addition which led to an acyclic bis-adduct.21 However, sub-
sequent glycosidation of 22 and RCM steps proceeded
smoothly to give spiroketal 24 in 64% yield over two steps.
The generality of the approach is further emphasised by its
application in the synthesis of the more complex tricyclic
spiroketal 34. Lactone 31 (see Scheme 2) was synthesised from
known22 pyranopyran compound 30 in two steps. Liberation of
the acetal function by acid hydrolysis with 3 M sulfuric acid in
acetic acid at 80 ЊC, followed by subsequent oxidation furnished
lactone 31 in 50% yield. Execution of the three-step reaction
sequence on this lactone, as described for the conversion of
2 into 7, proceeded in 20% overall yield to afford spiroketal
34, the structure of which was ascertained by NOESY-
experiments. A different tricyclic constellation, namely 37 (see
Scheme 3), was accessible through K-10-mediated glycosidation
of vinylketose 2 with sugar derived acceptor 35.23 Remarkably,
this glycosidation only proceeded in satisfactory yield when 35
was used in a 20-fold excess. RCM of the resulting disaccharide
36 with Grubbs’ catalyst 6 (6 mol%) furnished tricyclic adduct
37 in 64% yield.
Interestingly, yet another opportunity to construct oligo-
cyclic systems presents itself by elaboration of the double bond
in the spiroketals, as is demonstrated for spiroketal 8 (see
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 3 9 5 – 1 4 0 3
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opening of the crude epoxide with allylmagnesium bromide
in THF26 at 0 ЊC. The resulting alkenol 39 was isolated in
61% yield. Allylation under standard conditions, followed by
RCM using 0.5 mol% Grubbs’ catalyst 4127 in refluxing di-
chloromethane afforded tricyclic product 42 in 74% over two
steps. The structure of 42 was confirmed by NOESY-experi-
ments, of which the most important signals are depicted in
Scheme 4.
Conclusion
In this paper, the scope of a stereoselective and versatile three-
step approach towards the construction of pyranose (-gluco,
-fuco and -rhamno) and furanose (-manno) derived unsatur-
ated spiroketals is presented. The methodology has proven to
be effective for the construction of [4.4], [4.5], [5.5], [5.6] and
[5.7] spiroketals and also of the more advanced tricyclic
compounds 34 and 37. It was demonstrated that the double
bond in the newly formed spirosystem is amenable to further
elaboration, to furnish fused oxacyclic compounds such as
42. It is of interest to note that the allylic ether 42 can be sub-
jected to the same sequence of reactions, to give entrance to a
reiterative procedure.28 Its broad applicability, as well as the
potential to further elaborate the produced spiroketals, make
this three-step methodology a valuable tool in the synthesis of
natural products containing highly functionalised spiroketal
moieties.
Scheme 2 Reagents and conditions: i, a) 3 M H2SO4, HOAc, 80 ЊC, 6 h,
b) DMSO, acetic anhydride, 16 h (50%). ii, Vinylmagnesium bromide,
Et2O, Ϫ78 ЊC (42%). iii, Allyl alcohol (6 equiv.), K-10 clay (200 mass%),
4 Å sieves, CH2Cl2 (50%). iv, 6 (0.06 equiv.), CH2Cl2 (95%).
Experimental
General
Dichloromethane, dimethylsulfoxide (DMSO), ethyl acetate,
chloroform, N,N-dimethylformamide (DMF), pyridine (p.a.
grade, Baker) and tetrahydrofuran (THF, Baker, HPLC grade)
were stored over molecular sieves (4 Å). Toluene was boiled
under reflux with P2O5 for 3 h, distilled and stored over molecu-
lar sieves (4 Å). Anhydrous diethyl ether was freshly destilled
from LiAlH4 prior to use. Sulfuric acid, acetic acid, acetic
anhydride (p.a. grade, Baker), ethanol (96%, technical grade)
and acetone (Acros, p.a.) were used as received. Vinylmagne-
sium bromide (1 M in THF, Aldrich), allyl alcohol (Aldrich),
platinum() oxide (Acros), allylmagnesium bromide (1 M in
Et2O, Aldrich), 3-buten-1-ol (Aldrich), chlorotris(triphenyl-
phosphine)rhodium() ((PPh3)3Rh()Cl, Aldrich), 1,8-diaza-
bicyclo[5.4.0]undec-7-ene (DBU, Aldrich), allylmagnesium
chloride (2 M in THF, Aldrich), allyl bromide (Aldrich), and
sodium hydride (60% dispersion in mineral oil, Acros) were
used as received. Montmorillonite K-10 clay (Aldrich) was
dried (110 ЊC, 1 mm Hg, 10 h) before use. Reactions were exe-
cuted at ambient temperature unless stated otherwise. Drying
of organic layers after work-up was effected by addition of
MgSO4. TLC analysis was conducted on DC-Fertigfolien
(Schleicher & Schuell, F1500, LS254) or HPTLC aluminum
sheets (Merck, silica gel 60, F254) with detection by UV-
absorption (254 nm) and charring with 20% H2SO4in ethanol.
Column chromatography was performed either on Baker silica
gel (0.063–0.200 mm) or Merck silica gel 60 (0.040–0.063 mm).
Solvents used for column chromatography were of technical
grade and distilled before use. 1H- and 13C-spectra were
recorded on a Jeol JNM-FX-200 (200 MHz and 50.1 MHz,
respectively) or a Bruker DPX-300 (300 MHz and 75.1 MHz,
respectively). NMR shifts are reported in ppm (δ) relative to
tetramethylsilane. Mass spectrometry was performed on a
PE/SCIEX API 165 equipped with an electrospray interface.
Optical rotation values were measured at 20 ЊC on a Propol
Automatic Polarimeter at 589 nm and are given in unit of 10Ϫ1
Scheme 3 Reagents and conditions: i, 35 (20 equiv.), K-10 clay
(200 mass%), 4 Å sieves, CH2Cl2 (45%). ii, 6 (0.06 equiv.), CH2Cl2
(64%).
Scheme 4 Reagents and conditions: i, (Ph3P)3RhCl (cat.), DBU, EtOH,
60 ЊC (90%). ii, a) DMDO, CH2Cl2, 0 ЊC, b) allylmagnesium chloride,
THF, 0 ЊC (61%). iii, Allyl bromide, NaH, DMF (93%). iv. catalyst 41
(0.5 mol%), CH2Cl2, ∆ (80%).
Scheme 4). Conversion of 8 into enol ether 38 was effected in
90% yield by reaction with Wilkinson’s catalyst24 in the pres-
ence of a catalytic amount of DBU in ethanol at 60 ЊC.22a Next,
38 was treated with a freshly prepared solution of 3,3-di-
methyldioxirane (DMDO) in acetone at 0 ЊC,25 followed by
deg cm2 gϪ1
.
The atom numbering used for the bi- and tricyclic products is
given in Fig. 1.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 3 9 5 – 1 4 0 3
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(C-8); MS (ESI): calc. for C33H38O6 566.3, found m/z
589.3 (M ϩ Naϩ).
5,6,7,9-Tetra-O-benzyl-1,2,3-trideoxy-D-gluco-non-1-eno-4-
ulopyranose (3). Prepared from 1 by Grignard addition, accord-
ing to the general procedure. Colourless syrup (3.13 g, 5.40
mmol, 32 %, α/β = 4 : 1); δH (200 MHz; CDCl3; Me4Si) 7.29–
7.43 (m, 20H, CHarom), 5.99–6.03 (m, 1H, H-2), 5.30 (dd, 2H, 2x
H-1), 4.68, 4.71, 4.81, 4.97 and 5.05 (5d, 8H, CH2 Bn), 4.18
(br t, 1H, J 9.5 Hz, H-6), 4.10–4.17 (m, 1H, H-8), 3.66–3.89 (m,
2H, 2 × H-9), 3.78 (br t, 1H, J 10.2 Hz, H-7), 3.57 (br d, 1H,
J 9.5 Hz, H-5), 2.58 (d, 2H, J 6.6 Hz, H-3); δC (50 MHz; CDCl3;
Me4Si) 137.8, 138.0 and 138.4 (Cq Bn), 132.1 (C-2), 126.7–128.2
(CHarom), 119.8 (C-1), 97.6 (C-4), 71.3, 78.3, 81.2 and 83.5
(C-5,6,7,8), 73.1, 74.7, 75.1 and 75.4 (CH2 Bn), 68.5 (C-9), 42.6
(C-3); MS (ESI): calc. for C37H40O6 580.3, found m/z 603.4
(M ϩ Na)ϩ.
Fig. 1 The atom numbering used for the bi- and tricyclic products.
General procedure for the Grignard reactions
A solution of the lactone in anhydrous Et2O (5 mL mmolϪ1
)
was cooled to Ϫ78 ЊC under a nitrogen atmosphere. The
Grignard reagent (1.0 M solution, 1.2 equiv.) was added drop-
wise and the mixture was stirred at Ϫ78 ЊC until TLC analysis
(33% EtOAc–light petroleum ether) revealed completion of the
reaction. The reaction was quenched by addition of sat. NH4Cl
and extracted with Et2O. The organic layer was washed with
sat. NH4Cl, dried and concentrated. Silica gel chromatography
(10 to 30% EtOAc–light petroleum ether) yielded the ketose.
Allyl (4,5,6,8-tetra-O-benzyl-1,2-dideoxy)-ꢀ-D-gluco-oct-1-
eno-3-ulopyranoside (4). Prepared from 2 by K-10-mediated
glycosidation according to the general procedure. Colourless
syrup (238 mg, 0.39 mmol, 74%); δH (200 MHz; CDCl3; Me4Si)
7.34–7.43 (m, 20H, CHarom), 5.99–6.12 (m, 2H, J 11.0, 17.5 Hz,
H-2 and CH All), 5.69 (dd, 1H, J 1.5, 17.5 Hz, H-1), 5.40 (dd,
1H, J 1.5, 11.0 Hz, H-1), 5.35 (d, 1H, J 6.6 Hz, CH2 All), 5.23
(d, 1H, J 10.2 Hz, CH2 All), 4.68, 4.73, 4.78, 4.99, and 5.00 (5d,
8H, CH2 Bn), 4.29 (br t, 1H, J 8.8 Hz, H-5), 4.06 (t, 2H, J 5.9
Hz, CH2 All), 3.81–3.94 (m, 4H, H-6,7 and 2 × H-8), 3.50 (d,
1H, J 9.5 Hz, H-4); δC (50 MHz; CDCl3; Me4Si) 138.3, 138.4
and 138.8 (Cq Bn), 135.4 (C-2), 134.8 (CH All), 127.6–128.4
(CHarom), 118.7 (C-1), 116.6 (CH2 All), 99.8 (C-3), 71.9, 78.5,
83.0 and 84.3 (C-4,5,6,7), 73.3, 75.0, 75.6 and 75.8 (CH2 Bn),
68.8 (C-8), 63.0 (CH2 All); MS (ESI): calc. for C39H42O6 606.3,
found m/z 629.5 (M ϩ Na)ϩ.
General procedure for the K-10-mediated condensation reactions
To a flask containing Montmorillonite K-10 clay and powdered
molecular sieves 4 Å (both flame-dried under vacuum, 200
mass% each), was added a mixture of the ketose and the
acceptor (6 equiv.) in anhydrous CH2Cl2 (10 mL mmolϪ1) under
an argon atmosphere. The resulting suspension was stirred
vigorously until TLC analysis (25% EtOAc–light petroleum
ether) revealed completion of the reaction. A mixture of
methanol–pyridine (10 mL mmolϪ1, 1 : 1) was added and stir-
ring was continued for 10 min. The suspension was filtered over
Hyflo® and concentrated. Silica gel chromatography (5 to 20%
EtOAc–light petroleum ether) of the residue yielded the glyco-
sidation product.
Allyl (5,6,7,9-tetra-O-benzyl-1,2,3-trideoxy)-ꢀ-D-gluco-non-1-
eno-4-ulopyranose (5). Prepared from 3 by K-10-mediated gly-
cosidation according to the general procedure. Colourless syrup
(228 mg, 0.37 mmol, 69%); δH (200 MHz; CDCl3; Me4Si) 7.21–
7.30 (m, 20H, CHarom), 5.81–6.02 (m, 2H, H-2 and CH allyl),
5.28 (d, 1H, J 17.5 Hz, H-1), 5.05–5.14 (m, 3H, H-1 and CH2
allyl), 4.52, 4.57, 4.63, 4.71, 4.84 and 4.93 (6d, 8H, CH2 Bn),
4.14 (br t, 1H, J 9.5 Hz, H-6), 4.07 (d, 2H, J 5.8, CH2 All), 3.61–
3.77 (m, 4H, H-7,8 and 2 × H-9), 3.53 (br d, 1H, J 9.5 Hz, H-4),
2.63 (d, 2H, J 7.3 Hz, 2 × H-3);δC (50 MHz; CDCl3; Me4Si)
138.3 and 138.7 (Cq Bn), 135.0 (C-2), 133.6 (CH allyl), 127.5–
128.4 (CHarom), 118.1 (CH2 allyl), 116.4 (C-1), 101.9 (C-4), 72.0,
78.8, 81.2 and 83.6 (C-5,6,7,8), 73.3, 74.9, 75.1 and 75.5 (CH2
Bn), 68.9 (C-9), 61.7 (CH2allyl), 42.6 (C-3); MS (ESI): calc. for
C40H44O6 620.3, found m/z 643.4 (M ϩ Na)ϩ.
General procedures for ring-closing metathesis
Method A: A 0.08 M solution of the diene in anhydrous toluene
was purged for 15 min with argon. Grubbs’ catalyst 6 (0.06
equiv.) was added and the mixture was purged with argon for an
additional 15 min, after which the solution was heated to 60 ЊC.
Stirring was continued under an argon atmosphere until TLC
analysis (20% EtOAc–light petroleum ether) revealed complete
disappearance of the starting material. The mixture was
allowed to cool to room temperature and was concentrated.
The residue was subjected to silica gel chromatography (5 to
20% EtOAc–light petroleum ether) to give the product.
Method B: A 0.08 M solution of the diene in anhydrous di-
chloromethane was purged for 15 min with argon. Grubbs’
catalyst 6 (0.06 equiv.) was added and the mixture was purged
with argon for an additional 15 min. Stirring was continued
under an argon atmosphere until TLC analysis (20% EtOAc–
light petroleum ether) revealed complete disappearance of the
starting material. The mixture was concentrated, and purified
by silica gel chromatography (5 to 20% EtOAc–light petroleum
ether) to give the product.
(5S,7R,8R,9S,10R)-8,9,10-Tris-benzyloxy-7-benzyloxy-
methyl-1,6-dioxa-spiro[4.5]dec-3-ene (7). Obtained by RCM of
4, via method A of the general procedure, as a greenish syrup
(216 mg, 0.37 mmol, 95%); [α]D ϩ 67.2 Њ (c 1 in CH2Cl2); δH (300
MHz; CDCl3; Me4Si) 7.11–7.24 (m, 20H, CHarom), 6.19 (d, 1H,
J 5.8 Hz, H-4), 5.62 (m, 1H, H-3), 4.44, 4.54, 4.59, 4.71, 4.74,
4.84, 4.85 and 4.93 (8d, 8H, CH2 Bn), 4.04 (br t, 1H, J 9.5 Hz,
H-9), 3.98 (dd, 1H, J 6.6 Hz, H-11), 3.71–3.80 (m, 3H,
H-7,8,11), 3.64 (d, 1H, J 9.5 Hz, H-10), 2.25 (d, 2H, J 11.7 Hz,
2 × H-2); δC (50 MHz; CDCl3; Me4Si) 138.0 (Cq Bn), 138.3 and
138.7 (Cq Bn), 132.2 (C-4), 127.2–128.2 (C-3 and CHarom), 112.1
(C-5), 72.3, 77.8, 81.3 and 83.6 (C-7,8,9,10), 73.3 and 74.7 (CH2
Bn), 72.2 (C-2), 68.5 (CH2OBn); MS (ESI): calc. for C37H38O6
578.3, found m/z 601.3 (M ϩ Na)ϩ.
4,5,6,8-Tetra-O-benzyl-1,2-dideoxy-ꢀ-D-gluco-oct-1-eno-3-
ulopyranose (2). Prepared from 1 by Grignard addition, accord-
ing to the general procedure. Colourless syrup (3.82 g, 6.87
mmol, 91%); [α]D ϩ46.5 (c 1 in CHCl3); δH (200 MHz; CDCl3;
Me4Si) 7.14–7.28 (m, 20H, CHarom), 5.99 (dd, 1H, J 11.0
and 17.5 Hz, H-2), 5.26 and 5.60 (2d, 2H, J 10.2 and 16.8 Hz,
2 × H-1), 4.54, 4.63, 4.79 and 4.88 (4d, 8H, CH2 Bn), 4.05–4.10
(m, 1H, H-7), 4.01 (br t, 1H, J 9.5 Hz, H-5), 3.65–3.78 (m, 2H,
H-6,8), 3.46 (dd, 1H, J 3.7 and 7.3 Hz, H-8), 3.42 (br d, 1H,
J 9.5 Hz, H-4), 3.20 (br s, 1H, OH); δC (50 MHz; CDCl3; Me4Si)
138.6 (C-2), 137.7, 138.1 and 138.6 (Cq Bn), 127.4–128.2
(CHarom), 117.0 (C-1), 96.4 (C-3), 71.4, 78.0, 82.6 and 83.2
(C-4,5,6,7), 73.1, 74.8, 75.5 and 76.4 (CH2 Bn), 68.6
(2R,3R,4S,5R,6S )-3,4,5-Tris-benzyloxy-2-benzyloxymethyl-
1,7-dioxa-spiro[5.5]undec-9-ene (8). Obtained by RCM of 5 via
method A of the general procedure as a greenish syrup (634 mg,
1.1 mmol, 90%); [α]D ϩ34.2 (c 0.57 in CH2Cl2); δH (300 MHz;
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 3 9 5 – 1 4 0 3
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CDCl3; Me4Si) 7.25–7.40 (m, 20H, CHarom), 5.77 (m, 2H,
H-9,10), 4.60, 4.66, 4.71, 4.78, 4.96 and 5.07 (6d, 8H, CH2 Bn),
4.30 (br t, 1H, J 8.8 Hz, H-4), 4.22 (br s, 2H, 2 × H-8), 3.78–3.89
(m, 4H, H-2,3 and CH2OBn), 3.47 (d, 1H, J 9.5 Hz, H-5),
2.63 (d, 1H, J 17.5 Hz, H-11), 1.88 (d, 1H, J 16.8 Hz, H-11);
δC (50 MHz; CDCl3; Me4Si) 137.7, 138.0 and 138.5 (Cq Bn),
127.5–128.5 (CHarom), 123.6 (C-9), 121.2 (C-10), 97.2 (C-6),
71.6, 78.5, 82.0 and 83.3 (C-2,3,4,5), 73.2, 74.8, 75.5, and 75.7
(CH2Bn), 68.5 (CH2OBn), 59.8 (C-8), 29.9 (C-11); MS (ESI):
calc. for C38H40O6 592.3, found m/z 615.3 (M ϩ Na)ϩ.
3-Buten-1-yl
(5,6,7,9-tetra-O-benzyl-1,2,3-trideoxy)-ꢀ-D-
gluco-non-1-eno-4-ulopyranose (12). Prepared from 3 by K-10-
mediated glycosidation according to the general procedure.
Colourless syrup (181 mg, 0.29 mmol, 69%); δH (200 MHz;
CDCl3; Me4Si) 7.22–7.31 (m, 20H, CHarom), 5.80 (m, 2H, H-2
and CH Bu), 5.01–5.12 (m, 4H, 2 × H-1 and CH2 Bu), 4.53,
4.58, 4.65, 4.70, 4.85 and 4.91 (6d, 8H, CH2 Bn), 4.12 (br t, 1H,
J 9.5 Hz, H-6), 3.48–3.78 (m, 7H, H-5,7,8 and 2 × H-9 and CH2
Bu), 2.64 (m, 2H, 2 × H-3), 2.39 (m, 2H, CH2 Bu); δC (50 MHz;
CDCl3; Me4Si) 138.8 (Cq Bn), 135.0 (C-2), 133.7 (CH Bu),
127.5–128.4 (CHarom), 118.0 (CH2 Bu), 116.7 (C-1), 101.5
(C-4), 72.0, 78.8, 81.3 and 83.4 (C-5,6,7,8), 73.2, 74.8, 75.0 and
75.4 (CH2 Bn), 68.9 (C-9), 60.0 (CH2 Bu), 38.0 (C-3), 34.4 (CH2
Bu); MS (ESI): calc. for C41H46O6 634.3, found m/z 657.5 (M
ϩ Na)ϩ.
(5S,7R,8R,9S,10R)-8,9,10-Tris-benzyloxy-7-benzyloxy-
methyl-1,6-dioxa-spiro[4.5]decane (9). Compound 7 (47 mg, 81
µmol) was dissolved in anhydrous EtOAc (3 mL) and plat-
inum() oxide (10 mg) was added. The mixture was degassed
three times after which hydrogen gas was introduced. The mix-
ture was stirred for 5 h when TLC analysis (25% EtOAc–light
petroleum ether) revealed a completed conversion. The mixture
was purged with nitrogen gas, filtered over Hyflo® and concen-
trated. Silica gel chromatography (10% EtOAc–light petroleum
ether) of the residue yielded 9 as a colourless syrup (40 mg,
69 µmol, 85%); δH (200 MHz; CDCl3; Me4Si) 7.33–7.20 (m,
20H, CHarom), 4.54, 4.58, 4.71, 4.87, 4.93 and 4.99 (6d, 8H, CH2
Bn), 4.07 (br t, 1H, J 9.5 Hz, H-9), 4.04 (m, 1H, CH2OBn),
3.84–3.91 (m, 2H, H-2 and CH2OBn), 3.67–3.79 (m, 3H,
H-2,7,8), 3.58 (d, 1H, J 9.5 Hz, H-10), 1.86–1.97 (m, 4H,
2 × H-3 and 2 × H-4); δC (50 MHz; CDCl3; Me4Si) 138.0,
138.1, 138.3 and 138.7 (Cq Bn), 127.5–128.4 (CHarom), 107.4
(C-5), 71.2, 78.5, 80.0 and 84.5 (C-7,8,9,10), 75.5, 75.6 and
76.4 (CH2 Bn), 68.7 (CH2OBn), 68.1 (C-8), 33.4 (C-4), 24.0
(C-3); MS (ESI): calc. for C37H40O6 580.3, found m/z 603.4
(M ϩ Na)ϩ.
4-Penten-1-yl
(5,6,7,9-tetra-O-benzyl-1,2,3-trideoxy)-ꢀ-D-
gluco-non-1-eno-4-ulopyranose (13). Prepared from 3 by K-10-
mediated glycosidation according to the general procedure.
Colourless syrup (638 mg, 0.98 mmol, 80%); δH (200 MHz;
CDCl3; Me4Si) 7.47–7.52 (m, 20H, CHarom), 5.94–6.11 (m, 2H,
H-2 and CH Pent), 4.76, 4.85, 4.86, 4.95, 5.11, 5.13 and 5.15
(7d, 8H, CH2 Bn), 4.38 (br t, 1H, J 9.5 Hz, H-6), 3.71–4.01
(m, 7H, H-5,7,8 and 2 × H-9 and CH2 Pent), 2.86 (m, 2H,
CH2 Pent), 2.35 (m, 2H, 2 × H-3), 1.94–2.00 (m, 2H, CH2
pent); δC (50 MHz; CDCl3; Me4Si) 138.4, 138.7 and 138.9
(Cq Bn), 138.3 (CH Pent), 134.0 (C-2), 127.6–128.5 (CHarom),
118.0 (C-1), 115.0 (CH2 Pent), 101.6 (C-4), 72.1, 78.9, 81.4
and 83.6 (C-5,6,7,8), 73.4, 74.8, 75.1 and 75.5 (CH2 Bn), 69.0
(C-9), 59.8 (CH2 Pent), 38.1 (C-3), 30.6 (CH2 Pent), 29.1 (CH2
Pent); MS (ESI): calc. for C42H48O6 648.3, found m/z 671.3
(M ϩ Na)ϩ.
3-Buten-1-yl (4,5,6,8-tetra-O-benzyl-1,2-dideoxy)-ꢀ-D-gluco-
oct-1-eno-3-ulopyranoside (10). Prepared from 2 by K-10-
mediated glycosidation according to the general procedure.
Colourless syrup (223 mg, 0.36 mmol, 68%); δH (200 MHz;
CDCl3; Me4Si) 7.22–7.30 (m, 20H, CHarom), 5.92 (dd, 1H, J 11.0
and 17.5 Hz, H-2), 5.75 (dd, 1H, J 7.3 and 17.5 Hz, CH Bu),
5.56 (dd, 1H, J 1.5 and 17.5 Hz, H-1), 5.26 (dd, 1H, J 2.2 and
11.0 Hz, H-1), 5.06 (d, 1H, J 15.3 Hz, CH2 Bu), 4.97 (d, 1H,
J 5.1 Hz, CH2 Bu), 4.54, 4.60, 4.64, 485, and 4.87 (5d, 8H, CH2
Bn), 4.15 (br t, 1H, J 8.8 Hz, H-5), 3.71 (br t, 1H, J 8.8 Hz,
H-6), 3.62–3.81 (m, 2H, CH2 Bu), 3.42–3.52 (m, 3H, H-7 and
2 × H-8), 3.35 (d, 1H, J 9.5 Hz, H-4), 2.36 (dd, 2H, J 7.3
and 13.9 Hz, CH2 Bu); δC (50 MHz; CDCl3; Me4Si) 138.3, 138.5
and 138.9 (Cq Bn), 135.6 (C-2), 135.1 (CH Bu), 127.6–128.4
(CHarom), 118.5 (C-1), 116.5 (CH2 Bu), 99.5 (C-3), 71.8, 78.6,
83.0 and 84.5 (C-4,5,6,7), 73.4, 75.0, 75.5 and 75.7 (CH2 Bn),
68.9 (C-8), 61.2 (CH2 Bu), 34.2 (CH2 Bu); MS (ESI): calc. for
C40H44O6 620.3, found m/z 643.4 (M ϩ Na)ϩ.
(2R,3R,4S,5R,6S )-3,4,5-Tris-benzyloxy-2-benzyloxymethyl-
1,7-dioxa-spiro[5.6]dodec-10-ene (14). Obtained from 12 by
RCM according to the general procedure (method A) as a
colourless syrup (128 mg, 0.21 mmol, 95%); [α]D ϩ47.4 (c 1
in CH2Cl2); δH (200 MHz; CDCl3; Me4Si) 7.19–7.32 (m, 20H,
CHarom), 5.69 (m, 1H, H-11), 5.52 (m, 1H, H-10), 4.52, 4.55,
4.61, 4.70, 4.86 and 4.92 (6d, 8H, CH2 Bn), 4.07 (br t, 1H, J 9.5
Hz, H-4), 3.69–3.90 (m, 5H, H-2 and 2 × H-8 and CH2OBn),
3.63 (br t, 1H, J 9.5 Hz, H-3), 3.33 (d, 1H, J 9.5 Hz, H-5), 2.75
(d, 2H, J 16.1 Hz, H-12), 2.19–2.42 (m, 3H, H-12 and 2 × H-9);
δC (50 MHz; CDCl3; Me4Si) 138.7 (Cq Bn), 129.7 (C-11), 127.6–
128.7 (CHarom), 124.7 (C-10), 101.4 (C-6), 71.5, 78.7, 83.6 and
84.7 (C-2,3,4,5), 73.3, 74.9, and 75.6 (CH2 Bn), 68.7 (CH2OBn),
61.8 (C-8), 36.3 (C-9), 31.3 (C-12); MS (ESI): calc. for C39H42O6
606.3, found m/z 629.4 (M ϩ Na)ϩ.
(2R,3R,4S,5R,6S )-3,4,5-Tris-benzyloxy-2-benzyloxymethyl-
1,7-dioxa-spiro[5.7]tridec-11-ene (15). Obtained from 13 by
RCM according to the general procedure (method A) as a
greenish syrup (319 mg, 0.51 mmol, 90%); [α]Dϩ15.8 (c 1 in
CHCl3); δH (300 MHz; CDCl3; Me4Si) 7.30–7.41 (m, 20H,
CHarom), 5.89 (m, 2H, H-11,12), 4.68, 4.72, 4.78, 4.86, 5.00, 5.05
and 5.09 (7d, 8H, CH2 Bn), 4.19 (br t, 1H, J 8.8 Hz, H-4),
4.05 (d, 1H, J 11.7 Hz, CH2OBn), 3.59–3.84 (m, 5H, H-2,3 and
2 × H-8 and CH2OBn), 3.57 (d, 1H, J 9.5 Hz, H-5), 2.79 (dd,
1H, J 5.8 and 13.9 Hz, H-13), 2.04–2.45 (m, 4H, 2 × H-9 and
2 × H-10); δC (50 MHz; CDCl3; Me4Si) 137.8, 137.9, 138.1 and
138.6 (Cq Bn), 131.2 (C-12), 127.3–128.2 (CHarom), 126.3 (C-11),
102.0 (C-6), 72.0, 78.4, 83.5 and 84.7 (C-2,3,4,5), 73.1, 74.8, and
75.4 (CH2 Bn), 68.4 (CH2OBn), 59.2 (C-8), 35.0 (C-13), 30.7
(C-10), 23.7 (C-9); MS (ESI): calc. for C40H44O6 620.3, found
m/z 643.4 (M ϩ Na)ϩ.
(2R,3R,4S,5R,6S )-3,4,5-Tris-benzyloxy-2-benzyloxymethyl-
1,7-dioxa-spiro[5.5]undec-10-ene (11). Obtained from 10 by
RCM according to the general procedure (method A) as a
colourless syrup (188 mg, 0.32 mmol, 88%); [α]D ϩ40.4
(c 1 in CH2Cl2); δH (300 MHz; CDCl3; Me4Si) 7.06–7.68 (m,
20H, CHarom), 6.10 (dd, 1H, J 4.7 and 9.9 Hz, H-10), 5.53 (dd,
1H, J 1.6 and 10.1 Hz, H-11), 4.51, 4.62, 4.69, 4.78, 4.83 and
4.93 (6d, 8H, CH2 Bn), 4.06 (br t, 1H, J 9.3 Hz, H-4), 3.88 (ddd,
1H, J 1.9, 3.6 and 10.3 Hz, H-2), 3.86 (m, 1H, H-8), 3.75 (dd,
1H, J 3.8 and 10.8 Hz, CH2OBn), 3.65 (br t, 1H, J 9.9 and
9.0 Hz, H-3), 3.64 (dd, 1H, J 1.6 and 10.6 Hz, CH2OBn), 3.48
(br d, 1H, J 9.6 Hz, H-5), 2.43 (m, 1H, H-9), 1.89 (m, 1H, H-9);
δC (50 MHz; CDCl3; Me4Si) 138.0, 138.2, 138, 3 and 138.8
(Cq Bn), 130.3 (C-10), 127.6–128.6 (C-11 and CHarom), 95.6
(C-6), 71.0, 78.2, 82.9 and 83.2 (C-2,3,4,5), 73.4, 74.9, 75.3 and
75.7 (CH2Bn), 68.8 (CH2OBn), 58.1 (C-8), 24.2 (C-9); MS
(ESI): calc. for C38H40O6 592.3, found m/z 615.3 (M ϩ Na)ϩ,
631.4 (M ϩ K)ϩ.
5,6,7-Tri-O-benzyl-1,2,3-trideoxy-ꢀ-L-fuco-non-1-eno-4-
ulopyranose (16). Prepared from 5,6,7-tri-O-benzyl--fuco-1,5-
lactone16 by Grignard addition, according to the general pro-
cedure. Colourless syrup (1.42 g, 2.99 mmol, 87%); δH (200
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 3 9 5 – 1 4 0 3
1399

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MHz; CDCl3; Me4Si) 7.22–7.39 (m, 15H, CHarom), 5.82–5.94
(m, 1H, H-2), 5.16 (dd, 2H, J 4.4 and 5.8 Hz, 2 × H-1), 4.73 (m,
3H, CH2 Bn), 4.70, 4.98 and 4.99 (3d, each 1H, CH2 Bn), 3.78–
4.05 (m, 3H, H-5,6,8), 3.66 (d, 1H, J 1.5 Hz, H-7), 2.75 (s, 1H,
OH), 2.35–2.55 (m, 2H, 2 × H-3), 1.14 (d, 3H, J 6.6 Hz, CH3);
δC (50 MHz; CDCl3; Me4Si) 138.4 (Cq Bn), 132.9 (C-1), 127.5–
128.9 (CHarom), 119.0 (C-2), 98.0 (C-4), 77.5, 78.0 and 81.4
(C-5,6,7), 72.5, 74.4 and 75.3 (CH2 Bn), 67.1 (C-8), 43.2 (C-3),
16.9 (CH3); MS (ESI): calc. for C30H34O5 474.2, found m/z 497.2
(M ϩ Na)ϩ.
(CHarom), 118.6 (C-2), 116.3 (CH allyl), 102.4 (C-4), 69.4, 76.4,
80.4 and 82.0 (C-5,6,7,8), 72.6, 74.9, 75.1 and 75.4 (CH2 Bn),
61.0 (CH2 allyl), 36.4 (C-3), 18.2 (CH3); MS (ESI): calc. for
C33H38O5 514.3, found m/z 537.4 (M ϩ Na)ϩ.
(2S,3S,4R,5R,6R)-3,4,5-Tris-benzyloxy-2-methyl-1,7-dioxa-
spiro[5.5]undec-9-ene (21). Obtained from 20 by RCM accord-
ing to the general procedure (method B) as a greenish syrup
(1.35 g, 2.78 mmol, 85%); [α]D Ϫ27.2 (c 1 in CHCl3); δH (300
MHz; CDCl3; Me4Si) 7.31–7.43 (m, 15H, CHarom), 5.68 (s, 2H,
H-9,10), 4.66. 4.68, 4.80, 4.94 and 5.02 (5d, 6H, CH2 Bn), 4.00–
4.12 (m, 3H, H-2,3,4), 3.79 (d, 1H, J 2.2 Hz, H-5), 3.66 (dd, 2H,
J 7.3 and 16.1 Hz, H-8), 2.25 (m, 1H, H-11), 2.01 (m, 1H,
H-11), 1.35 (d, 3H, J 5.0 Hz, CH3); δC (50 MHz; CDCl3; Me4Si)
137.3, 137.6 and 137.8 (Cq Bn), 126.9–130.0 (CHarom), 121.6 and
123.9 (C-9,10), 97.4 (C-6), 78.7, 80.3 and 81.5 (C-3,4,5), 72.6,
74.9 and 75.2 (CH2 Bn), 68.9 (C-2), 59.6 (C-8), 32.2 (C-11), 17.9
(CH3); MS (ESI): calc. for C31H34O5 486.2, found m/z 509.3
(M ϩ Na)ϩ.
Allyl (5,6,7-tri-O-benzyl-1,2,3-trideoxy)-ꢀ-L-fuco-non-1-eno-
4-ulopyranose (17). Prepared from 16 by K-10-mediated glyco-
sidation according to the general procedure. Colourless syrup
(1.07 g, 2.08 mmol, 70%); δH (200 MHz; CDCl3; Me4Si) 7.26–
7.44 (m, 15H, CHarom), 5.84–6.00 (m, 2H, H-2 and CH allyl),
5.26 and 5.34 (2d, 2H, J 1.5 and 16.8 Hz, CH2 allyl), 5.12 and
5.17 (2d, 2H, J 1.5 and 10.2 Hz, 2 × H-1), 4.71, 4.74 and 5.00
(3d, each 1H, CH2 Bn), 4.78 and 5.04 (m, 3H, CH2 Bn), 3.99–
4.18 (m, 3H, H-5,6,8), 3.80 (dd, 2H, J 6.6 and 13.1 Hz, CH2
allyl), 3.71 (d, 1H, J 2.2 Hz, H-7), 2.66 (m, 2H, H-3), 1.20
(d, 3H, J 5.8 Hz, CH3); δC (50 MHz; CDCl3; Me4Si) 138.9 and
139.2 (Cq Bn), 135.5 (C-1), 134.2 (CH2 allyl), 127.0–128.8
(CHarom), 117.5 (C-2), 116.2 (CH allyl), 102.1 (C-4), 78.0, 78.2
and 81.2 (C-5,6,7), 72.7, 74.5 and 75.1 (CH2 Bn), 67.5 (C-8),
61.6 (CH2 allyl), 39.0 (C-3), 16.9 (CH3); MS (ESI): calc. for
C33H38O5 514.3, found m/z 537.4 (M ϩ Na)ϩ.
1,2-Dideoxy-4,5;7,8-di-O-isopropylidene-ꢀ-D-manno-oct-1-
eno-3-ulofuranose (22). Prepared from 2,3;5,6-di-O-isopropyl-
idene--manno-1,4-lactone19 by Grignard addition, according
to the general procedure. Colourless syrup (1.34 g, 4.7 mmol,
45%); δH (200 MHz; CDCl3; Me4Si) 5.89 (dd, 1H, J 10.9 and
17.5 Hz, H-2), 5.41 (dd, 1H, J 1.5 and 17.5 Hz, H-1), 5.20 (dd,
1H, J 1.5 and 10.9 Hz, H-1), 4.72 (dd, 1H, J 2.9 and 5.1 Hz,
H-5), 4.34 (d, 1H, J 5.8 Hz, H-4), 4.25 (m, 1H, H-7), 4.02 (dd,
1H, J 3.6 and 7.3 Hz, H-8), 3.86–3.97 (m, 3H, H-6,8 and OH),
1.17, 1.23, 1.31 and 1.32 (4s, each 3H, CH3); δC (50 MHz;
CDCl3; Me4Si) 136.2 (C-2), 117.0 (C-1), 112.4 (C-3), 104.1 and
108.7 (Cq), 73.1, 78.9, 80.1 and 86.5 (C-4,5,6,7), 66.2 (C-8),
24.1, 25.0, 25.6 and 26.5 (CH3); MS (ESI): calc. for C14H22O6
286.1, found m/z 309.1 (M ϩ Na)ϩ.
(2S,3R,4R,5S,6R)-3,4,5-Tris-benzyloxy-2-methyl-1,7-dioxa-
spiro[5.5]undec-9-ene (18). Obtained from 17 by RCM accord-
ing to the general procedure (method B) as a greenish syrup
(0.90 g, 1.85 mmol, 90%); [α]D Ϫ51.4 (c 1 in CHCl3); δH (300
MHz; CDCl3; Me4Si) 7.30–7.24 (m, 15H, CHarom), 5.66 (s, 2H,
H-9,10), 4.71, 4.99 and 5.00 (3d, each 1H, CH2 Bn), 4.77 (s, 3H,
CH2 Bn), 4.04–4.19 (m, 3H, H-2,4,5), 3.80 (dd, 2H, J 10.2 and
15.3 Hz, H-8), 3.69 (d, 1H, J 1.5 Hz, H-3), 2.57 (m, 1H, H-11),
1.82 (m, 1H, H-11), 1.16 (d, 3H, J 6.6 Hz, CH3); δC (50 MHz;
CDCl3; Me4Si) 138.2, 138.7 and 138.8 (Cq Bn), 127.6–128.7
(CHarom), 121.7 and 123.8 (C-9,10), 97.6 (C-6), 78.1, 78.5 and
80.9 (C-3,4,5), 72.7, 74.6 and 75.9 (CH2 Bn), 67.1 (C-2), 60.3
(C-8), 30.4 (C-11), 16.9 (CH3); MS (ESI): calc. for C31H34O5
486.2, found m/z 509.3 (M ϩ Na)ϩ.
Allyl (1,2-dideoxy-4,5;7,8-di-O-isopropylidene)-ꢀ-D-manno-
oct-1-eno-3-ulofuranose (23). Prepared from 22 by K-10-
mediated glycosidation according to the general procedure.
Colourless syrup (0.73 g, 2.24 mmol, 66%); δH (200 MHz;
CDCl3; Me4Si) 5.52–5.72 (m, 2H, H-2 and CH allyl), 5.31 (dd,
1H, J.2.2 and 21.9 Hz, H-1), 5.16 (dd, 1H, J 2.2 and 16.1 Hz,
H-1), 4.98 (br t, 2H, CH2 allyl), 4.67 (dd, 1H, J 3.6 and 5.8 Hz,
H-5), 4.37 (d, 1H, J 5.8 Hz, H-4), 4.25 (dd, 1H, J 6.6 and 13.1
Hz, H-8), 3.82–3.99 (m, 3H, H-6,7,8), 3.64 (m, 2H, CH2 allyl),
1.14, 1.21, 1.26 and 1.28 (4s, each 3H, CH3); δC (50 MHz;
CDCl3; Me4Si) 134.4 (CH allyl), 132.6 (C-2), 118.8 (C-1), 115.9
(CH2 allyl), 112.3 (C-3), 107.8 and 108.7 (Cq), 72.9, 79.1, 79.9
and 86.3 (C-4,5,6,7), 66.6 (C-8), 62.4 (CH2 allyl), 24.3, 25.0,
25.6 and 26.5 (CH3); MS (ESI): calc. for C17H26O6 326.2, found
m/z 349.0 (M ϩ Na)ϩ.
5,6,7-Tri-O-benzyl-1,2,3-trideoxy-ꢀ-L-rhamno-non-1-eno-4-
ulopyranose (19). Prepared from 5,6,7-tri-O-benzyl--rhamno-
1,5-lactone18 by Grignard addition, according to the general
procedure. Colourless syrup (1.49 g, 3.14 mmol, 90%); δH (200
MHz; CDCl3; Me4Si) 7.51–7.59 (m, CHarom), 6.00–6.12 (m,
1H, H-2), 4.88–5.45 (m, 8H, 2 × H-1 and CH2 Bn), 4.38
(d, 1H, J 9.5 Hz, H-6), 3.89–4.20 (m, 3H, H-5,7,8), 3.05 (s, 1H,
OH), 2.93 (dd, 1H, J 5.1 and 13.9 Hz, H-3), 2.54 (dd, 1H,
J 9.5 and 13.2 Hz, H-3), 1.56 (d, 3H, J 5.8 Hz, CH3);
δC (50 MHz; CDCl3; Me4Si) 138.8, 138.9 (Cq Bn), 132.7 (C-1),
127.7–128.7 (CHarom), 120.6 (C-2), 98.0 (C-4), 68.8, 77.7, 80.7
and 81.9 (C-5,6,7,8), 72.7, 74.8 and 75.3 (CH2 Bn), 42.8 (C-3),
18.3 (CH3); MS (ESI): calc. for C30H34O5 474.2, found m/z 497.3
(M ϩ Na)ϩ.
(2R,3S,4S,5S )-3,4-Dihydroxy-3,4-O-isopropylidene-2-({(R)-
1,2-dihydroxy-1,2-O-isopropylidene}ethyl)-1,6-dioxa-spiro-
[4.4]non-8-ene (24). Obtained from 23 by RCM according to the
general procedure (method B) as a greenish syrup (0.63 g, 2.11
mmol, 95%); [α]D Ϫ10.4 (c 1 in CHCl3); δH (600 MHz; CDCl3;
Me4Si) 6.17 (d, 1H, J 6.0 Hz, H-9), 5.73 (m, 1H, H-8), 4.76 (dd,
1H, J 4.1 and 5.4 Hz, H-3), 4.58 (d, 1H, J 14.0 Hz, H-7), 4.48
(d, 1H, J 13.9 Hz, H-7), 4.46 (d, 1H, J 5.9 Hz, H-4), 4.23 (m,
1H, CH Et), 3.95 (t, 1H, J 8.7 Hz, CH2 Et), 3.86–3.90 (m, 2H,
H-2 and CH2 Et), 1.21, 1.24, 1.32 and 1.38 (4s, each 3H, CH3);
δC (50 MHz; CDCl3; Me4Si) 132.6 (C-9), 124.5 (C-8), 119.2
(C-5), 108.8 and 112.4 (Cq), 72.9, 79.9 and 85.7 (C-2,3,4 and
CH Et), 74.6 (C-7), 66.8 (CH2 Et), 24.3, 25.0, 25.7 and 26.7
(CH3); MS (ESI): calc. for C15H22O6 298.1, found m/z 321.0
(M ϩ Na)ϩ, 337.2 (M ϩ K)ϩ.
Allyl (5,6,7-tri-O-benzyl-1,2,3-trideoxy)-ꢀ-L-rhamno-non-1-
eno-4-ulopyranose (20). Prepared from 19 by K-10-mediated
glycosidation according to the general procedure. Colourless
syrup (1.43 g, 2.78 mmol, 89%); δH (200 MHz; CDCl3; Me4Si)
7.50–7.65 (m, 15H, CHarom), 5.83–6.20 (m, 2H, H-2 and CH
allyl), 5.49 (d, 1H, J 16.8 Hz, H-1), 5.17 (d, 1H, CH2 Bn), 4.90–
5.39 (m, 7H, H-1, CH2 allyl and Bn), 4.79 (d, 1H, CH2 Bn), 4.39
(d, 1H, J 8.8 Hz, H-6), 4.20 (br s, 2H, 2 × H-10), 4.015 (d, 1H,
J 2.9 Hz, H-5), 3.83–4.00 (m, 2H, H-7,8), 3.07 (dd, 1H, J 7.3
and 15.3 Hz, H-3), 2.76 (dd, 1H, J 5.8 and 15.3 Hz, H-3), 1.57
(d, 3H, J 5.1 Hz, CH3); δC (50 MHz; CDCl3; Me4Si) 138.7, 138.8
and 139.0 (Cq Bn), 134.4 (CH2 allyl), 132.7 (C-1), 127.6–128.5
1,2,3-Trideoxy-5,6;8,9-di-O-isopropylidene-ꢀ-D-manno-non-1-
eno-4-ulofuranose (25). Prepared from 2,3;5,6-di-O-isopropyl-
idene--manno-1,4-lactone19 by Grignard addition, according
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 3 9 5 – 1 4 0 3
1400

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to the general procedure. Colourless syrup (1.65 g, 5.50 mmol,
95%); δH (200 MHz; CDCl3; Me4Si) 5.75–5.96 (m, 1H, H-2),
5.23 (dd, 2H, J 10.2 and 17.5 Hz, 2 × H-1), 4.84 (dd, 1H, J 3.7
and 4.8 Hz, H-6), 4.49 (d, 1H, J 6.6 Hz, H-5), 4.37 (m,
2H, H-8,9), 3.97–4.20 (m, 3H, H-7,9 and OH), 2.52 (d, 2H,
J 6.6 Hz, 2 × H-3), 1.34, 1.38, 1.45 and 1.49 (4s, each 3H, CH3);
δC (50 MHz; CDCl3; Me4Si) 123.4 (C-2), 119.0 (C-1), 112.2
(C-4), 105.1 and 108.7 (Cq), 73.0, 78.6, 79.9 and 84.8
(C-5,6,7,8), 66.3 (C-9), 39.6 (C-3), 24.1, 24.9, 25.5 and 26.5
(CH3); MS (ESI): calc. for C15H24O6 300.2, found m/z 323.2
(M ϩ Na)ϩ.
(m, 1H, CH Et), 4.03 (dd, 1H, J 6.3 and 8.7 Hz, CH2 Et), 3.94
(dd, 1H, J 4.3 and 8.7 Hz, CH2 Et), 3.89 (dd, 1H, J 2.2 and 12.0
Hz, H-7), 3.75 (dd, 1H, J 3.8 and 8.2 Hz, H-2), 3.55 (dd, 1H,
J 3.7 and 12.3 Hz, H-7), 2.66 (dd, 1H, J 6.5 and 16.3 Hz, H-11),
2.46 (dd, 1H, J 5.3 and 16.3 Hz, H-11), 2.38–2.43 (m, 1H, H-8),
2.17 (br d, 1H, J 17.2 Hz, H-8), 1.26, 1.31, 1.38 and 1.42 (4s,
each 3H, CH3); δC (50 MHz; CDCl3; Me4Si) 130.0 (C-10), 124.3
(C-9), 112.3 (Cq), 108.9 (C-5), 72.9, 78.6, 79.9 and 85.4 (C-2,3,4
and CH Et), 67.1 (CH2 Et), 60.4 (C-7), 31.8 (C-11), 31.1 (C-8),
24.3, 25.0, 25.7 and 26.7 (CH3); MS (ESI): calc. for C17H26O6
326.2, found m/z 349.1 (M ϩ Na)ϩ.
Allyl (1,2,3-trideoxy-5,6;8,9-di-O-isopropylidene)-ꢀ-D-manno-
non-1-eno-4-ulofuranose (26). Prepared from 25 by K-10-
mediated glycosidation according to the general procedure.
Colourless syrup (0.60 g, 1.76 mmol, 54%); δH (200 MHz;
CDCl3; Me4Si) 5.64–5.84 (m, 2H, H-2 and CH allyl), 5.19 (m,
1H, H-1), 4.97–5.10 (m, 3H, H-1 and CH2 allyl), 4.71 (dd, 1H,
J 4.0 and 5.8 Hz, H-6), 4.38 (d, 1H, J 5.8 Hz, H-5), 4.24–4.30
(m, 1H, H-9), 3.94–4.03 (dd, 1H, J 6.2 and 8.4 Hz, H-8), 3.79–
3.90 (m, 3H, H-9 and CH2 allyl), 3.72 (dd, 1H, J 3.7 and 7.7 Hz,
H-7), 2.51 (d, 2H, J 7.7 Hz, 2 × H-3), 1.23, 1.27, 1.34 and 1.38
(4s, each 3H, CH3); δC (50 MHz; CDCl3; Me4Si) 134.3 (CH
allyl), 132.1 (C-2), 117.6 (C-1), 116.1 (CH2 allyl), 112.2 (C-4),
108.7 and 108.9 (Cq), 72.8, 79.2, 79.8 and 84.6 (C-5,6,7,8), 66.7
(C-9), 61.3 (CH2 allyl), 34.2 (C-3), 24.3, 25.0, 25.7 and 26.6
(CH3); MS (ESI): calc. for C18H28O6 340.2, found m/z 363.2
(M ϩ Na)ϩ.
(1R,3R,4R,5S,6R)-4,5-Bis-benzyloxy-3-hydroxy-3-vinyl-2,7-
dioxa-bicyclo[4.4.0]dec-9-ene (32). Bicyclic methyl glycoside
3022 (630 mg, 1.7 mmol) was dissolved in acetic acid (20 ml) and
3 M sulfuric acid (2.4 ml). The mixture was stirred at 80 ЊC for
6 h, then allowed to cool to room temperature and diluted with
ethyl acetate (30 ml). The organic phase was washed with sat.
NaHCO3 until pH 7, dried, filtered and concentrated. The resi-
due was purified by silica gel chromatography (15% EtOAc–
light petroleum ether). The purified lactol was dissolved in di-
methylsulfoxide–acetic anhydride 2 : 1 v/v (6 ml) and stirred for
17 h, when TLC analysis (25% EtOAc–light petroleum ether)
revealed complete consumption of the starting material. The
mixture was concentrated, dissolved in ethyl acetate and
extracted with sat. NaHCO3. Organics were dried, filtered and
concentrated to leave a brown syrup (300 mg, 0.8 mmol, 50%),
which was subjected to a Grignard reaction with vinylmagne-
sium bromide as described in the general procedure to give 32
as a colourless syrup (117 mg, 0.30 mmol, 21%); δH (200 MHz;
CDCl3; Me4Si) 7.26–7.31 (m, 10H, CHarom), 5.89 (dd, 1H, J 10.2
and 17 Hz, CH vinyl), 5.68–5.77 (m, 2H, H-9,10), 5.59 (dd, 1H,
J 1.5 and 16.8 Hz, CH2 vinyl), 5.28 (dd, 1H, J 1.5 and 10.2 Hz,
CH2 vinyl), 4.61, 4.77, 4.82 and 4.98 (4d, each 1H, CH2 Bn),
4.48 (m, 1H, H-1), 4.25 (br s, 2H, 2 × H-8), 3.89 (dd, 1H, J 8.8
and 9.5 Hz, H-5), 3.43 (d, 1H, J 8.8 Hz, H-4), 3.33 (dd, 1H,
J 8.8 and 9.5 Hz, H-6); δC (50 MHz; CDCl3; Me4Si) 138.8 (CH
vinyl), 127.7–128.7 (C-9 and CHarom), 126.1 (C-10), 117.0 (CH2
vinyl), 96.2 (C-3), 65.1, 78.8, 80.5 and 82.7 (C-1,4,5,6), 74.9 and
75.8 (CH2 Bn), 66.0 (C-8); MS (ESI): calc. for C24H26O5 394.2,
found m/z 417.3 (M ϩ Na)ϩ.
(2R,3S,4S,5S )-3,4-Dihydroxy-3,4-O-isopropylidene-2-({(R)-
1,2-dihydroxy-1,2-O-isopropylidene}ethyl)-1,6-dioxa-spiro[4.5]-
dec-8-ene (27). Obtained from 26 by RCM according to the
general procedure (method A) as a colourless syrup (0.48 g,
1.54 mmol, 87%); [α]Dϩ58.2 (c 1 in CHCl3); δH (300 MHz;
CDCl3; Me4Si) 5.72 (br s, 2H, H-8,9), 4.82 (dd, 1H, J 3.6 and
5.8 Hz, H-3), 4.43 (d, 1H, J 5.8 Hz, H-4), 4.35–4.40 (m, 1H,
CH2 Et), 3.95–4.18 (m, 4H, 2 × H-7 and CH and CH2 Et), 3.85
(dd, 1H, J 3.7 and 8.0 Hz, H-2), 2.50 (dd, 1H, J 1.5 and 19 Hz,
H-10), 2.12 (dd, 1H, J 2.2 and 17.5 Hz, H-10), 1.33, 1.36, 1.44
and 1.46 (4s, each 3H, CH3); δC (50 MHz; CDCl3; Me4Si) 124.2
(C-8), 121.6 (C-9), 108.9 and 112.1 (Cq), 104.6 (C-5), 72.8, 79.3,
79.8 and 85.5 (C-2,3,4 and CH Et), 67.0 (CH2 Et), 59.8 (C-7),
28.6 (C-10), 24.4, 24.9, 25.7 and 26.6 (CH3); MS (ESI): calc. for
C16H24O6 312.2, found m/z 335.2 (M ϩ Na)ϩ.
(1R,3R,4R,5S,6R)-3-Allyloxy-4,5-bis-benzyloxy-3-vinyl-2,7-
dioxa-bicyclo[4.4.0]dec-9-ene (33). Prepared from 32 by K-10-
mediated glycosidation according to the general procedure.
Colourless syrup (65 mg, 0.15 mmol, 50%); δH (200 MHz;
CDCl3; Me4Si) 7.22–7.40 (m, 10H, CHarom), 5.73–6.00 (m, 2H,
CH vinyl and allyl), 5.52 (dd, 1H, J 2.2 and 17.5 Hz, CH2 allyl),
5.27 (dd, 1H, J 1.5 and 16.8 Hz, CH2 vinyl), 5.26 (dd, 1H, J 2.2
and 11.0 Hz, CH2 allyl), 5.12 (dd, 1H, J 1.5 and 10.2 Hz, CH2
vinyl), 4.62, 4.78, 4.91 and 4.96 (4d, each 1H, CH2 Bn), 4.26
(br s, 2H, 2 × H-8), 4.18 (m, 1H, H-1), 4.06 (dd, 1H, J 8.8 and
9.5 Hz, H-5), 3.94 (m, 2H, CH2 allyl), 3.35 (d, 1H, J 8.8 Hz,
H-4), 3.31 (dd, 1H, J 8.8 and 9.5 Hz, H-6); MS (ESI): calc. for
C27H30O5 434.2, found m/z 457.2 (M ϩ Na)ϩ.
3-Buten-1yl (1,2,3-trideoxy-5,6;8,9-di-O-isopropylidene)-ꢀ-D-
manno-non-1-eno-4-ulofuranose (28). Prepared from 25 by
K-10-mediated glycosidation according to the general pro-
cedure. Colourless syrup (0.30 g, 0.85 mmol, 42%); δH (200
MHz; CDCl3; Me4Si) 5.68–5.81 (m, 2H, H-2 and CH Bu), 5.00–
5.19 (m, 4H, 2 × H-1 and CH2 Bu), 4.79 (dd, 1H, J 4.4 and 5.8
Hz, H-6), 4.43 (d, 1H, J 5.8 Hz, H-5), 4.32–4.39 (m, 1H, H-8),
4.10 (dd, 1H, J 6.6 and 8.8 Hz, H-9), 3.97 (dd, 1H, J 4.4 and 8.8
Hz, H-9), 3.80 (dd, 1H, J 3.7 and 8.0 Hz, H-7), 3.47 (br t, 2H,
J 6.6 Hz, CH2 Bu), 2.56–2.61 (m, 2H, 2 × H-3), 2.50 (dd, 2H,
J 6.6 and 13.1 Hz, CH2 Bu), 1.32, 1.37, 1.45 and 1.47 (4s,
each 3H, CH3); δC (50 MHz; CDCl3; Me4Si) 135.3 (CH Bu),
132.3 (C-2), 117.6 (C-1), 116.4 (CH2 Bu), 112.3 (C-4), 108.7 and
109.0 (Cq), 72.9, 79.0, 79.9 and 84.6 (C-5,6,7,8), 66.9 (C-9), 59.6
(CH2 Bu), 34.1 (C-3), 34.0 (CH2 Bu), 24.4, 25.1, 25.8 and 26.7
(CH3); MS (ESI): calc. for C19H30O6 354.2, found m/z 377.2
(M ϩ Na)ϩ.
(1R,3S,4R,5S,6R)-4,5-Bis-benzyloxy-2,7-dioxa-bicyclo[4.4.0]-
dec-9-enylspiro-3,2Ј-[2Ј,5Ј-dihydrofuran] (34). Obtained from 33
by RCM according to the general procedure (method B) as a
greenish syrup (58 mg, 0.14 mmol, 95%); δH (300 MHz; CDCl3;
Me4Si) 7.20–7.29 (m, 10H, CHarom), 6.26 (m, 1H, H-3Ј), 5.77
(m, 2H, H-9,10), 5.55 (m, 1H, H-4Ј), 4.77 (br s, 2H, 2 × H-5Ј),
4.59, 4.80 and 4.98 (3d, 4H, CH2 Bn), 4.40 (m, 1H, H-1),
4.26 (m, 2H, 2 × H-8), 3.97 (br t, 1H, J 9.5 Hz, H-6), 3.61 (d,
1H, J 8.8 Hz, H-4), 3.33 (dd, 1H, J 8.8 and 9.5 Hz, H-5);
δC (50 MHz; CDCl3; Me4Si) 138.1 and 138.9 (Cq Bn), 132.6
(C-3Ј), 126.1–128.1 (C-4Ј,9,10 and CHarom), 112.8 (C-3), 78.9,
80.8 and 81.2 (C-4,5,6), 75.1 and 75.9 (CH2 Bn), 66.1 (C-8),
66.0 (C-1); MS (ESI): calc. for C25H26O5 406.2, found m/z 429.1
(M ϩ Na)ϩ.
(2R,3S,4S,5S )-3,4-Dihydroxy-3,4-O-isopropylidene-2-({(R)-
1,2-dihydroxy-1,2-O-isopropylidene}ethyl)-1,6-dioxa-spiro[4.6]-
undec-9-ene (29). Obtained from 28 by RCM according to the
general procedure (method B) as a greenish syrup (0.27 g, 0.83
mmol, 99%); [α]Dϩ9.2 (c 1 in CHCl3); δH (600 MHz; CDCl3;
Me4Si) 5.65 (m, 1H, H-9), 5.53 (m, 1H, H-10), 4.74 (dd, 1H,
J 3.8 and 5.9 Hz, H-3), 4.36 (d, 1H, J 5.9 Hz, H-4), 4.29–4.32
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 3 9 5 – 1 4 0 3
1401

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3-O-(4Ј,5Ј,6Ј,8Ј-Tetra-O-benzyl-1Ј,2Ј-dideoxy-ꢀ-D-gluco-oct-
1Ј-eno-3Ј-ulopyranosyl)-5,6-dideoxy-1,2-O-isopropylidene-ꢀ-D-
xylo-hex-5-enofuranoside (36). K-10 mediated glycosidation, as
described in the general procedure, of 2 (0.39 g, 0.68 mmol)
10 min, TLC analysis (20% EtOAc–light petroleum ether)
showed complete consumption of the starting material. The
mixture was concentrated, redissolved in anhydrous toluene
(5 mL) and concentrated again. The crude epoxide was dissol-
ved in THF (5 mL), cooled to 0 ЊC under argon atmosphere,
after which a solution of allylmagnesium chloride (0.58 mL,
2 M, 1.16 mmol) was added. After stirring for 15 min., TLC
analysis (33% EtOAc/light petroleum ether) showed a nearly
completed reaction. The reaction was quenched by addition of
sat. NH4Cl and extracted with diethyl ether. The organic layer
was washed with sat. NH4Cl, dried and concentrated. Silica gel
chromatography (16 to 40% EtOAc–light petroleum ether)
yielded compound 39 as a colourless syrup (246 mg, 0.37 mmol,
61%); δC (50 MHz; CDCl3; Me4Si) 137.7, 138.1 and 138.5 (Cq
Bn), 134.8 (CH allyl), 127.4–128.2 (CHarom), 117.1 (CH2 allyl),
98.3 (C-6), 73.2, 74.8, 75.3 and 75.7 (CH2 Bn), 68.7 (CH2OBn),
65.9, 71.1, 77.9, 78.5, 82.9 and 83.7 (C-2,3,4,5,8,9), 37.4 (CH2
allyl), 25.0 (C-11), 21.8 (C-10); MS (ESI): calc. for C41H46O7
650.3, found m/z 673.3 (M ϩ Na)ϩ.
with
5,6-dideoxy-1,2-O-isopropylidene-α--xylo-hex-5-eno-
furanose22 (35, 0.76 g, 4.09 mmol) afforded 36 as a colourless
syrup (0.23 g, 0.31 mmol, 45%); δH (200 MHz; CDCl3; Me4Si)
7.18–7.35 (m, 20H, CHarom), 6.21 (m, 1H, H-5), 5.95 (dd, 1H,
J 11.0 and 17.5 Hz, H-2Ј), 5.93 (dd, 1H, J 2.2 and 12.4 Hz,
H-6), 5.64 (dd, 1H, J 2.2 and 17.5 Hz, H-6), 5.38 (d, 1H,
J 2.9 Hz, H-1), 5.31–5.39 (m, 1H, H-1), 5.17 (dd, 1H, J 1.5 and
10.2 Hz, H-1), 4.52–4.91 (m, 10H, H-3,4 and CH2 Bn), 4.26
(d, 1H, J 2.9 Hz, H-2), 4.07 (t, 1H, J 9.5 Hz, H-5Ј), 3.94 (m,
1H, H-8Ј), 3.63–3.82 (m, 2H, H-7Ј,8Ј), 3.53 (t, 1H, J 9.5 Hz,
H-6Ј), 3.30 (d, 1H, J 9.5 Hz, H-4Ј), 1.18 and 1.47 (2s, each
3H, CH3); δC (50 MHz; CDCl3; Me4Si) 137.9 and 138.5 (Cq
Bn), 133.2 and 135.0 (C-2Ј,5), 127.1–128.4 (CHarom), 119.5
and 119.7 (C-1Ј,6), 111.2 (Cq), 104.7 (C-1), 100.5 (C-3Ј),
73.5, 75.2, 75.4 and 75.6 (CH2 Bn), 72.5, 78.4, 78.6, 82.3, 82.5,
83.6 and 85.1 (C-2,3,4,4Ј,5Ј,6Ј,7Ј), 69.1 (C-8Ј), 26.0 and 26.7
(CH3); MS (ESI): calc. for C45H50O9 734.3, found m/z 757.4
(M ϩ Na)ϩ.
(2R,3R,4S,5R,6S,8R,9S )-8-Allyl-9-allyloxy-3,4,5-tris-benzyl-
oxy-2-benzyloxymethyl-1,7-dioxa-spiro[5.5]undecane (40). To a
solution of compound 39 (246 mg, 0.38 mmol) in anhydrous
N,N-dimethylformamide (3 mL) were added allyl bromide
(50 µl, 0.57 mmol) and sodium hydride (20 mg, 60% dispersion
in oil, 0.49 mmol). After stirring for 16 h, TLC analysis (33%
EtOAc–light petroleum ether) showed complete disappearance
of 39. The excess sodium hydride was destroyed by addition of
methanol (5 mL). The mixture was partitioned between diethyl
ether and brine. The organic phase was extracted with brine,
dried and concentrated. Purification was effected by silica gel
chromatography (20% EtOAc–light petroleum ether) to afford
40 as a colourless syrup (242 mg, 0.35 mmol, 93%); δC (50 MHz;
CDCl3; Me4Si) 138.2 and 138.7 (Cq Bn), 135.1 (CH allyl),
127.3–128.2 (CHarom), 116.1 and 116.9 (CH2 allyl), 98.6 (C-6),
73.1, 74.7, 75.3 and 75.5 (CH2 Bn), 70.9, 72.9, 75.4, 78.6, 82.9
and 84.0 (C-2,3,4,5,8,9), 69.1 (CH2 allyl), 68.8 (CH2OBn), 37.6
(CH2 allyl), 25.5 (C-11), 19.4 (C-10); MS (ESI): calc. for
C44H50O7 690.3, found m/z 713.3 (M ϩ Na)ϩ.
2,3,4,6-Tetra-O-benzyl-ꢀ-D-glucopyranosylspiro-1Ј-[(3ЈS,4ЈR,
5ЈR,7ЈR)-4Ј,5Ј-dihydroxy-4Ј,5Ј-O-isopropylidene-2Ј,6Ј-dioxa-
bicyclo[3.4.0]non-8Ј-ene] (37). Obtained from 36 by RCM
according to the general procedure (method B) as a colour-
less syrup (85 mg, 0.12 mmol, 64%); [α]Dϩ64.4 (c 1 in CHCl3);
δH (300 MHz; CDCl3; Me4Si) 7.12–7.31 (m, 20H, CHarom), 6.18
(dd, 1H, J 5.1 and 10.2 Hz, H-9Ј), 6.08 (d, 1H, J 3.6 Hz, H-1),
5.78 (d, 1H, J 10.2 Hz, H-8Ј), 4.69 (br s, 2H, CH2 Bn), 4.47,
4.53, 4.60, 4.81, 4.83 and 4.91 (6d, each 1H, CH2 Bn), 4.40 (m,
1H, H-5Ј), 4.29 (d, 1H, J 3.0 Hz, H-4Ј), 4.05 (t, 1H, J 8.8 Hz,
H-3), 3.61–3.88 (m, 4H, H-1,7 and 2 × H-8), 3.71 (t, 1H,
J 8.8 Hz, H-4), 3.51 (d, 1H, J 8.8 Hz, H-2), 1.32 and 1.52
(2s, each 3H, CH3); δC (50 MHz; CDCl3; Me4Si) 137.9, 138.1
and 138.7 (Cq Bn), 127.7–128.3 (CHarom), 125.4 and 132.2
(C-8Ј,9Ј), 111.3 (Cq), 105.7 (C-3Ј), 95.5 (C-1Ј), 73.4, 74.7, 74.9
and 75.5 (CH2 Bn), 69.5, 71.8, 73.7, 77.8, 82.6 and 84.2
(C-1Ј,2,3,4,4Ј,5,5Ј), 68.3 (C-6), 26.1 and 26.8 (CH3); MS (ESI):
calc. for C43H46O9 706.3, found m/z 729.5 (M ϩ Na)ϩ.
2,3,4,6-Tetra-O-benzyl-ꢀ-D-glucopyranosylspiro-3Ј-[(1ЈR,
6ЈS )-2Ј,7Ј-dioxa-bicyclo[4.5.0]undec-9Ј-ene] (42). To a solution
of diene 40 (240 mg, 0.35 mmol) in anhydrous dichloromethane
(5 mL) was added Grubbs’ catalyst 4127 (0.1 mg, 0.18 µmol)
under argon atmosphere and the mixture was stirred at 40 ЊC
for 2 h. TLC analysis (33% EtOAc–light petroleum ether)
revealed a completed conversion, after which the mixture was
concentrated and purified by silica gel chromatography (20%
EtOAc–light petroleum ether) to give a colourless syrup of 42
(185 mg, 0.28 mmol, 80%); δH (300 MHz; CDCl3; Me4Si) 7.16–
7.31 (m, 20H, CHarom), 5.76–5.86 (m, 2H, H-9Ј,10Ј), 4.88 (br s,
2H, CH2 Bn), 4.51, 4.54, 4.60, 4.67, 4.84 and 4.89 (6d, each 1H,
CH2 Bn), 4.14 (d, 1H, J 4.9 and 14.7 Hz, H-8Ј), 4.04 (t, 1H,
J 9.2 Hz, H-3), 3.84–4.01 (m, 1H, H-8Ј), 3.57–3.76 (m, 5H,
H-1,4,5 and 2 × H-6), 3.33 (d, 1H, J 9.5 Hz, H-2), 2.61–2.69
(m, 1H, H-11Ј), 2.11–2.33 (m, 3H, H-4Ј,5Ј,11Ј), 1.42–1.83 (m,
2H, H-4Ј,5Ј); δC (50 MHz; CDCl3; Me4Si) 137.9, 138.1,
138.2 and 138.6 (Cq Bn), 131.7 and 131.9 (C-9Ј,10Ј), 127.4–
128.8 (CHarom), 98.6 (C-1), 73.2, 74.9 and 75.4 (CH2 Bn), 70.7,
73.4, 78.6, 81.0, 83.3 and 83.7 (C-1Ј,2,3,4,5,6Ј), 68.9 (C-6), 67.1
(C-8Ј), 34.3 (C-11Ј), 27.5 (C-4Ј), 24.8 (C-5Ј); MS (ESI): calc. for
C42H46O7 662.3, found m/z 685.3 (M ϩ Na)ϩ.
(2R,3R,4S,5R,6S )-3,4,5-Tris-benzyloxy-2-benzyloxymethyl-
1,7-dioxa-spiro[5.5]undec-8-ene (38). To a stirred solution of 8
(330 mg, 0.56 mmol) in anhydrous ethanol (30 mL) were added
Wilkinson’s catalyst (129 mg, 0.13 mmol) and DBU (2 drops)
under a nitrogen atmosphere. The mixture was heated to 60 ЊC
for 1 h after which TLC analysis (25% EtOAc–light petroleum
ether) revealed completed conversion. The mixture was allowed
to cool to room temperature and concentrated. Silica gel chrom-
atography (15% EtOAc–light petroleum ether) of the residue
yielded 38 as a colourless syrup (296 mg, 0.50 mmol, 90%);
[α]Dϩ8.4 (c 1 in CHCl3); δH (200 MHz; CDCl3; Me4Si) 7.16–
7.26 (m, 20H, CHarom), 6.25 (d, 1H, J 6.2 Hz, H-8), 4.50, 4.55,
4.57, 4.60, 4.68 4.86, 4.91 and 4.92 (8d, each 1H, CH2 Bn), 4.79
(m, 1H, H-9), 4.16 (t, 1H, J 9.1 Hz, H-4), 4.11–4.21 (m, 1H,
CH2OBn), 3.62–3.79 (m, 3H, H-2,3 and CH2OBn), 3.40 (d, 1H,
J 9.9 Hz, H-5), 1.49–2.05 (m, 4H, 2 × H-10 and 2 × H-11);
δC (50 MHz; CDCl3; Me4Si) δ 139.6 (C-8), 137.7, 138.2 and
138.6 (Cq Bn), 127.5–128.4 (CHarom), 102.3 (C-9), 97.6 (C-6),
71.8, 78.3, 82.6 and 83.0 (C-2,3,4,5), 73.1, 74.8, 75.5 and 75.6
(CH2 Bn), 68.4 (CH2OBn), 26.8 (C-11), 16.0 (C-10); MS (ESI):
calc. for C38H40O6 592.3, found m/z 615.3 (M ϩ Na)ϩ.
Acknowledgements
(2R,3R,4S,5R,6S,8R,9S )-8-Allyl-3,4,5-tris-benzyloxy-2-
benzyloxymethyl-1,7-dioxa-spiro[5.5]-undecan-9-ol (39). To a
chilled (0 ЊC) solution of spiroketal 38 (370 mg, 0.63 mmol) in
anhydrous dichloromethane (3 mL) was added dropwise a
freshly prepared solution of 3,3-dimethyldioxirane (9 mL,
0.09 M, 0.8 mmol) in acetone.25 After stirring the mixture for
The authors thank Fons Lefeber for recording the nOe-differ-
ence spectra, and Hans van den Elst and Nico Meeuwenoord
for recording the mass spectra. H.S.O. thanks the Netherlands
Organization for Scientific Research (NWO) for financial
support.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2, 1 3 9 5 – 1 4 0 3
1402

View Article Online
12 H. Kuzuhara and H. G. Fletcher, J. Am. Chem. Soc., 1967, 73, 2531.
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