Total synthesis of a protected form of sphingofungin e using the [3,3]-sigmatropic rearrangement of an allylic thiocyanate as the key reaction

Article abstract of DOI:10.1016/j.carres.2010.09.016

An approach to the stereocontrolled synthesis of the protected form of sphingofungin E (32) starting from the known protected d-glucose derivative 3 is described herein. For the construction of a tetrasubstituted carbon atom that is substituted with nitro

Full text of DOI:10.1016/j.carres.2010.09.016

Carbohydrate Research 345 (2010) 2427–2437
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Total synthesis of a protected form of sphingofungin E using the
[3,3]-sigmatropic rearrangement of an allylic thiocyanate as the key reaction
Miroslava Martinková a, , Jozef Gonda a, Jana Špaková Raschmanová a, Michaela Slaninková a, Juraj Kuchár b
⇑
a Institute of Chemical Sciences, Department of Organic Chemistry, P. J. Šafárik University, Moyzesova 11, Sk-040 01 Košice, Slovak Republic
b Institute of Chemical Sciences, Department of Inorganic Chemistry, P. J. Šafárik University, Moyzesova 11, Sk-040 01 Košice, Slovak Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 June 2010
Received in revised form 8 September 2010
Accepted 13 September 2010
Available online 17 September 2010
An approach to the stereocontrolled synthesis of the protected form of sphingofungin E (32) starting from
the known protected D-glucose derivative 3 is described herein. For the construction of a tetrasubstituted
carbon atom that is substituted with nitrogen, the [3,3]-sigmatropic rearrangement of thiocyanate 8 was
employed. Subsequent functional group interconversions afforded the highly functionalized fragment,
allylic bromide 26. Its coupling reaction with the known C12 hydrophobic segment 2, followed by further
manipulation, completed the total synthesis.
Keywords:
Ó 2010 Elsevier Ltd. All rights reserved.
Sphingofungin E
Aza-Claisen rearrangement
Isothiocyanates
1. Introduction
OH OH
Sphingofungin E (1) is a complex amino acid natural product
that was reported in 1992 by a group at Merck. The compound
was isolated from the fermentation broth of Paecilomyces variotii
together with sphingofungin F.1 Both compounds are reported to
be inhibitors2 of serine palmitoyltransferase (SPT),3,4 an essential
enzyme involved in the first step of sphingolipid biosynthesis, with
antifungal activity against several human pathogenic fungi.1 From
a structural standpoint, sphingofungin E (1) (Scheme 1) possesses
HO2C
H2N
OH
O
HO
1
sphingofungin E
Bn
N
O
R
OBn
O
O
O
PhO2S
+
Br
O
O
an intriguing
a-substituted a
-amino acid motif5 connected with
26e
26
: R = CH2OTBDMS
trihydroxylated alkyl chain. Its significant biological properties,
as well as the above-mentioned structural features, had made
sphingofungin E an attractive target for synthetic chemists and
four total syntheses of 1 have been developed.6 Generally, the
strategies used in these works6 are organised into three parts:
the construction of the side chain segment with a keto group at
C-14, the preparation of the polar head group bearing four stereo-
genic centres and the cross-coupling reaction of these two frag-
Ac
N
O
SCN
O
TBDMSO
O
O
O
O
H
H
O
O
AcO
TBDMSO
HO
HO
10
8
O
ments. For the stereoselective introduction of
stereocentre, Chida‘s group employed the Overman rearrangement
of allylic trichloroacetimidates derived from
-glucose,6e,f while
Nakamura and Shiozaki6c,d used the condensation of a 2-ulose pre-
a quaternary
O
H
O
TBDMSO
D
3
pared from a protected D-glucose derivative with dichloromethylli-
Scheme 1. Retrosynthetic route to sphingofungin E (1).
thium followed by treatment with NaN3. Trost and Lee6b installed
the tetrasubstituted carbon by Pd-catalysed asymmetric alkylation
of an azlactone prepared from methyl N-benzoylglycine, and Lin
acid, in which the Baylis–Hillman reaction and Hatakeyama‘s
methodology were involved as the key steps for a preparation of
an oxazoline derivative possessing the tetrasubstituted carbon.
In this paper, we would like to describe the total synthesis of
and co-workers6a,g reported the total synthesis of 1 from
L-tartaric
⇑
the protected form of sphingofungin E (32) starting from
D-glucose,
Corresponding author. Tel.: +421 55 2342329; fax: +421 55 6222121.
E-mail address: miroslava.martinkova@upjs.sk (M. Martinková).
which utilised a [3,3]-sigmatropic aza-Claisen rearrangement6e,f,7
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.09.016

2428
M. Martinková et al. / Carbohydrate Research 345 (2010) 2427–2437
of the allylic thiocyanates as one of the fascinating methodologies
for the installment of the tetrasubstituted carbon with nitrogen,
which was developed in our laboratory.8
which was converted into thiocyanate 8 in two reaction steps. It
was shown that O-mesylation of the corresponding alcohol 7, fol-
lowed by treatment with KSCN8b in acetonitrile, confirmed satis-
factory results, and the desired 8 was obtained in 67% yield after
flash chromatography (Scheme 2).
2. Results and discussion
With allylic thiocyanate 8 in hand, we then performed the ther-
mal aza-Claisen rearrangement of 8, which was carried out at 90 °C
in n-heptane under a nitrogen atmosphere and to give the rear-
ranged products 9 and 10 in 72% overall yield, as a barely separable
mixture of diastereoisomers (9:10 = 65:35 ratio, determined by 1H
NMR spectroscopy). On the other hand, the remarkable accelera-
tion of the thermal [3,3]-sigmatropic rearrangement of 8 (from
24 h to 3 h) with satisfactory yield (69%) was observed using sealed
vessel microwave irradiation conditions11 in n-heptane at 90 °C;
however, it had practically no influence on the diastereoselectivity
(9:10 = 70:30, determined by 1H NMR spectroscopy). The stereo-
chemistry of the newly constructed tetrasubstituted carbon was
assigned by transformation of a mixture of isothiocyanates 9 and
10 into cyclic carbamates 13 and 14 by the following sequence of
reaction steps (Scheme 3).
Thus, desilylation of the rearranged products 9 and 10 (ca. 2:1,
prepared from 8) using tetrabutylammonium fluoride in THF gave
the corresponding thiocarbamates 11 in 75% yield. The replace-
ment of the sulfur atom by oxygen was accomplished under very
mild conditions by the action of mesitylnitrile oxide12 (MNO) in
CH3CN to afford carbamates 12 (95%, Scheme 3). Acetylation of a
mixture of the cyclic urethanes 12 with acetic anhydride in
pyridine in the presence of DMAP as a catalyst provided crystalline
diacetates 13 and 14 in 85% yield as a separable mixture of diaste-
reoisomers. Although both compounds 13 and 14 crystallized well
from a mixture of ether and hexane, only acetate 13 afforded single
crystals that upon X-ray diffraction analysis (Fig. 1) clearly showed
that the newly incorporated quaternary centre in 13 possesses the
5S configuration. These results show that the minor stereoisomer
of the rearrangement 10 has the same configuration at C-5
position.
Based on the retrosynthetic analysis illustrated in Scheme 1, our
stereocontrolled approach towards 1 divided this molecule into
two major segments. For the construction of the non-polar side
chain 26e as well as the coupling of this lipophilic part and the
hydrophilic segment 26, we adopted the sulfone-mediated proto-
col reported by Chida and co-workers.6e The C-1–C-8 fragment
26 possessing an (E)-allylic bromide function was prepared from
the highly functionalized cyclic carbamate 13 that contained the
necessary
ous stereogenic centres. The aza-Claisen rearrangement of thiocy-
anate 8, derived from the known9 protected
-glucofuranose 3,
a-substituted serine moiety and the remaining contigu-
a-D
generated a quaternary carbon with the amino function in 13.
2.1. Preparation of the functionalized cyclic carbamate 13
Synthesis of the functionalized part 13 commenced with 3-O-
(tert-butyldimethylsilyl)-1,2-O-isopropylidene-
a
a
-
D
-glucofuranose
39 prepared from 1,2:5,6-di-O-isopropylidene-
-D-glucofuranose
in two steps: (i) the 3-O-silylation with TBDMSCl/imidazole in
DMF at 70 °C (85.5%); (ii) the selective removal of the 5,6-O-isopro-
pylidene group with 4:1 CH3CO2H–H2O (40 °C, 80%). The primary
alcohol function in the resulting diol 3 was selectively silylated
(TBDMSCl, Et3N, DMAP and CH2Cl2) to afford 4 in 92% yield
(Scheme 2). Its oxidation with IBX10 in acetonitrile gave 5-ulose
5 (97%), which was subsequently treated with the stabilized ylide
(Ph3P@CHCO2CH3, toluene, reflux) to afford (Z)-a,b-unsaturated
ester 6 exclusively in 97% yield (Scheme 2).
Its structure was determined by 1H and 13C NMR spectroscopy,
including NOE experiments. Reduction of 6 using the standard pro-
cedure with LiAlH4 resulted in allylic alcohol 7 (81%, Scheme 2),
O
2.2. Synthesis of the key alcohol 25
HO
TBDMSO
O
O
O
O
HO
Having revealed the structure of the highly functionalized
fragment 13, our strategy employed in the synthesis of C-1–C-8
fragment 26 was achieved by a series of functional group manipu-
lations. In order to obtain the key allylic alcohol 25, deprotection of
the acetyl groups in 13 was realised under basic conditions (K2CO3,
CH3OH) and afforded product 12S in 95% yield (Scheme 4).
Exposure of 12S to benzyl bromide in dry DMF using sodium
hydride and catalytic amounts of tetrabutylammonium iodide pro-
duced the completely protected derivative 15 (96%, Scheme 4).
c
H
a, b
H
O
O
TBDMSO
TBDMSO
3
5
CO2CH3
OH
O
TBDMSO
TBDMSO
O
O
O
d
H
H
O
O
TBDMSO
TBDMSO
6
7
SCN
O
H
N
H
N
S
O
TBDMSO
f
O
O
e
9
O
a
O
b
O
O
O
H
+
H
H
HO
10
O
TBDMSO
O
O
HO
8
12
11
SCN
SCN
TBDMSO
TBDMSO
Ac
O
Ac
O
O
O
O
8
O
O
7
N
N
5
H
H
+
O
c
O
4
1
O
O
O
O
O
TBDMSO
TBDMSO
+
3
2
6
H
AcO
H
9
10
O
O
AcO
13
14
Scheme 2. Reagents and conditions: (a) TBDMSCl, Et3N, DMAP, CH2Cl2, rt, 4, 92%;
(b) IBX, CH3CN, reflux, 97%; (c) Ph3P@CHCO2CH3, toluene, reflux, 97%; (d) LiAlH4,
Et2O, 0 °C?rt, 81%; (e) (i) MsCl, Et3N, CH2Cl2, 0 °C?rt; (ii) KSCN, CH3CN, rt, 67%; (f)
(i) n-heptane, 90 °C, 24 h, 72% or (ii) MW, n-heptane, 90 °C, 3 h, 69%.
Scheme 3. Reagents and conditions: (a) TBAF, THF, 0 °C?rt, 75%; (b) MNO, CH3CN,
rt, 95%; (c) Ac2O, Py, DMAP, rt, 85%.

M. Martinková et al. / Carbohydrate Research 345 (2010) 2427–2437
2429
The observed coupling constant in 20 (J = 15.7 Hz) proved the
trans-configuration of the double bond. The treatment of 20 with
2,2-dimethoxypropane13 and catalytic amounts of CSA resulted
in the formation of the corresponding isopropylidene derivative
21 in 81% yield (Scheme 4). Cleavage of the acetate in 21 was
achieved by employing sodium ethoxide in ethanol to give alcohol
22 (92%, Scheme 4). The recovered hydroxyl group in 22 was pro-
tected as its tert-butyldimethylsilyl ether 23 (94%, Scheme 4) using
TBDMSOTf and 2,6-lutidine in dichloromethane. Reduction of the
unsaturated ester 23 with DIBAL-H in CH2Cl2 at ꢀ78 °C afforded
the allylic alcohol 25 (51%), together with the
a,b-unsaturated
aldehyde 24 (35%), which was immediately reduced with NaBH4
to furnish 25 in 94% yield.
2.3. Coupling reaction and completion of the synthesis of 32
Alcohol 25 was subsequently transformed into the fully pro-
tected bromide 26 in 85.5% yield by a two-step sequence of func-
tional group manipulations: (i) the mesylation of the resulting
allylic alcohol 25 with MsCl/Et3N in CH2Cl2; and (ii) the displace-
ment of the O-mesyl group by treatment with LiBr6e (Scheme 5).
As was mentioned above, based on the retrosynthetic analysis
(Scheme 1), we adopted the reported sulfone-mediated coupling
reaction, which has been used for the total synthesis of both myr-
iocin and sphingofungin E by Chida and co-workers.6e,f
Figure 1. ORTEP structure of 13 showing the crystallographic numbering.
Ac
N
Bn
N
O
O
O
O
O
O
O
a
O
b
H
H
O
O
AcO
BnO
Sulfone 2,6e after reaction with n-BuLi at ꢀ78 °C in THF, was
then treated with the bromide 26 to generate the product 27 as a
mixture of inseparable diastereoisomers on silica gel (ꢁ1:0.7 ratio,
determined by 1H NMR spectroscopy) in 95% yield (Scheme 5).
Since the attempted desulfonation of 27 by either aluminum amal-
gam14 or Li-naphthalene6e,15 afforded unidentified products, we
decided to search for more effective reaction conditions. In the
end, desulfonation of 27 was achieved using 6% sodium amalgam16
in dry methanol and resulted in the formation of the fully pro-
tected aminopolyol 28 (64%). After routine deprotection of 28 with
TBAF, the resulting alcohol 29 (88%) was subsequently treated with
15
13
Bn
Bn
N
O
O
OAc
CHO
N
O
O
O
O
O
e
c, d
OH
H
H
O
OH
BnO
BnO
16
19
O
O
O
O
Bn
N
Bn
OAc
OBn
OAc
OBn
g
f
COOEt
N
COOEt
PDC in DMF to furnish the desired a-substituted a-amino acid 30
O
O
OH OH
(65%) that possessed the correct stereochemistry at all stereogenic
centres (Scheme 5). Finally, deprotection of both the ethylene ketal
and the 1,3-O-isopropylidene groups in 30 by acid hydrolysis (2 M
aq HCl) provided d-lactone 31 in 72% yield. Treatment of 31 with
10% aq sodium hydroxide in methanol and subsequent neutralisa-
tion with Amberlite IR 120 H+ furnished 32 (81%, Scheme 5) as the
protected form of sphingofungin E (1).
21
20
O
Bn
O
Bn
N
OTBDMS
OTBDMS
OBn
h
N
OBn
O
O
O
COOEt
OH
+
24
O
O
O
k
23
25
3. Conclusions
Scheme 4. Reagents and conditions: (a) (i) K2CO3, CH3OH, rt, 12S, 95%; (ii) NaH,
BnBr, TBAI, DMF, rt, 96%, (b) O3, CH3OH, ꢀ78 °C, Ph3P, CH2Cl2, rt, 89%; (c) (i) NaBH4,
CH3OH, 0 °C?rt, 17, 95%; (ii) Ac2O, DMAP, py, rt, 18, 94%; (d) 8:2 TFA–H2O, rt, 94%;
(e) Ph3P@CHCO2Et, PhCO2H, CH2Cl2, rt, 91%; (f) 2,2-DMP, CSA, rt, 81%; (g) (i) EtONa,
EtOH, 0 °C, 22, 92%; (ii) TBDMSOTf, 2,6-lutidine, CH2Cl2, 0 °C?rt, 94%; (h) (i) DIBAl-
H, CH2Cl2, ꢀ78 °C, 24, 35%, 25, 51%; (k) NaBH4, CH3OH, 0 °C?rt, 94%.
In conclusion, the total synthesis of the protected form of
sphingofungin E (32) has been accomplished starting from the
known a-D-glucofuranose 3. This work demonstrates that our de-
scribed methodology using an aza-Claisen rearrangement of the
allylic thiocyanates derived from various sugar molecules has more
general utility, and from this viewpoint it appeared particularly
interesting to apply this above-mentioned strategy for the con-
Ozonolysis of 15, followed by PPh3 treatment, successfully pro-
vided corresponding aldehyde 16 (89%), which was immediately
reduced with NaBH4 in methanol to give alcohol 17 in 95% yield
(Scheme 4). The primary hydroxyl group present in 17 was pro-
tected as the acetate using acetic anhydride, dry pyridine and
DMAP as a catalyst to produce 18 in 94% isolated yield. Exposure
of compound 18 to trifluoroacetic acid resulted in the cleavage of
the 1,2-O-isopropylidene group, and the corresponding lactol 19
was isolated as an inseparable mixture of anomers. Homologation
of the resulting furanose 19 via a Wittig reaction (Ph3P@CHCO2Et,
struction of other natural products containing the
a-substituted
a-amino acid motif. Further studies towards the total synthesis
of such compounds are in progress in our laboratory.
4. Experimental
4.1. General methods
CH2Cl2) afforded (E)-a,b-unsaturated ester 20 as the sole product
All commercial reagents were used in the highest available pur-
ity from Aldrich, Fluka, E. Merck or Acros Organics without further
purification. Solvents were dried and purified before use according
in 91% yield (Scheme 4). This product after flash chromatography
and a rapid 1H NMR analysis was immediately used in the next
reaction.

2430
M. Martinková et al. / Carbohydrate Research 345 (2010) 2427–2437
O
O
Bn
N
O
O
Bn
N
OTBDMS
OBn
OTBDMS
OBn
O
O
a
b
c
25
Br
O
O
SO2Ph
O
O
26
27
O
Bn
N
Bn
N
OTBDMS
OBn
COOH
O
OBn
O
O
O
O
d
O
O
O
O
O
O
28
31
30
32
OH
O
OH OH
O
f
O
O
e
O
N
Bn
N
Bn
O
O
OBn
OBn
CO2H
O
Scheme 5. Reagent and conditions: (a) (i) MsCl, Et3N, CH2Cl2, 0 °C?rt; (ii) LiBr, THF, rt, 85.5%; (b) 2,6e BuLi, ꢀ78 °C, 95%; (c) 6% Na/Hg, CH3OH, Na2HPO4, 0 °C?rt, 64%; (d) (i)
TBAF, THF, 0 °C?rt, 29, 88%; (ii) PDC, DMF, rt, 65%; (e) 2 M aq HCl, THF, reflux, 72%; (f) 10% aq NaOH, CH3OH, 80 °C, 81%.
to standard procedures. For flash column chromatography on silica
gel, Kieselgel 60 (0.040–0.063 mm, 230–400 mesh, E. Merck) was
used. Solvents for flash chromatography (hexane, ethyl acetate,
MeOH, dichloromethane) were distilled before using. Thin-layer
chromatography was run on E. Merck Silica Gel 60 F254 analytical
plates; detection was carried out with either ultraviolet light
(254 nm), or by spraying with a solution of phosphomolybdic acid,
potassium permanganate basic solution, a solution of concentrated
H2SO4 with subsequent heating. 1H NMR and 13C NMR spectra
were recorded in CDCl3 and CD3OD (the deuterium content of used
solvents lay between 98% and 99%) at ambient temperature on a
Varian Mercury Plus 400 FT NMR (400.13 MHz for 1H and
100.6 MHz for 13C) or on a Varian Premium COMPACT 600
(599.87 MHz for 1H and 150.84 MHz for 13C) spectrometers using
TMS as internal reference. For 1H d are given in parts per million
(ppm) relative to TMS (d = 0.0) and for 13C relative to CDCl3
(d = 77.0) or CD3OD (d = 49.05). The multiplicity of the 13C NMR sig-
nals concerning the 13C–1H coupling was determined by the DEPT
method. Chemical shifts (in ppm) and coupling constants (in Hz)
were obtained by first-order analysis; assignments were derived
from COSY and H/C correlation spectra. Infrared (IR) spectra were
measured with a Nicolet Avatar 330 FTIR spectrometer as KBr pel-
added at room temperature. The resulting mixture was stirred
for 20 h at the same temperature and then poured into 1 M aq
KHSO4 solution (183 mL). The organic layer was washed with brine
(90 mL), dried over Na2SO4 and concentrated under reduced pres-
sure. The residue was purified by column chromatography on silica
gel (15:1 hexane–EtOAc) to afford 21.7 g (92%) of crystalline prod-
uct 4: mp 56–57 °C; ½a D20
ꢂ
ꢀ104.1 (c 0.27, CHCl3). 1H NMR (CDCl3,
400 MHz): d 0.08 (s, 6H, 2 ꢃ CH3), 0.14 (s, 3H, CH3), 0.15 (s, 3H,
CH3), 0.90 (s, 9H, 3 ꢃ CH3), 0.91 (s, 9H, 3 ꢃ CH3), 1.31 (s, 3H,
CH3), 1.47 (s, 3H, CH3), 2.52 (d, J5,OH = 6.2 Hz, 1H, OH), 3.74 (dd,
J6,6 = 10.7 Hz, J6,5 = 5.7 Hz, 1H, H-6), 3.81–3.86 (m, 2H, H-6, H-5),
4.02 (dd, J5,4 = 8.5 Hz, J4,3 = 2.6 Hz, 1H, H-4), 4.30 (d, J4,3 = 2.6 Hz,
1H, H-3), 4.35 (d, J2,1 = 3.6 Hz, 1H, H-2), 5.87 (d, J2,1 = 3.6 Hz, 1H,
H-1). 13C NMR (CDCl3, 100 MHz): d ꢀ5.4 (CH3), ꢀ5.4 (CH3), ꢀ5.2
(CH3), ꢀ4.9 (CH3), 18.1 (C), 18.3 (C), 25.7 (3 ꢃ CH3), 25.9
(3 ꢃ CH3), 26.4 (CH3), 26.8 (CH3), 64.4 (CH2), 68.0 (CH), 75.5 (CH),
80.2 (CH), 85.4 (CH), 105.1 (CH), 111.7 (C). Anal. Calcd for
C21H44O6Si2: C, 56.21; H, 9.88. Found: C, 56.15; H, 9.95.
4.3. 3,6-Bis(O-tert-butyldimethylsilyl)-1,2-O-isopropylidene-
a-
D-xylo-hexofuranos-5-ulose (5)
lets and expressed in
m
values (cmꢀ1). Optical rotations were mea-
D (c
To a solution of alcohol 4 (21.7 g, 48.36 mmol) in CH3CN
sured on a P3002 Krüss polarimeter and reported as follows: [
a]
(422 mL) was added o-iodoxybenzoic acid (27.08 g, 96.7 mmol),
and the resulting mixture was stirred for 2 h at reflux. After the
starting material was completely consumed (judged by TLC), the
reaction was stopped and allowed to cool to room temperature.
The insoluble materials were removed by filtration, the solvent
was evaporated under reduced pressure, and the residue was puri-
fied by column chromatography on silica gel (17:1 hexane–EtOAc)
in grams per 100 mL, solvent). Melting points were recorded on a
Kofler hot block, and are uncorrected. Microwave reactions were
carried out in a focused microwave system (CEM Discover). The
temperature content of the vessel was monitored using a cali-
brated infrared sensor mounted under the vessel. At the end of
all reactions, the contents of vessel were cooled rapidly using a
stream of compressed air. Small quantities of reagents (
lL) were
to give 20.95 g (97%) of crystalline ketone 5: mp 65–67 °C; ½a D20
ꢂ
measured with appropriate syringes (Hamilton). All reactions were
performed under an atmosphere of nitrogen unless otherwise
noted.
ꢀ123.3 (c 0.30, CHCl3). 1H NMR (CDCl3, 400 MHz): d 0.04 (s, 3H,
CH3), 0.05 (s, 3H, CH3), 0.07 (s, 3H, CH3), 0.09 (s, 3H, CH3), 0.84
(s, 9H, 3 ꢃ CH3), 0.90 (s, 9H, 3 ꢃ CH3), 1.32 (s, 3H, CH3), 1.46 (s,
3H, CH3), 4.35 (d, J2,1 = 3.5 Hz, 1H, H-2), 4.48 (m, 2H, 2 ꢃ H-6),
4.55 (d, J4,3 = 3.1 Hz, 1H, H-3), 4.78 (d, J4,3 = 3.1 Hz, 1H, H-4), 6.02
(d, J2,1 = 3.5 Hz, 1H, H-1). 13C NMR (CDCl3, 100 MHz): d ꢀ5.5
(CH3), ꢀ5.4 (CH3), ꢀ5.3 (CH3), ꢀ4.9 (CH3), 17.9 (C), 18.3 (C), 25.6
(3 ꢃ CH3), 25.8 (3 ꢃ CH3), 26.4 (CH3), 27.0 (CH3), 68.7 (CH2), 77.5
(CH), 84.9 (CH), 85.7 (CH), 105.7 (CH), 112.4 (C), 205.3 (C). Anal.
Calcd for C21H42O6Si2: C, 56.46; H, 9.48. Found: C, 56.55; H, 9.41.
4.2. 3,6-Bis(O-tert-butyldimethylsilyl)-1,2-O-isopropylidene-
-glucofuranose (4)
a-
D
To a solution of known 39 (17.58 g, 52.56 mmol) in dry CH2Cl2
(272 mL) Et3N (8.89 mL, 63.26 mmol), DMAP (0.91 g, 7.45 mmol)
and tert-butyldimethylsilyl chloride (9.06 g, 60.11 mmol) were

M. Martinková et al. / Carbohydrate Research 345 (2010) 2427–2437
2431
4.4. 3,6-Bis(O-tert-butyldimethylsilyl)-5-C-(Z)-carbomethoxy-
methylene-5-deoxy-1,2-O-isopropylidene- -glucofuranose (6)
oil: ½a 2D0
ꢂ
+110.9 (c 0.24, CHCl3). 1H NMR (CDCl3, 400 MHz): d 0.03
a
-D
(s, 3H, CH3), 0.07 (s, 3H, CH3), 0.07 (s, 3H, CH3), 0.09 (s, 3H, CH3),
0.87 (s, 9H, 3 ꢃ CH3), 0.91 (s, 9H, 3 ꢃ CH3), 1.33 (s, 3H, CH3), 1.50
(s, 3H, CH3), 3.67 (dd, J8,8 = 12.6 Hz, J8,7 = 7.8 Hz, 1H, H-8), 4.06
(dd, J8,8 = 12.6 Hz, J8,7 = 8.8 Hz, 1H, H-8), 4.17 (m, 2H, 2 ꢃ H-6),
4.19 (d, J4,3 = 2.7 Hz, 1H, H-3), 4.38 (d, J2,1 = 3.7 Hz, 1H, H-2), 4.85
(d, J4,3 = 2.7 Hz, 1H, H-4), 5.86 (m, 1H, H-7), 5.93 (d, J2,1 = 3.7 Hz,
1H, H-1). 13C NMR (CDCl3, 100 MHz): d ꢀ5.4 (CH3), ꢀ5.4 (CH3),
ꢀ4.9 (CH3), ꢀ4.7 (CH3), 18.1 (C), 18.3 (C), 25.8 (3 ꢃ CH3), 25.9
(3 ꢃ CH3), 26.3 (CH3), 26.8 (CH3), 31.9 (CH2), 64.8 (CH2), 77.9
(CH), 80.1 (CH), 85.2 (CH), 104.1 (CH), 111.8 (C), 112.9 (SCN),
120.0 (CH), 139.9 (C). Anal. Calcd for C24H45NO5SSi2: C, 55.88; H,
8.79; N, 2.72. Found: C, 55.85; H, 8.71; N, 2.75.
To a solution of ketone 5 (20.95 g, 46.89 mmol) in dry toluene
(490 mL) was added the stabilized ylide Ph3P@CHCO2CH3
(39.18 g, 117.2 mmol) and the resulting mixture was stirred at re-
flux. After 17 h, the reaction mixture did not contain any ketone 5,
the solvent was evaporated under reduced pressure and the resi-
due was purified by column chromatography on silica gel (20:1
hexane–EtOAc) to afford 22.87 g (97%) of
a
,b-unsaturated ester 6
as a colourless oil: ½a D20
ꢂ
+125.8 (c 0.24, CHCl3). 1H NMR (CDCl3,
400 MHz): d ꢀ0.06 (s, 3H, CH3), 0.04 (s, 3H, CH3), 0.06 (s, 6H,
2 ꢃ CH3), 0.84 (s, 9H, 3 ꢃ CH3), 0.91 (s, 9H, 3 ꢃ CH3), 1.33 (s, 3H,
CH3), 1.52 (s, 3H, CH3), 3.70 (s, 3H, OCH3), 4.35 (d, J2,1 = 3.7 Hz,
1H, H-2), 4.40–4.48 (m, 2H, 2 ꢃ H-6), 4.67 (d, J4,3 = 3.0 Hz, 1H,
H-3), 5.82 (m, 1H, H-4), 5.93 (d, J2,1 = 3.7 Hz, 1H, H-1), 6.14 (dd,
J7,6 = 3.9 Hz, J7,6 = 2.2 Hz, 1H, H-7). 13C NMR (CDCl3, 100 MHz):
d ꢀ5.5 (CH3), ꢀ5.5 (CH3), ꢀ5.3 (CH3), ꢀ5.1 (CH3), 17.9 (C), 18.2
(C), 25.7 (3 ꢃ CH3), 25.8 (3 ꢃ CH3), 26.6 (CH3), 27.1 (CH3), 51.1
(CH3), 63.2 (CH2), 77.7 (CH), 80.9 (CH), 85.6 (CH), 104.9 (CH),
111.9 (C), 112.5 (CH), 159.2 (C), 166.7 (C). Anal. Calcd for
4.7. A mixture of 3,6-bis(O-tert-butyldimethylsilyl)-5-deoxy-1,2-
O-isopropylidene-5-isothiocyanato-5-C-vinyl-
(9) and 3,6-bis(O-tert-butyldimethylsilyl)-5-deoxy-1,2-O-isopro-
pylidene-5-isothiocyanato-5-C-vinyl-b-L-idofuranose (10)
a-D-glucofuranose
4.7.1. Microwave-assisted synthesis
C24H46O7Si2: C, 57.33; H, 9.22. Found: C, 57.25; H, 9.31.
Thiocyanate 8 (0.10 g, 0.194 mmol) was weighed in a 10-mL
glass pressure microwave tube equipped with a magnetic stirbar.
Heptane (3.6 mL) was added, the tube was closed with a silicone
septum and the reaction mixture was subjected to microwave irra-
diation for 3 h at 90 °C. Evaporation of the solvent and chromatog-
raphy on silica gel (35:1 hexane–EtOAc) gave 69 mg (69%) of a
mixture of diastereoisomeric isothiocyanates 9 and 10 as colour-
less oils.
4.5. 3,6-Bis(O-tert-butyldimethylsilyl)-5-deoxy-5-C-(Z)-(2-hy-
droxyethylidene)-1,2-O-isopropylidene- -glucofuranose (7)
a-D
Lithium aluminum hydride (4.31 g, 113.6 mmol) was added
portionwise to a solution of ester 6 (22.87 g, 45.48 mmol) in dry
Et2O (280 mL) pre-cooled to 0 °C. The reaction mixture was stirred
for a further 15 min at 0 °C and then for 2 h at room temperature.
The stirring solution was then quenched by dropwise addition of
water (45 mL), and the salts were removed by filtration and
washed with Et2O. The resulting filtrate was dried over Na2SO4,
the solvent was evaporated in vacuo and the residue was purified
on silica gel (7:1 hexane–EtOAc) to give 17.49 g (81%) of alcohol 7
4.7.2. Conventional method
A solution of thiocyanate 8 (12.73 g, 24.68 mmol) in heptane
(60 mL) was heated at 90 °C for 24 h. Evaporation of the solvent
and chromatography on silica gel (35:1 hexane–EtOAc) afforded
9.17 g (72%) of a mixture of isothiocyanates 9 and 10 as colourless
oils.
as a colourless oil: ½a D20
ꢂ
+107.8 (c 0.25, CHCl3). 1H NMR (CDCl3,
400 MHz): d 0.02 (s, 3H, CH3), 0.06 (s, 6H, 2 ꢃ CH3), 0.08 (s, 3H,
CH3), 0.87 (s, 9H, 3 ꢃ CH3), 0.91 (s, 9H, 3 ꢃ CH3), 1.33 (s, 3H,
CH3), 1.50 (s, 3H, CH3), 4.13–4.29 (m, 5H, H-3, 2 ꢃ H-6, 2 ꢃ H-8),
4.38 (d, J2,1 = 3.7 Hz, 1H, H-2), 4.92 (d, J4,3 = 2.5 Hz, 1H, H-4), 5.96
(m, 2H, H-1, H-7). 13C NMR (CDCl3, 100 MHz): d ꢀ5.4 (CH3), ꢀ5.4
(CH3), ꢀ5.0 (CH3), ꢀ4.8 (CH3), 18.1 (C), 18.3 (C), 25.7 (3 ꢃ CH3),
25.9 (3 ꢃ CH3), 26.3 (CH3), 26.8 (CH3), 58.6 (CH2), 64.7 (CH2),
77.9 (CH), 80.3 (CH), 85.4 (CH), 104.2 (CH), 111.7 (C), 126.3 (CH),
136.4 (C). Anal. Calcd for C23H46O6Si2: C, 58.18; H, 9.77. Found: C,
58.09; H, 9.81.
A small amount of the mixture of isothiocyanates was separated
by column chromatography on silica gel (35:1 hexane–EtOAc) to
afford each diastereoisomer in pure form and for use as analytical
samples.
Diastereoisomer 9: Rf 0.37 (35:1 hexane–EtOAc); ½a D20
ꢀ118.6 (c
ꢂ
0.29, CHCl3). 1H NMR (CDCl3, 400 MHz): d 0.09 (s, 3H, CH3), 0.11 (s,
3H, CH3), 0.11 (s, 3H, CH3), 0.16 (s, 3H, CH3), 0.89 (s, 9H, 3 ꢃ CH3),
0.92 (s, 9H, 3 ꢃ CH3), 1.32 (s, 3H, CH3), 1.49 (s, 3H, CH3), 3.46 (d,
J6,6 = 10.0 Hz, 1H, H-6), 3.79 (d, J6,6 = 10.0 Hz, 1H, H-6), 4.31 (d,
J2,1 = 3.5 Hz, 1H, H-2), 4.35 (d, J4,3 = 2.7 Hz, 1H, H-3), 4.52 (d,
J4,3 = 2.7 Hz, 1H, H-4), 5.17 (d, J8cis,7 = 10.7 Hz, 1H, H-8cis), 5.35 (d,
J8trans,7 = 17.2 Hz, 1H, H-8trans), 5.91 (d, J2,1 = 3.5 Hz, 1H, H-1), 6.03
(dd, J8trans,7 = 17.2 Hz, J8cis,7 = 10.7 Hz, 1H, H-7). 13C NMR (CDCl3,
100 MHz): d ꢀ5.5 (CH3), ꢀ5.4 (CH3), ꢀ5.0 (CH3), ꢀ4.6 (CH3), 18.0
(C), 18.2 (C), 25.8 (3 ꢃ CH3), 25.9 (3 ꢃ CH3), 26.5 (CH3), 27.0
(CH3), 68.4 (C), 68.4 (CH2), 76.1 (CH), 79.5 (CH), 85.6 (CH), 105.0
(CH), 112.1 (C), 115.3 (CH2), 134.0 (CH), 136.4 (C). Anal. Calcd for
C24H45NO5SSi2: C, 55.88; H, 8.79; N, 2.72. Found: C, 55.93; H,
8.83; N, 2.68.
4.6. 3,6-Bis(O-tert-butyldimethylsilyl)-5-deoxy-1,2-O-isoprop-
ylidene-5-C-(Z)-(2-thiocyanatoethylidene)-a-D-glucofuranose(8)
Et3N (10.4 mL, 74.0 mmol) was added to a solution of alcohol 7
(17.49 g, 36.84 mmol) in dry CH2Cl2 (273 mL) pre-cooled to 0 °C
and methanesulfonyl chloride (3.42 mL, 44.21 mmol) was then
added dropwise. After stirring at 0 °C for 15 min and then at room
temperature for 45 min, the solvent was removed under reduced
pressure. The residue was diluted with Et2O (100 mL) and the salts
were removed by filtration and washed with Et2O. Evaporation of
the solvent at reduced pressure afforded a crude mesylate that
was used in the subsequent reaction directly without further puri-
fication. To a solution of crude mesylate (20.37 g, 36.84 mmol) in
dry CH3CN (250 mL) was added KSCN (5.37 g, 55.26 mmol). After
stirring for 3 h at room temperature, the solvent was evaporated
under reduced pressure. The residue was diluted with Et2O
(100 mL), the salts were filtered off, the solvent was removed
and the residue was chromatographed on silica gel (17:1 hex-
ane–EtOAc) to yield 12.73 g (67%) of thiocyanate 8 as a colourless
Diastereoisomer 10: Rf 0.33 (hexane–EtOAc 35:1); ½a D20
ꢂ
+59.5 (c
0.60, CHCl3). 1H NMR (C6D6, 400 MHz): d ꢀ0.02 (s, 3H, CH3), 0.01 (s,
3H, CH3), 0.05 (s, 3H, CH3), 0.06 (s, 3H, CH3), 0.92 (s, 9H, 3 ꢃ CH3),
1.00 (s, 9H, 3 ꢃ CH3), 1.09 (s, 3H, CH3), 1.45 (s, 3H, CH3), 3.73 (d,
J6,6 = 8.9 Hz, 1H, H-6), 4.05 (d, J6,6 = 8.9 Hz, 1H, H-6), 4.25 (d,
J4,3 = 3.0 Hz, 1H, H-3), 4.37 (d, J2,1 = 3.6 Hz, 1H, H-2), 4.50 (d,
J4,3 = 3.0 Hz, 1H, H-4), 5.02 (dd, J8cis,7 = 10.6 Hz, J8trans,8cis = 0.9 Hz,
1H, H-8cis), 5.51 (dd, J8trans,7 = 17.1 Hz, J8trans,8cis = 0.9 Hz, 1H, H-
8trans), 5.76 (dd, J8trans,7 = 17.1 Hz, J8cis,7 = 10.6 Hz, 1H, H-7), 5.97
(d, J2,1 = 3.6 Hz, 1H, H-1). 13C NMR (CDCl3, 100 MHz): d ꢀ5.5

2432
M. Martinková et al. / Carbohydrate Research 345 (2010) 2427–2437
(CH3), ꢀ5.5 (CH3), ꢀ4.6 (CH3), ꢀ4.5 (CH3), 17.9 (C), 18.1 (C), 25.8
(3 ꢃ CH3), 25.8 (3 ꢃ CH3), 26.5 (CH3), 27.0 (CH3), 68.4 (CH2), 68.6
(C), 76.2 (CH), 79.7 (CH), 85.5 (CH), 104.5 (CH), 111.9 (C), 117.1
(CH2), 133.6 (CH), 136.7 (C). Anal. Calcd for C24H45NO5SSi2: C,
55.88; H, 8.79; N, 2.72. Found: C, 55.83; H, 8.73; N, 2.78.
hexane–EtOAc) to give 3.02 g (95%) of a mixture of carbamates 12
as a colourless oil.
A small amount of the mixture of carbamates was separated by
column chromatography on silica gel (1:2 hexane–EtOAc) to pro-
vide each diastereoisomer in pure form for use as analytical
samples.
4.8. A mixture of (4S)-4-[(3aR,6S,6aR)-6-hydroxy-2,2-dimethyl-
tetrahydrofuro[2.3-d][1.3]dioxol-5-yl]-4-vinyloxazolidine-2-thione
(4S -11) and (4R)-4-[(3aR,6S,6aR)-6-hydroxy-2,2-dimeth-
yltetrahydrofuro[2.3-d][1.3]dioxol-5-yl]-4-vinyloxazolidine-2-
thione (4R-11)
Diastereoisomer (4S-12): Rf 0.21 (1:2 hexane–EtOAc); mp 142–
143 °C; ½a 2D0
ꢂ
+132.1 (c 0.27, CHCl3). 1H NMR (CDCl3, 400 MHz): d
1.31 (s, 3H, CH3), 1.48 (s, 3H, CH3), 4.06 (d, J4,3 2.8 Hz, 1H, H-4),
4.17 (d, J6,6 8.2 Hz, 1H, H-6), 4.26 (m, 1H, H-3), 4.47 (J3,OH 2.4 Hz,
1H, OH), 4.53 (d, J2,1 3.5 Hz, 1H, H-2), 4.59 (d, J6,6 8.2 Hz, 1H, H-
6), 5.36 (d, J8cis,7 10.7 Hz, 1H, H-8cis), 5.46 (d, J8trans,7 17.3 Hz, 1H,
H-8trans), 5.95 (dd, J8trans,7 17.3 Hz, J8cis,7 10.7 Hz, 1H, H-7), 6.00 (d,
J2,1 3.5 Hz, 1H, H-1), 6.40 (br s, 1H, NH). 13C NMR (CDCl3,
100 MHz): d 26.1 (CH3), 26.8 (CH3), 62.8 (C), 73.9 (CH2), 75.3
(CH), 81.4 (CH), 85.1 (CH), 104.9 (CH), 111.8 (C), 116.6 (CH2),
136.2 (CH), 160.4 (C). Anal. Calcd for C12H17NO6: C, 53.13; H,
4.32; N, 5.16. Found: C, 53.15; H, 4.38; N, 5.12.
To a solution of the mixture of isothiocyanates 9 and 10 (8.07 g,
15.6 mmol) in dry THF (156 mL) were added activated 4 Å pow-
dered molecular sieves (2.88 g). The suspension was treated with
a 1 M solution of Bu4NF (15.6 mL, 15.6 mmol) in THF at 0 °C. The
resulting reaction mixture was stirred for a further 10 min at 0 °C
and then at room temperature for 1 h 20 min. The solid material
was removed by filtration, and washed with tetrahydrofuran, and
the solvent was evaporated. The residue was partitioned between
EtOAc (45 mL) and brine (55 mL), and the water phase was ex-
tracted with further portions of EtOAc (2 ꢃ 40 mL). The combined
organic layers were dried over Na2SO4, the solvent was evaporated
and the residue was chromatographed on silica gel (1:1 hexane–
EtOAc) to afford 3.37 g (75%) of a mixture of thiocarbamates 11
as a colourless oil.
Diastereoisomer (4R-12): Rf 0.16 (hexane–EtOAc, 1:2); ½a D20
ꢂ
ꢀ44.3 (c 0.26, CHCl3). 1H NMR (CDCl3, 400 MHz): d 1.31 (s, 3H,
CH3), 1.49 (s, 3H, CH3), 3.29 (br d, J3,OH 2.5 Hz, 1H, OH), 4.14 (d,
J6,6 9.0 Hz, 1H, H-6), 4.15 (d, J4,3 3.3 Hz, 1H, H-4), 4.31 (m, 1H, H-
3), 4.50 (d, J2,1 3.6 Hz, 1H, H-2), 4.68 (d, J6,6 9.0 Hz, 1H, H-6), 5.34
(d, J8cis,7 10.7 Hz, 1H, H-8cis), 5.45 (d, J8trans,7 17.3 Hz, 1H, H-8trans),
6.01 (d, J2,1 3.6 Hz, 1H, H-1), 6.10 (dd, J8trans,7 17.3 Hz, J8cis,7
10.7 Hz, 1H, H-7), 6.35 (br s, 1H, NH). 13C NMR (CDCl3,
100 MHz): d 26.2 (CH3), 26.8 (CH3), 62.8 (C), 73.0 (CH2), 74.7
(CH), 82.9 (CH), 85.5 (CH), 105.0 (CH), 112.0 (C), 116.2 (CH2),
137.1 (CH), 159.8 (C). Anal. Calcd for C12H17NO6: C, 53.13; H,
4.32; N, 5.16. Found: C, 53.03; H, 4.28; N, 5.20.
A small amount of the mixture of thiocarbamates was separated
by column chromatography on silica gel (1:1 hexane–EtOAc) to
give each diastereoisomer in pure form and for use as analytical
samples.
Diastereoisomer (4S-11): Rf 0.29 (1:1 hexane–EtOAc); ½a D20
ꢂ
+107.4 (c 0.25, CHCl3). 1H NMR (CDCl3, 400 MHz): d 1.32 (s, 3H,
CH3), 1.48 (s, 3H, CH3), 4.14 (d, J4,3 2.8 Hz, 1H, H-4), 4.36 (d, J4,3
2.8 Hz, 1H, H-3), 4.46 (d, J6,6 8.6 Hz, 1H, H-6), 4.61 (d, J2,1 3.4 Hz,
1H, H-2), 4.85 (d, J6,6 8.6 Hz, 1H, H-6), 5.43 (d, J8cis,7 10.7 Hz, 1H,
H-8cis), 5.44 (d, J8trans,7 17.3 Hz, 1H, H-8trans), 5.95 (dd, J8trans,7
17.3 Hz, J8cis,7 10.7 Hz, 1H, H-7), 6.01 (d, J2,1 3.7 Hz, 1H, H-1), 8.00
(br s, 1H, NH). 13C NMR (CDCl3, 100 MHz): d 26.1 (CH3), 26.8
(CH3), 67.3 (C), 75.2 (CH), 78.4 (CH2), 80.2 (CH), 85.2 (CH), 104.9
(CH), 112.1 (C), 117.7 (CH2), 134.9 (CH), 189.9 (C). Anal. Calcd for
C12H17NO5S: C, 50.16; H, 5.96; N, 4.87. Found: C, 50.13; H, 5.98;
N, 4.92.
4.10. (4S)-3-Acetyl-4-[(3aR,6S,6aR)-6-acetoxy-2,2-dimethyltet-
rahydrofuro[2.3-d][1.3]dioxol-5-yl]-4-vinyloxazolidine-2-one
(13) and (4R)-3-acetyl-4-[(3aR,6S,6aR)-6-acetoxy-2,2-dimethyl-
tetrahydrofuro[2.3-d][1.3]dioxol-5-yl]-4-vinyloxazolidine-2-
one (14)
To
a solution of the mixture of carbamates 12 (3.02 g,
11.1 mmol) in pyridine (85 mL) were added DMAP (0.27 g,
2.21 mmol) and Ac2O (3.16 mL, 33.43 mmol) at room temperature.
The resulting reaction mixture was stirred overnight at the same
temperature, then poured into ice water (160 mL) and extracted
with Et2O (3 ꢃ 45 mL). The combined organic layers were dried
over Na2SO4, the solvent was evaporated and the residue was chro-
matographed on silica gel (5:1 hexane–EtOAc) to afford 2.24 g
(57%) of 13 and 1.12 g (28%) of 14 as white crystals.
Diastereoisomer (4R-11): Rf 0.25 (hexane–EtOAc, 1:1); ½a D20
ꢂ
ꢀ47.3 (c 0.37, CHCl3). 1H NMR (CDCl3, 400 MHz): d 1.31 (s, 3H,
CH3), 1.52 (s, 3H, CH3), 4.32 (d, J4,3 3.1 Hz, 1H, H-3), 4.34 (d, J4,3
3.1 Hz, 1H, H-4), 4.41 (d, J6,6 9.4 Hz, 1H, H-6), 4.53 (d, J2,1 3.7 Hz,
1H, H-2), 4.94 (d, J6,6 9.4 Hz, 1H, H-6), 5.40 (d, J8cis,7 10.7 Hz, 1H,
H-8cis), 5.48 (d, J8trans,7 17.3 Hz, 1H, H-8trans), 6.02 (d, J2,1 3.7 Hz,
1H, H-1), 6.05 (dd, J8trans,7 17.3 Hz, J8cis,7 10.7 Hz, 1H, H-7), 8.46
(br s, 1H, NH). 13C NMR (CDCl3, 100 MHz): d 26.2 (CH3), 26.8
(CH3), 67.3 (C), 74.5 (CH), 77.6 (CH2), 82.0 (CH), 85.5 (CH), 105.0
(CH), 112.0 (C), 117.6 (CH2), 135.7 (CH), 188.9 (C). Anal. Calcd for
Diastereoisomer 13: Rf 0.35 (3:1 hexane–EtOAc); mp 128 °C;
½
a D20 +120.0 (c 0.25, CHCl3); IR (KBr) mmax (cmꢀ1) 2991, 1780,
ꢂ
1756, 1707, 1644, 1483, 1374, 1292, 1215. 1H NMR (CDCl3,
400 MHz): d 1.31 (s, 3H, CH3), 1.53 (s, 3H, CH3), 2.10 (s, 3H, CH3CO),
2.48 (s, 3H, CH3CO), 4.06 (d, J6,6 9.3 Hz, 1H, H-6), 4.45 (d, J2,1 3.8 Hz,
1H, H-2), 4.85 (d, J6,6 9.3 Hz, 1H, H-6), 5.13 (d, J4,3 3.2 Hz, 1H, H-4),
5.25 (d, J4,3 3.2 Hz, 1H, H-3), 5.30 (d, J8trans,7 17.4 Hz, 1H, H-8trans),
5.32 (d, J8cis,7 10.8 Hz, 1H, H-8cis), 6.00 (d, J2,1 3.8 Hz, 1H, H-1),
6.14 (dd, J8trans,7 17.4 Hz, J8cis,7 10.8 Hz, 1H, H-7). 13C NMR (CDCl3,
100 MHz): d 20.5 (CH3), 24.6 (CH3), 26.3 (CH3), 26.8 (CH3), 63.4
(C), 69.5 (CH2), 76.6 (CH), 79.1 (CH), 83.5 (CH), 105.1 (CH), 112.7
(C), 115.4 (CH2), 138.2 (CH), 153.7 (C), 169.2 (C), 170.7 (C). Anal.
Calcd for C16H21NO8: C, 54.08; H, 5.96; N, 3.94. Found: C, 54.11;
H, 5.90; N, 4.00.
C12H17NO5S: C, 50.16; H, 5.96; N, 4.87. Found: C, 50.23; H, 5.93;
N, 4.82.
4.9. A mixture of (4S)-4-[(3aR,6S,6aR)-6-hydroxy-2,2-dimethyl-
tetrahydrofuro[2.3-d][1.3]dioxol-5-yl]-4-vinyloxazolidine-2-one
(4S-12) and (4R)-4-[(3aR,6S,6aR)-6-hydroxy-2,2-dimethyltetra-
hydrofuro[2.3-d][1.3]dioxol-5-yl]-4-vinyloxazolidine-2-one
(4R-12)
Diastereoisomer 14: Rf 0.20 (3:1 hexane–EtOAc); mp 207–
To a solution of the mixture of thiocarbamates 11 (3.37 g,
11.73 mmol) in dry CH3CN (114 mL) was added mesitylnitrile
oxide (2.27 g, 14.1 mmol). The reaction mixture was stirred at
room temperature for 30 min. Evaporation of the solvent left a res-
idue that was purified by column chromatography on silica gel (1:2
211 °C; ½a 2D0
ꢂ
ꢀ51.2 (c 0.26, CHCl3). 1H NMR (CDCl3, 400 MHz): d
1.31 (s, 3H, CH3), 1.51 (s, 3H, CH3), 2.08 (s, 3H, CH3CO), 2.54 (s,
3H, CH3CO), 4.21 (d, J6,6 9.2 Hz, 1H, H-6), 4.47 (d, J2,1 3.7 Hz, 1H,
H-2), 4.75 (d, J6,6 9.2 Hz, 1H, H-6), 5.23 (d, J4,3 3.4 Hz, 1H, H-3),
5.34 (d, J8trans,7 17.5 Hz, 1H, H-8trans), 5.39 (d, J8cis,7 10.9 Hz, 1H,

M. Martinková et al. / Carbohydrate Research 345 (2010) 2427–2437
2433
H-8cis), 5.56 (d, J4,3 3.4 Hz, 1H, H-4), 5.95 (d, J2,1 3.7 Hz, 1H, H-1),
6.14 (dd, J8trans,7 17.5 Hz, J8cis,7 10.9 Hz, 1H, H-7). 13C NMR (CDCl3,
100 MHz): d 21.0 (CH3), 25.6 (CH3), 26.5 (CH3), 26.9 (CH3), 66.3
(C), 67.5 (CH2), 76.1 (CH), 76.7 (CH), 83.5 (CH), 104.7 (CH), 113.0
(C), 117.9 (CH2), 133.6 (CH), 153.5 (C), 168.7 (C), 171.3 (C). Anal.
Calcd for C16H21NO8: C, 54.08; H, 5.96; N, 3.94. Found: C, 54.03;
H, 6.01; N, 3.90.
11.5 Hz, 1H, OCH2Ph), 4.79 (d, JH,H 15.4 Hz, 1H, NCH2Ph), 6.00 (d,
J2,1 3.8 Hz, 1H, H-1), 7.22–7.30 (m, 4H, Ph), 7.35–7.41 (m, 6H,
Ph), 9.60 (s, 1H, CHO). Anal. Calcd for C25H27NO7: C, 66.21; H,
6.00; N, 3.09. Found: C, 66.16; H, 6.06; N, 3.12.
4.13. (4S)-3-Benzyl-4-[(3aR,6S,6aR)-6-(benzyloxy)-2,2-dimeth-
yltetrahydrofuro[2.3-d][1.3]dioxol-5-yl]-4-(hydroxymethyl)-
oxazolidin-2-one (17)
4.11. (4S)-3-Benzyl-4-[(3aR,6S,6aR)-6-(benzyloxy)-2,2-dimethyl-
tetrahydrofuro[2.3-d][1.3]dioxol-5-yl]-4-vinyloxazolidin-2-one
(15)
To a solution of 16 (1.67 g, 3.68 mmol) in MeOH (30 mL) that
was pre-cooled to 0 °C was added NaBH4 (0.154 g, 4.07 mmol).
The resulting mixture was stirred for 10 min at 0 °C and for an
additional 20 min at room temperature. The mixture was neutral-
ized with Amberlite IR-120 (H+). The insoluble materials were re-
moved by filtration, the solvent was evaporated and the residue
was chromatographed on silica gel (1:1 hexane–EtOAc) to afford
To a solution of acetate 13 (1.62 g, 4.56 mmol) in MeOH (51 mL)
was added K2CO3 (0.126 g, 0.91 mmol) at room temperature. After
25 min, at which point no starting material was detected (TLC), the
reaction mixture was then neutralised with Amberlite IR-120 (H+)
and filtered. Evaporation of the solvent and chromatography on
silica gel (1:2 hexane–EtOAc) afforded 1.17 g (95%) of 12S.
Compound 12S (1.17 g, 4.31 mmol) was dissolved in dry DMF
(17.4 mL) and to this solution pre-cooled to 0 °C was added NaH
(0.45 g, 8.53 mmol, 60% dispersion in mineral oil, freed of oil with
anhyd THF). The reaction was stirred for 10 min at 0 °C, then benzyl
bromide (1.51 mL, 12.62 mmol) and tetrabutylammonium iodide
(33 mg, 0.09 mmol) were added at the same temperature. The mix-
ture was allowed to warm to room temperature and the stirring was
continual for another 30 min. The excess hydride was decomposed
with MeOH (1.3 mL) and the mixture was partitioned between ice
water (45 mL) and Et2O (50 mL). The aqueous phase was extracted
with an additional portion of Et2O (50 mL), the combined organic
layers were dried over Na2SO4, the solvent was evaporated and the
residue was chromatographed on silica gel (3:1 hexane–EtOAc) to
1.59 g (95%) of alcohol 17 as a colourless oil: ½a D20
ꢀ65.9 (c 0.19,
ꢂ
CHCl3). 1H NMR (CDCl3, 400 MHz): d 1.28 (s, 3H, CH3), 1.38 (s,
3H, CH3), 3.58 (d, J4,3 3.5 Hz, 1H, H-3), 3.69 (d, JH,H 12.2 Hz, 1H,
CH2O), 3.74 (d, JH,H 12.2 Hz, 1H, CH2O), 4.11 (d, J6,6 8.8 Hz, 1H, H-
6), 4.21 (d, J4,3 3.5 Hz, 1H, H-4), 4.28 (d, J6,6 8.8 Hz, 1H, H-6), 4.41
(d, JH,H 11.4 Hz, 1H, OCH2Ph), 4.46 (d, J2,1 3.9 Hz, 1H, H-2), 4.47
(d, JH,H 15.1 Hz, 1H, NCH2Ph), 4.50 (d, JH,H 11.4 Hz, 1H, OCH2Ph),
4.55 (d, JH,H 15.1 Hz, 1H, NCH2Ph), 5.89 (d, J2,1 3.9 Hz, 1H, H-1),
7.30–7.40 (m, 8H, Ph), 7.42–7.46 (m, 2H, Ph). 13C NMR (CDCl3,
100 MHz): d 26.1 (CH3), 26.6 (CH3), 45.3 (CH2), 63.5 (CH2), 64.9
(C), 66.5 (CH2), 72.1 (CH2), 81.0 (CH), 81.1 (CH), 82.1 (CH), 105.0
(CH), 111.8 (C), 128.0 (CHPh), 128.4 (CHPh), 128.5 (2 ꢃ CHPh),
128.5 (2 ꢃ CHPh), 128.6 (2 ꢃ CHPh), 128.9 (2 ꢃ CHPh), 136.1 (Ci),
138.3 (Ci), 158.9 (C). Anal. Calcd for C25H29NO7: C, 65.92; H, 6.42;
N, 3.08. Found: C, 65.86; H, 6.48; N, 3.12.
give 1.87 g (96%) of compound 15 as a colourless oil: ½a D20
ꢀ58.3
ꢂ
(c 0.23, CHCl3). 1H NMR (CDCl3, 400 MHz): d 1.22 (s, 3H, CH3), 1.24
(s, 3H, CH3), 3.47 (d, J4,3 3.6 Hz, 1H, H-3), 3.97 (d, J6,6 8.7 Hz, 1H,
H-6), 4.10 (d, JH,H 15.1 Hz, 1H, NCH2Ph), 4.17 (d, J4,3 3.6 Hz, 1H,
H-4), 4.28 (d, J6,6 8.7 Hz, 1H, H-6), 4.36 (d, JH,H 11.4 Hz, 1H, OCH2Ph),
4.43 (d, J2,1 3.9 Hz, 1H, H-2), 4.47 (d, JH,H 11.4 Hz, 1H, OCH2Ph), 4.76
(d, JH,H 15.1 Hz, 1H, NCH2Ph), 5.25 (d, J8trans,7 17.6 Hz, 1H, H-8trans),
5.37 (d, J8cis,7 10.8 Hz, 1H, H-8cis), 5.91 (d, J2,1 3.9 Hz, 1H, H-1), 6.09
(dd, J8trans,7 17.6 Hz, J8cis,7 10.8 Hz, 1H, H-7), 7.25–7.45 (m, 10H, Ph).
13C NMR (CDCl3, 100 MHz): d 26.1 (CH3), 26.6 (CH3), 45.8 (CH2),
65.7 (C), 69.7 (CH2), 72.1 (CH2), 81.0 (CH), 81.2 (CH), 82.6 (CH),
105.2 (CH), 111.6 (C), 116.7 (CH2), 127.7 (CHPh), 128.2 (2 ꢃ CHPh),
128.3 (CHPh), 128.5 (2 ꢃ CHPh), 128.6 (2 ꢃ CHPh), 128.8 (2 ꢃ CHPh),
136.3 (CH), 137.6 (Ci), 138.2 (Ci), 158.7 (C). Anal. Calcd for
4.14. (4S)-4-(Acetoxymethyl)-3-benzyl-4-[(3aR,6S,6aR)-6-(ben-
zyloxy)-2,2-dimethyltetrahydrofuro[2.3-d][1.3]dioxol-5-yl]-
oxazolidin-2-one (18)
To a solution of 17 (1.59 g, 3.49 mmol) in pyridine (26.4 mL)
were added DMAP (43 mg, 0.35 mmol) and Ac2O (0.50 mL,
5.29 mmol) at room temperature. After 30 min, no starting com-
pound was detected (TLC) in the reaction mixture, which was then
poured into ice water (50 mL) and extracted with Et2O (3 ꢃ 35 mL).
The combined organic layers were dried over Na2SO4, the solvent
was evaporated in vacuo, and the residue was subjected to flash
chromatography on silica gel (3:1 hexane–EtOAc) to afford 1.63 g
(94%) of crystalline derivative 18: mp 158–160 °C; ½a D20
ꢀ80.8 (c
ꢂ
0.23, CHCl3). 1H NMR (CDCl3, 400 MHz): d 1.27 (s, 3H, CH3), 1.28
(s, 3H, CH3), 1.98 (s, 3H, CH3CO), 3.69 (d, J4,3 3.6 Hz, 1H, H-3),
4.11 (s, 2H, 2 ꢃ H-6), 4.19 (d, J4,3 3.6 Hz, 1H, H-4), 4.27 (d, JH,H
12.4 Hz, 1H, CH2O), 4.36 (d, JH,H 15.3 Hz, 1H, NCH2Ph), 4.39 (d,
JH,H 11.6 Hz, 1H, OCH2Ph), 4.44 (d, JH,H 12.4 Hz, 1H, CH2O), 4.47
(d, J2,1 3.8 Hz, 1H, H-2), 4.53 (d, JH,H 15.3 Hz, 1H, NCH2Ph), 4.55
(d, JH,H 11.6 Hz, 1H, OCH2Ph), 5.91 (d, J2,1 3.8 Hz, 1H, H-1), 7.24–
7.44 (m, 10H, Ph). 13C NMR (CDCl3, 100 MHz): d 20.6 (CH3), 26.1
(CH3), 26.6 (CH3), 45.1 (CH2), 63.8 (CH2), 63.8 (C), 66.8 (CH2),
72.0 (CH2), 80.8 (CH), 81.9 (CH), 82.0 (CH), 105.1 (CH), 111.9 (C),
127.7 (CHPh), 128.4 (2 ꢃ CHPh), 128.5 (2 ꢃ CHPh), 128.5 (CHPh),
128.6 (2 ꢃ CHPh), 128.7 (2 ꢃ CHPh), 135.9 (Ci), 137.8 (Ci), 158.4
(C), 170.4 (C). Anal. Calcd for C27H31NO8: C, 65.18; H, 6.28; N,
2.82. Found: C, 65.25; H, 6.23; N, 2.92.
C26H29NO6: C, 69.16; H, 6.47; N, 3.10. Found: C, 69.21; H, 6.42; N,
3.12.
4.12. (4S)-3-Benzyl-4-[(3aR,6S,6aR)-6-(benzyloxy)-2,2-dimethyl-
tetrahydrofuro[2.3-d][1.3]dioxol-5-yl]-2-oxooxazolidine-4-
carbaldehyde (16)
Ozone was introduced into a solution of 15 (1.87 g, 4.14 mmol)
in dry MeOH (118 mL) at ꢀ78 °C for 1 h. This resulted in the forma-
tion of a slightly blue solution. Dry N2 was passed through the cold
solution in order to remove excess of ozone. Then, Ph3P (1.09 g,
4.14 mmol) in CH2Cl2 (60 mL) was added and the stirred mixture
was allowed to warm to room temperature. After 1.5 h, the solvent
was evaporated, and the residue was purified by column chroma-
tography on silica gel (1:1 hexane–EtOAc) to afford 1.67 g (89%) of
aldehyde 16 as a colourless oil that was used immediately in the
next step. 1H NMR (CDCl3, 400 MHz): d 1.25 (s, 3H, CH3), 1.30 (s,
3H, CH3), 3.77 (d, J6,6 9.6 Hz, 1H, H-6), 3.94 (d, J4,3 3.6 Hz, 1H, H-3
or H-4), 4.30 (d, J6,6 9.6 Hz, 1H, H-6), 4.37 (d, JH,H 15.4 Hz, 1H,
NCH2Ph), 4.39 (d, JH,H 11.5 Hz, 1H, OCH2Ph), 4.46 (d, J4,3 3.6 Hz,
1H, H-3 or H-4), 4.61 (d, J2,1 3.8 Hz, 1H, H-2), 4.63 (d, JH,H
4.15. Ethyl (4S,5R,6R,2E)-6-[(S)-40-(acetoxymethyl)-30-benzyl-20-
oxooxazolidin-40-yl]-5-(benzyloxy)-4,6-dihydroxyhex-2-enoate
(20)
Compound 18 (1.63 g, 3.28 mmol) was treated with a mixture
of 4:1 TFA–H2O (27 mL) for 1.5 h at room temperature. The solvent

2434
M. Martinková et al. / Carbohydrate Research 345 (2010) 2427–2437
was removed under reduced pressure, and the residue was sub-
jected to flash chromatography through a short column of silica
gel (1:2 hexane–EtOAc) to afford 1.41 g (94%) of furanose 19 as a
colourless oil. The obtained lactol 19 (1.41 g, 3.08 mmol) was dis-
solved in dry dichloromethane (18 mL), and to this solution were
successively added benzoic acid (38 mg, 0.31 mmol) and the stabi-
lized ylide, Ph3P@CHCO2Et, (3.20 g, 9.19 mmol) at room tempera-
ture. After 19 h, the mixture did not contain (TLC) any starting
compound 19. Evaporation of the solvent and chromatography of
the residue on silica gel (1:1 hexane/EtOAc) gave 1.48 g (91%) of
unsaturated ester 20 as a colourless oil which was used immedi-
ately in the next step to avoid problems connected with its possible
instability. 1H NMR (CDCl3, 400 MHz): d 1.31 (t, J 7.1 Hz, 3H, CH3),
1.97 (s, 3H, CH3CO), 3.45 (m, 1H, H-5), 3.84 (m, 1H, H-6), 3.93 (m,
insoluble materials were removed by filtration, the solvent was
evaporated and the residue was chromatographed on silica gel
(1:1 hexane–EtOAc). This procedure yielded 1.05 g (92%) of 22 as
a colourless oil: ½a D20
ꢂ
ꢀ45.3 (c 0.40, CHCl3). 1H NMR (CDCl3,
400 MHz): d 1.25 (t, J 7.1 Hz, 3H, CH3), 1.29 (s, 3H, CH3), 1.39 (s,
3H, CH3), 2.84 (m, 1H, H-5), 3.70 (d, JH,H 11.9 Hz, 1H, CH2O), 3.74
(d, JH,H 11.9 Hz, 1H, CH2O), 3.84 (d, J5 ,5 8.6 Hz, 1H, H-50), 3.96 (d,
J6,5 1.4 Hz, 1H, H-6), 4.04 (ddd, J4,3 4.7 Hz, J4,2 1.8 Hz, J5,4 1.4 Hz,
1H, H-4), 4.17 (q, J 7.1 Hz, 2H, CH2), 4.24 (d, JH,H 10.2 Hz, 1H,
OCH2Ph), 4.39 (d, JH,H 10.2 Hz, 1H, OCH2Ph), 4.55 (d, JH,H 15.2 Hz,
0
0
50,50
1H, NCH2Ph), 4.64 (d, JH,H 15.2 Hz, 1H, NCH2Ph), 4.91 (d, J
8.6 Hz, 1H, H-50), 6.04 (dd, J3,2 15.6 Hz, J4,2 1.8 Hz, 1H, H-2), 6.78
(dd, J3,2 15.6 Hz, J4,3 4.7 Hz, 1H, H-3), 7.29–7.31 (m, 5H, Ph),
7.39–7.42 (m, 3H, Ph), 7.50–7.52 (m, 2H, Ph). 13C NMR (CDCl3,
100 MHz): d 14.2 (CH3), 18.8 (CH3), 29.2 (CH3), 45.7 (CH2), 60.5
(CH2), 64.1 (CH2), 65.6 (C), 66.1 (CH2), 71.6 (CH), 72.0 (CH), 72.8
(CH), 74.3 (CH2), 99.4 (C), 122.3 (CH), 127.7 (CHPh), 128.1
(2 ꢃ CHPh), 128.3 (2 ꢃ CHPh), 128.4 (CHPh), 128.9 (2 ꢃ CHPh),
129.0 (2 ꢃ CHPh), 137.1 (Ci), 138.5 (Ci), 143.2 (CH), 159.3 (C),
166.0 (C). Anal. Calcd for C29H35NO8: C, 66.27; H, 6.71; N, 2.66.
Found: C, 66.35; H, 6.65; N, 2.73.
1H, H-4), 3.97 (d, J5 ,5 9.1 Hz, 1H, H-50), 4.20 (d, JH,H 12.5 Hz, 1H,
CH2O), 4.21 (q, J = 7.1 Hz, 2H, CH2), 4.29 (d, JH,H 12.5 Hz, 1H,
CH2O), 4.36 (d, JH,H 15.6 Hz, 1H, NCH2Ph), 4.55–4.59 (m, 3H,
0
0
NCH2Ph, OCH2Ph), 4.96 (d, J5 ,5 9.1 Hz, 1H, H-50), 6.01 (dd, J3,2
15.7 Hz, J4,2 2.0 Hz, 1H, H-2), 6.78 (dd, J3,2 15.7 Hz, J4,3 4.2 Hz, 1H,
H-3), 7.28–7.43 (m, 10H, Ph). 13C NMR (CDCl3, 100 MHz): d 14.2
(CH3), 20.6 (CH3), 45.3 (CH2), 60.6 (CH2), 63.6 (CH2), 65.3 (C),
65.4 (CH2), 70.0 (CH), 71.6 (CH), 74.2 (CH2), 76.5 (CH), 121.6
(CH), 128.1 (CHPh), 128.5 (4 ꢃ CHPh), 128.6 (CHPh), 128.7
(2 ꢃ CHPh), 128.8 (2 ꢃ CHPh), 136.4 (Ci), 137.5 (Ci), 145.9 (CH),
159.0 (C), 166.0 (C), 170.2 (C). Anal. Calcd for C28H33NO9: C,
63.75; H, 6.30; N, 2.65. Found: C, 63.71; H, 6.33; N, 2.69.
0
0
4.18. Ethyl (4S,5R,6R,2E)-6-[(R)-30-benzyl-40-[(tert-butyldimeth-
ylsilyloxy)methyl]-20-oxooxazolidin-40-yl]-5-(benzyloxy)-4,6-
(isopropylidenedioxy)hex-2-enoate (23)
To
a solution of 22 (1.05 g, 2.00 mmol) and 2,6-lutidine
4.16. Ethyl (4S,5R,6R,2E)-6-[(S)-40-(acetoxymethyl)-30-benzyl-20-
oxooxazolidin-40-yl]-5-(benzyloxy)-4,6-(isopropylidenedioxy)-
hex-2-enoate (21)
(0.70 mL, 6.01 mmol) in dry CH2Cl2 (12.3 mL), pre-cooled to 0 °C,
was added tert-butyldimethylsilyl trifluoromethanesulfonate
(0.69 mL, 3.00 mmol). The reaction mixture was stirred at room
temperature for 30 min and then poured into satd aq NaHCO3
(30 mL). The aq phase was extracted with additional portions of
CH2Cl2 (2 ꢃ 25 mL). The combined organic layers were dried over
Na2SO4, the solvent was evaporated, and the residue was purified
by flash chromatography on silica gel (5:1 hexane–EtOAc) to give
To a solution of ester 20 (1.41 g, 2.67 mmol) in 2,2-dimethoxy-
propane (22.8 mL) was added CSA (0.123 g, 0.53 mmol) at room
temperature. After being stirred for 3 h, the solvent was evapo-
rated in vacuo and the residue was partitioned between CH2Cl2
(50 mL) and satd aq NaHCO3 (15 mL). The organic layer was dried
over Na2SO4, and concentrated, and the residue was purified by
flash chromatography on silica gel (2:1 hexane–EtOAc) to afford
1.20 g (94%) of crystalline compound 23; mp 147–149 °C; ½a D20
ꢂ
+46.3 (c 0.30, CHCl3); IR (KBr) mmax (cmꢀ1) 2956, 2931, 1724,
1656, 1472, 1414, 1261, 1185. 1H NMR (CDCl3, 400 MHz): d 0.09
(s, 3H, CH3), 0.12 (s, 3H, CH3), 0.93 (s, 9H, 3 ꢃ CH3), 1.23 (s, 3H,
CH3), 1.25 (t, J 7.1 Hz, 3H, CH3), 1.35 (s, 3H, CH3), 2.50 (dd, J5,4
1.23 g (81%) of 21 as a colourless oil: ½a D20
ꢀ44.2 (c 0.27, CHCl3).
ꢂ
1H NMR (CDCl3, 400 MHz): d 1.20 (s, 3H, CH3), 1.26 (t, J 7.1 Hz,
3H, CH3), 1.37 (s, 3H, CH3), 2.05 (s, 3H, CH3CO), 2.77 (t,
J6,5 = 1.4 Hz, J5,4 1.4 Hz, 1H, H-5), 3.80 (d, J6,5 1.4 Hz, 1H, H-6),
1.4 Hz, J6,5 1.3 Hz, 1H, H-5), 3.69 (d, J5 ,5 8.4 Hz, 1H, H-50), 3.70 (d,
JH,H 10.8 Hz, 1H, CH2O), 3.81–3.86 (m, 3H, H-4, H-6, CH2O), 4.07
(d, JH,H 10.1 Hz, 1H, OCH2Ph), 4.17 (q, J 7.1 Hz, 2H, CH2), 4.22 (d,
JH,H 15.0 Hz, 1H, NCH2Ph), 4.29 (d, JH,H 10.1 Hz, 1H, OCH2Ph), 4.98
0
0
3.84 (d, J5 ,5 8.8 Hz, 1H, H-50), 3.96 (ddd, J4,3 4.7 Hz, J4,2 1.8 Hz, J5,4
1.4 Hz, 1H, H-4), 4.17 (q, J = 7.1 Hz, 2H, CH2), 4.18 (d, JH,H 12.4 Hz,
1H, CH2O), 4.20 (d, JH,H 10.4 Hz, 1H, OCH2Ph), 4.24 (d, JH,H
15.4 Hz, 1H, NCH2Ph), 4.34 (d, JH,H 10.4 Hz, 1H, OCH2Ph), 4.37 (d,
JH,H 12.4 Hz, 1H, CH2O), 4.78 (d, JH,H 15.4 Hz, 1H, NCH2Ph), 4.96
0
0
(d, J5 ,5 8.4 Hz, 1H, H-50), 4.98 (d, JH,H 15.0 Hz, 1H, NCH2Ph), 5.95
(dd, J3,2 15.6 Hz, J4,2 1.7 Hz, 1H, H-2), 6.63 (dd, J3,2 15.6 Hz, J4,3
4.8 Hz, 1H, H-3), 7.25–7.30 (m, 5H, Ph), 7.37–7.43 (m, 3H, Ph),
7.49–7.53 (m, 2H, Ph). 13C NMR (CDCl3, 100 MHz): d ꢀ5.7 (CH3),
ꢀ5.5 (CH3), 14.1 (CH3), 18.1 (C), 18.8 (CH3), 25.7 (3 ꢃ CH3), 29.1
(CH3), 45.9 (CH2), 60.3 (CH2), 64.6 (CH2), 65.7 (C), 66.4 (CH2),
71.0 (CH), 72.0 (CH), 72.7 (CH), 74.3 (CH2), 99.1 (C), 122.0 (CH),
127.6 (CHPh), 128.1 (2 ꢃ CHPh), 128.1 (CHPh), 128.4 (2 ꢃ CHPh),
128.8 (2 ꢃ CHPh), 129.2 (2 ꢃ CHPh), 137.1 (Ci), 138.8 (Ci), 143.3
(CH), 159.5 (C), 165.9 (C). Anal. Calcd for C35H49NO8Si: C, 65.70;
H, 7.72; N, 2.19. Found: C, 65.63; H, 7.75; N, 2.13.
0
0
(d, J5 ,5 8.8 Hz, 1H, H-50), 6.01 (dd, J3,2 15.6 Hz, J4,2 1.8 Hz, 1H, H-
2), 6.72 (dd, J3,2 15.6 Hz, J4,3 4.7 Hz, 1H, H-3), 7.27–7.33 (m, 5H,
Ph), 7.36–7.43 (m, 3H, Ph), 7.44–7.48 (m, 2H, Ph). 13C NMR (CDCl3,
100 MHz): d 14.2 (CH3), 18.5 (CH3), 20.7 (CH3), 29.1 (CH3), 45.7
(CH2), 60.5 (CH2), 64.0 (CH2), 64.3 (C), 66.1 (CH2), 71.7 (CH), 72.1
(CH), 72.6 (CH), 74.4 (CH2), 99.5 (C), 122.4 (CH), 127.8 (CHPh),
128.2 (2 ꢃ CHPh), 128.3 (CHPh), 128.4 (2 ꢃ CHPh), 128.8 (2 ꢃ CHPh),
128.9 (2 ꢃ CHPh), 136.9 (Ci), 138.1 (Ci), 142.9 (CH), 159.0 (C), 165.9
(C), 170.3 (C). Anal. Calcd for C31H37NO9: C, 65.59; H, 6.57; N, 2.47.
Found: C, 65.55; H, 6.63; N, 2.53.
0
0
4.19. (4R)-3-Benzyl-4-[(10R,20R,30S,40E)-20-(benzyloxy)-60-
hydroxy-10,30-(isopropylidenedioxy)hex-40-enyl]-4-[(tert-
butyldimethylsilyloxy)methyl]oxazolidin-2-one (25)
4.17. Ethyl (4S,5R,6R,2E)-6-[(S)-30-benzyl-40-(hydroxymethyl)-20-
oxooxazolidin-40-yl]-5-(benzyloxy)-4,6-(isopropylidenedioxy)-
hex-2-enoate (22)
Diisobutylaluminum hydride (2.5 mL of a 1.2 M toluene solu-
tion) was added dropwise to a solution of ester 23 (1.07 g,
1.67 mmol) in dry CH2Cl2 (21 mL) that was pre-cooled to ꢀ78 °C.
The resulting mixture was stirred at the same temperature for
30 min and then quenched with MeOH (1.0 mL). The mixture
was warmed to room temperature and poured into 30% aq K/Na
NaOEt (29.4 mg, 0.43 mmol) was added to a solution of 21
(1.23 g, 2.17 mmol) in EtOH (13.7 mL) that was pre-cooled to
0 °C. The reaction mixture was stirred at 0 °C for 1 h, then neutral-
ized with Amberlite IR-120 (H+) at the same temperature. The

M. Martinková et al. / Carbohydrate Research 345 (2010) 2427–2437
2435
tartrate (12.3 mL). After being stirred for 30 min, the mixture was
then extracted with CH2Cl2 (3 ꢃ 20 mL). The combined organic lay-
ers were dried over Na2SO4, the solvent was evaporated in vacuo,
and the crude product was chromatographed on silica gel (1:1 hex-
(m, 8H, Ph), 7.49–7.54 (m, 2H, Ph). 13C NMR (CDCl3, 100 MHz): d
ꢀ5.7 (CH3), ꢀ5.5 (CH3), 18.1 (C), 18.9 (CH3), 25.8 (3 ꢃ CH3), 29.3
(CH3), 31.7 (CH2), 45.9 (CH2), 64.6 (CH2), 65.8 (C), 66.4 (CH2),
70.9 (CH), 72.9 (CH), 73.7 (CH), 74.5 (CH2), 99.1 (C), 127.6 (CHPh),
128.0 (CHPh), 128.1 (2 ꢃ CHPh), 128.2 (2 ꢃ CHPh), 128.3 (CH),
128.8 (2 ꢃ CHPh), 129.2 (2 ꢃ CHPh), 132.1 (CH), 137.7 (Ci), 138.9
(Ci), 159.5 (C). Anal. Calcd for C33H46BrNO6Si: C, 59.99; H, 7.02;
N, 2.12. Found: C, 60.03; H, 6.98; N, 2.15.
ane–EtOAc) to afford 0.35 g (35%) of a,b-unsaturated aldehyde 24
(compound 24 was subsequently converted into corresponding
alcohol 25 using the same procedure as described for the prepara-
tion of compound 17) and 0.51 g (51%) of crystalline allylic alcohol
25: mp 205–207 °C; ½a D20
ꢂ
+58.8 (c 0.21, CHCl3). 1H NMR (CDCl3,
400 MHz): d 0.08 (s, 3H, CH3), 0.11 (s, 3H, CH3), 0.93 (s, 9H,
4.21. (4R)-3-Benzyl-4-[(10R,20R,30S,70S&R,40E)-20-(benzyloxy)-
120,120-ethylenedioxy-10,30-(isopropylidenedioxy)-70-(phenyl-
sulfonyl)octadec-40-enyl]-4-[(tert-butyldimethylsilyloxy)-
methyl]oxazolidin-2-one (27)
0
0
3 ꢃ CH3), 1.23 (s, 3H, CH3), 1.36 (s, 3H, CH3), 2.50 (t, J2 ,1 1.4 Hz,
J3 ,2 1.4 Hz, 1H, H-20), 3.69–3.75 (m, 3H, H-30, H-5, CH2O), 3.83 (d,
0
0
J2 ,1 1.4 Hz, 1H, H-10), 3.84 (d, JH,H 10.6 Hz, 1H, CH2O), 4.00 (m,
2H, 2 ꢃ H-60), 4.18 (d, JH,H 10.8 Hz, 1H, OCH2Ph), 4.23 (d, JH,H
15.1 Hz, 1H, NCH2Ph), 4.44 (d, JH,H 10.8 Hz, 1H, OCH2Ph), 4.95 (d,
JH,H 15.1 Hz, 1H, NCH2Ph), 4.99 (d, J5,5 8.4 Hz, 1H, H-5), 5.49 (tdd,
0
0
n-BuLi (0.94 mL, 1.6 M solution in hexane) was added dropwise
to a solution of sulfone 26a (0.368 g, 0.999 mmol) in dry THF
(8.1 mL) that was pre-cooled to ꢀ78 °C. The resulting yellow solu-
tion was stirred for 30 min at the same temperature. Then, the
solution of bromide 26 (0.22 g, 0.333 mmol) in dry THF (9.8 mL)
was added dropwise at ꢀ78 °C. The reaction mixture was stirred
for 10 min at ꢀ78 °C, then poured into satd aq NH4Cl (16 mL)
and extracted with EtOAc (2 ꢃ 20 mL). The combined organic lay-
ers were dried over Na2SO4, the solvent was evaporated, and the
residue was chromatographed on silica gel (5:1 hexane–EtOAc)
to give 0.30 g (95%) of a mixture of diastereoisomeric coupling
products 27 as a colourless oil: IR (KBr) mmax (cmꢀ1) 2951, 2859,
1746, 1471, 1447, 1408, 1304, 1260, 1203, 1146, 1070, 978, 839,
731. 1H NMR (CDCl3, 400 MHz): d 0.07 (s, 2.1H, CH3min.), 0.07 (s,
3H, CH3maj.), 0.10 (s, 2.1H, CH3min.), 0.10 (s, 3H, CH3maj.), 0.86–
0.90 (m, 5.1H, CH3maj., CH3min.), 0.92 (s, 6.3H, 3 ꢃ CH3min.),
0.92 (s, 9H, 3 ꢃ CH3maj.), 1.20–1.82 (m, 40.8H, 2 ꢃ CH3maj.,
2 ꢃ CH3min., 9 ꢃ CH2maj., 9 ꢃ CH2min.), 2.25–2.33 (m, 1.7H, H-
60maj., H-60min.), 2.39–2.44 (m, 1.7H, H-60maj., H-60min.), 2.45
(m, 1H, H-20maj.), 2.48 (m, 0.7H, H-20min.), 2.83–2.93 (m, 1.7H,
H-70min., H-70maj.), 3.64–3.75 (m, 5.1H, H-30maj., H-30min., CH2O-
maj., CH2Omin., H-5maj., H-5 min.), 3.81–3.93 (m, 10.2H,
2 ꢃ CH2maj., 2 ꢃ CH2min., CH2Omaj., CH2Omin., H-10maj., H-
10min.), 4.18 (m, 1.7H, OCH2Phmaj., OCH2Phmin.), 4.22 (d, 1H,
JH,H 15.2 Hz, NCH2Phmaj.), 4.22 (d, 0.7H, JH,H 15.1 Hz, NCH2Phmin.),
4.37 (d, 1H, JH,H 10.7 Hz, OCH2Phmaj.), 4.38 (d, 0.7H, JH,H 10.8 Hz,
OCH2Phmin.), 4.91–4.97 (m, 3.4H, H-5maj., H-5 min., NCH2Phmaj.,
NCH2Phmin.), 5.35–5.43 (m, 1.7H, H-40maj., H-40min.), 5.51–5.59
(m, 0.7H, H-50min.), 5.60–5.66 (m, 1H, H-50maj.), 7.25–7.30 (m,
8.5H, Phmaj., Phmin.), 7.37–7.42 (m, 5.1H, Phmaj., Phmin.), 7.48–
7.51 (m, 3H, Phmaj., Phmin.), 7.52–7.57 (m, 3H, Phmaj.), 7.62–
7.67 (m, 2.1 H, Phmin.), 7.80–7.83 (m, 1.4H, Phmin.), 7.84–7.87
(m, 2H, Phmaj.). Anal. Calcd for C53H77NO10SSi: C, 67.13; H, 8.18;
N, 1.48. Found: C, 67.10; H, 8.13; N, 1.45.
J5 ,4 15.6 Hz, J4 ,3 6.2 Hz, J6 ,4 1.4 Hz, J6 ,4 1.4 Hz, 1H, H-40), 5.70
0
0
0
0
0
0
0
0
(dtd, J5 ,4 15.6 Hz, J6 ,5 5.2 Hz, J6 ,5 5.2 Hz, J5 ,3 0.9 Hz, 1H, H-50),
7.27–7.41 (m, 8H, Ph), 7.48–7.52 (m, 2H, Ph). 13C NMR (CDCl3,
100 MHz): d ꢀ5.7 (CH3), ꢀ5.5 (CH3), 18.2 (C), 18.9 (CH3), 25.8
(3 ꢃ CH3), 29.4 (CH3), 45.9 (CH2), 62.8 (CH2), 64.6 (CH2), 65.8 (C),
65.5 (CH2), 71.1 (CH), 73.0 (CH), 73.8 (CH), 74.5 (CH2), 99.0 (C),
127.6 (CHPh), 127.9 (CH), 128.0 (2 ꢃ CHPh), 128.1 (CHPh), 128.2
(2 ꢃ CHPh), 128.7 (2 ꢃ CHPh), 129.2 (2 ꢃ CHPh), 131.4 (CH), 137.9
(Ci), 138.8 (Ci), 159.6 (C). Anal. Calcd for C33H47NO7Si: C, 66.30;
H, 7.92; N, 2.34. Found: C, 66.36; H, 7.95; N, 2.30.
0
0
0
0
0
0
0
0
Aldehyde 24: a colourless syrup; 1H NMR (CDCl3, 400 MHz): d
0.11 (s, 3H, CH3), 0.14 (s, 3H, CH3), 0.95 (s, 9H, 3 ꢃ CH3), 1.27 (s,
3H, CH3), 1.38 (s, 3H, CH3), 2.55 (m, 1H, H-5), 3.70–3.73 (m, 2H,
H-50, CH2O), 3.84–3.88 (m, 3H, H-4, H-6, CH2O), 4.01 (d, JH,H
10.8 Hz, 1H, OCH2Ph), 4.24 (d, JH,H 15.1 Hz, 1H, NCH2Ph), 4.42 (d,
JH,H 10.8 Hz, 1H, OCH2Ph), 4.99–5.02 (m, 2H, H-50, NCH2Ph), 6.09
(ddd, J3,2 15.7 Hz, J2,CHO 7.7 Hz, J4,2 1.3 Hz, 1H, H-2), 6.29 (dd, J3,2
15.7 Hz, J4,3 4.9 Hz, 1H, H-3), 7.19–7.30 (m, 5H, Ph), 7.39–7.44
(m, 3H, Ph), 7.54–7.56 (m, 2H, Ph), 9.31 (d, J2,CHO 7.7 Hz, 1H,
CHO). Anal. Calcd for C33H45NO7Si: C, 66.52; H, 7.61; N, 2.35.
Found: C, 66.48; H, 7.65; N, 2.32.
4.20. (4R)-3-Benzyl-4-[(10R,20R,30S,40E)-20-(benzyloxy)-60-bromo-
10,30-(isopropylidenedioxy)hex-40-enyl]-4-[(tert-butyldimethyl-
silyloxy)methyl]oxazolidin-2-one (26)
To a solution of allylic alcohol 25 (0.33 g, 0.55 mmol) in dry
CH2Cl2 (8.7 mL) was added Et3N (0.193 mL, 1.38 mmol), followed
by dropwise addition of methanesulfonyl chloride (0.106 mL,
1.38 mmol) at 0 °C. After stirring at room temperature for
30 min, the solvent was evaporated in vacuo and the residue was
diluted with Et2O (5 mL). The insoluble materials were removed
by filtration, the solvent was evaporated and the crude product
was used directly in the next step without further purification.
To a solution of crude mesylate (0.37 g, 0.547 mmol) in dry THF
(8.7 mL) was added LiBr (0.475 g, 5.47 mmol). After stirring at
room temperature for 40 min, the solvent was evaporated under
reduced pressure. The residue was diluted with Et2O (7 mL), the
salts were removed by filtration, and washed with Et2O, and the
solvent was removed in vacuo. The residue was subjected to flash
chromatography through a short column of silica gel (7:1 hexane–
EtOAc) to afford 0.312 g (85.5%) of crystalline bromide 26: mp
4.22. (4R)-3-Benzyl-4-[(10R,20R,30S,40E)-20-(benzyloxy)-120,120-
ethylenedioxy-10,30-(isopropylidenedioxy)octadec-40-enyl]-4-
[(tert-butyldimethylsilyloxy)methyl]oxazolidin-2-one (28)
Na2HPO4 (0.66 g, 4.6 mmol) and sodium amalgam (1.6 g,
4.2 mmol, 6%) were added to a solution of 27 (0.20 g, 0.21 mmol)
in dry MeOH (4.1 mL) that was pre-cooled to 0 °C. The reaction
mixture was stirred for 1 h at room temperature and then another
portion of Na2HPO4 (0.66 g, 4.6 mmol) and sodium amalgam (1.6 g,
4.2 mmol, 6%) was added at 0 °C. This procedure was repeated
twice at 1-h intervals, so that the total amount of Na2HPO4 was
2.64 g (18.48 mmol) and the total amount of sodium amalgam
was 6.56 g (16.8 mmol). The mixture was then diluted with CH2Cl2
(25 mL) and filtered through a pad of Celite. The filtrate was
washed with ice water (8 mL), and dried over Na2SO4, and the sol-
vent was evaporated under reduced pressure. The residue was
purified by flash chromatography on silica gel (7:1 hexane–EtOAc)
153–155 °C;
½
a 2D0
ꢂ
+60.9 (c 0.26, CHCl3). 1H NMR (CDCl3,
400 MHz): d 0.09 (s, 3H, CH3), 0.12 (s, 3H, CH3), 0.93 (s, 9H,
0
0
3 ꢃ CH3), 1.23 (s, 3H, CH3), 1.34 (s, 3H, CH3), 2.41 (t, J3 ,2 1.4 Hz,
J2 ,1 1.4 Hz, 1H, H-20), 3.65–3.74 (m, 3H, H-10, H-5, CH2O), 3.74–
3.87 (m, 4H, H-30, 2 ꢃ H-60, CH2O), 4.18 (d, JH,H 10.7 Hz, 1H,
OCH2Ph), 4.21 (d, JH,H 15.3 Hz, 1H, NCH2Ph), 4.39 (d, JH,H 10.7 Hz,
1H, OCH2Ph), 4.98 (d, JH,H 15.1 Hz, 1H, NCH2Ph), 4.99 (d, J5,5
8.4 Hz, 1H, H-5), 5.52 (m, 1H, H-40), 5.72 (m, 1H, H-50), 7.27–7.43
0
0

2436
M. Martinková et al. / Carbohydrate Research 345 (2010) 2427–2437
to give 0.11 g (64%) of product 28 as a colourless oil: ½a D20
ꢂ
+21.3 (c
was poured into ice water (6.5 mL) and extracted with Et2O
(5 ꢃ 10 mL). The combined organic layers were dried over Na2SO4,
the solvent was evaporated in vacuo and the residue was subjected
to flash chromatography through a short column of silica gel (9:1
CH2Cl2–MeOH). This afforded 50 mg (65%) of carboxylic acid 30
0.25, CHCl3). 1H NMR (CDCl3, 600 MHz): d 0.07 (s, 3H, CH3), 0.10 (s,
3H, CH3), 0.88 (t, 3H, J = 6.9 Hz, CH3), 0.92 (s, 9H, 3 ꢃ CH3), 1.21 (s,
3H, CH3), 1.24–1.33 (m, 16H, 8 ꢃ CH2), 1.34 (s, 3H, CH3), 1.56–1.60
(m, 4H, 2 ꢃ CH2), 1.88–2.02 (m, 2H, 2 ꢃ H-60), 2.45 (t, J2 ,1 = 1.4 Hz,
0
0
J3 ,2 = 1.4 Hz, 1H, H-20), 3.65 (m, 1H, H-30), 3.70 (d, JH,H = 10.7 Hz,
as a colourless oil: ½a D20
ꢂ
+20.1 (c 0.20, CH3OH). 1H NMR (CD3OD,
0
0
0
0
1H, CH2O), 3.71 (d, J5,5 = 8.4 Hz, 1H, H-5), 3.81 (d, J2 ,1 = 1.4 Hz,
1H, H-10), 3.83 (d, JH,H = 10.7 Hz, 1H, CH2O), 3.89–3.93 (m, 4H,
2 ꢃ CH2), 4.22 (d, JH,H = 15.1 Hz, 1H, NCH2Ph), 4.27 (d,
JH,H = 10.5 Hz, 1H, OCH2Ph), 4.36 (d, JH,H = 10.5 Hz, 1H, OCH2Ph),
4.94 (d, JH,H = 15.1 Hz, 1H, NCH2Ph), 4.97 (d, J5,5 = 8.4 Hz, 1H, H-
600 MHz): d 0.90 (t, J = 6.8 Hz, 3H, CH3), 1.25–1.38 (m, 19H, CH3,
8 ꢃ CH2), 1.39 (s, 3H, CH3), 1.53–1.58 (m, 4H, 2 ꢃ CH2), 1.92–2.06
(m, 2H, 2 ꢃ H-60), 2.40 (m, 1H, H-20), 3.84–3.91 (m, 5H, 2 ꢃ CH2,
H-30), 4.23 (d, JH,H = 10.2 Hz, 1H, OCH2Ph), 4.30 (m, 2H, OCH2Ph,
NCH2Ph), 4.67 (m, 2H, H-5, H-10), 4.85 (m, 1H, NCH2Ph), 5.06 (d,
0
0
0
0
0
0
0
0
0
0
5), 5.38 (tdd, J5 ,4 = 15.4 Hz, J4 ,3 = 7.3 Hz, J6 ,4 = 1.2 Hz,
J5,5 = 7.6 Hz, 1H, H-5), 5.35 (dd, J5 ,4 = 15.5 Hz, J4 ,3 = 7.0 Hz, 1H,
H-40), 5.54 (m, 1H, H-50), 7.25–7.35 (m, 5H, Ph), 7.35–7.44 (m,
3H, Ph), 7.54–7.59 (m, 2H, Ph). 13C NMR (CD3OD, 150 MHz): d
14.5 (CH3), 19.3 (CH3), 23.7 (CH2), 24.9 (2 ꢃ CH2), 29.6 (CH3),
30.0 (CH2), 30.3 (CH2), 30.7 (CH2), 30.8 (CH2), 33.0 (CH2), 33.3
(CH2), 38.1 (CH2), 38.1 (CH2), 47.9 (CH2), 65.9 (2 ꢃ CH2), 68.9
(CH2), 70.6 (C), 72.5 (CH), 75.3 (CH), 75.9 (CH2), 76.2 (CH), 100.7
(C), 113.0 (C), 128.7 (CH), 128.8 (CHPh), 129.3 (2 ꢃ CHPh), 129.4
(2 ꢃ CHPh), 129.5 (CHPh), 129.9 (2 ꢃ CHPh), 130.8 (2 ꢃ CHPh),
134.6 (CH), 139.2 (Ci), 139.7 (Ci), 161.5 (C), 174.2 (C). Anal. Calcd
for C41H57NO9: C, 69.56; H, 8.12; N, 1.98. Found: C, 69.60; H,
8.13; N, 1.95.
J6 ,4 = 1.2 Hz, 1H, H-40), 5.50 (td, J5 ,4 = 15.4 Hz, J6 ,5 = 6.6 Hz,
0
0
0
0
0
0
J6 ,5 = 6.6 Hz, 1H, H-50), 7.25–7.27 (m, 1H, Ph), 7.29–7.39 (m, 7H,
Ph), 7.48–7.51 (m, 2H, Ph). 13C NMR (CDCl3, 100 MHz): d ꢀ5.7
(CH3), ꢀ5.5 (CH3), 14.1 (CH3), 18.1 (C), 18.9 (CH3), 22.6 (CH2),
23.8 (CH2), 23.8 (CH2), 25.8 (3 ꢃ CH3), 28.8 (CH2), 29.3 (CH3),
29.4 (CH2), 29.6 (CH2), 29.8 (CH2), 31.8 (CH2), 32.3 (CH2), 37.1
(2 ꢃ CH2), 45.9 (CH2), 64.5 (CH2), 64.9 (2 ꢃ CH2), 65.8 (C), 66.5
(CH2), 71.1 (CH), 73.3 (CH), 74.5 (CH2), 74.9 (CH), 98.9 (C), 111.8
(C), 127.0 (CH), 127.5 (CHPh), 128.0 (CHPh), 128.1 (2 ꢃ CHPh),
128.1 (2 ꢃ CHPh), 128.7 (2 ꢃ CHPh), 129.1 (2 ꢃ CHPh), 133.8 (CH),
137.8 (Ci), 138.9 (Ci), 159.6 (C). Anal. Calcd for C47H73NO8Si: C,
69.85; H, 9.10; N, 1.73. Found: C, 69.82; H, 9.13; N, 1.75.
0
0
4.25. (5S,8S,9S,10R)-1-Benzyl-9-(benzyloxy)-10-hydroxy-8-
[(10E)-9-oxopentadec-1-enyl)]-3,7-dioxa-1-azaspiro[4.5]-
decane-2,6-dione (31)
4.23. (4S)-3-Benzyl-4-[(10R,20R,30S,40E)-20-(benzyloxy)-120,120-
ethylenedioxy-10,30-(isopropylidenedioxy)octadec-40-enyl]-4-
(hydroxymethyl)oxazolidin-2-one (29)
Aq HCl (2 M, 1.56 mL) was added dropwise to a solution of acid 30
(50 mg, 0.07 mmol) in tetrahydrofuran (4.5 mL) and the mixture
was refluxed for 7 h. Then, the mixture was cooled to room temper-
ature and neutralized by cautious addition of satd aq NaHCO3 and
extracted with CH2Cl2 (3 ꢃ 10 mL). The combined organic layers
were dried over Na2SO4, the solvent was evaporated, and the residue
was subjected to flash chromatography through a short silica gel
column (2:1 hexane–EtOAc) to afford 31 mg (72%) of lactone 31 as
A solution of Bu4NF in THF (1 M, 0.14 mL, 0.14 mmol) was
added dropwise to a solution of 28 (0.11 g, 0.14 mmol) in dry
tetrahydrofuran (1.4 mL) that was pre-cooled to 0 °C. The reaction
mixture was stirred for 10 min at 0 °C and then for 20 min at room
temperature. The solvent was evaporated in vacuo and the residue
was partitioned between EtOAc (5 mL) and water (2 mL). The
aqueous phase was extracted with further portions of EtOAc
(2 ꢃ 5 mL). The combined organic layers were dried over Na2SO4
and the solvent was evaporated. Chromatography of the residue
on silica gel (2:1 hexane–EtOAc) afforded 83 mg (88%) of alcohol
a colourless oil: ½a D20
ꢂ
+79.1 (c 0.26, CHCl3). 1H NMR (CDCl3,
600 MHz): d 0.88 (t, J = 6.9 Hz, 3H, CH3), 1.23–1.33 (m, 10H,
5 ꢃ CH2), 1.34–1.41 (m, 2H, CH2), 1.51–1.58 (m, 4H, 2 ꢃ CH2),
2.01–2.11 (m, 2H, 2 ꢃ H-30), 2.26–2.31 (m, 1H, OH), 2.37 (t,
J = 7.2 Hz, 4H, 2 ꢃ CH2), 3.61 (dd, J10,9 = 4.3 Hz, J9,8 = 2.2 Hz, 1H, H-
9), 4.01 (d, JH,H = 16.5 Hz, 1H, NCH2Ph), 4.14 (t, J10,9 = 4.4 Hz,
J10,OH = 4.4 Hz, 1H, H-10), 4.21 (d, JH,H = 10.2 Hz, 1H, OCH2Ph), 4.47
(d, JH,H = 10.2 Hz, 1H, OCH2Ph), 4.56 (d, J4,4 = 11.5 Hz, 1H, H-4), 4.59
(d, J4,4 = 11.5 Hz, 1H, H-4), 5.04 (d, JH,H = 16.5 Hz, 1H, NCH2Ph), 5.16
29 as a colourless oil: ½a D20
ꢂ
+73.5 (c 0.20, CHCl3). 1H NMR (CDCl3,
600 MHz): d 0.88 (t, 3H, J = 6.9 Hz, CH3), 1.23–1.35 (m, 19H,
8 ꢃ CH2, CH3), 1.40 (s, 3H, CH3), 1.55–1.60 (m, 4H, 2 ꢃ CH2),
1.91–2.05 (m, 2H, 2 ꢃ H-60), 2.85 (m, 1H, H-20), 3.69 (m, 2H,
2 ꢃ CH2O), 3.86 (d, J5,5 = 8.6 Hz, 1H, H-5), 3.88–3.93 (m, 5H,
2 ꢃ CH2, H-30), 3.95 (m, 1H, H-10), 4.46 (s, 2H, 2 ꢃ OCH2Ph), 4.55
(d, JH,H = 15.2 Hz, 1H, NCH2Ph), 4.61 (d, JH,H = 15.2 Hz, 1H, NCH2Ph),
0
0
0
0
0
(m, 1H, H-8), 5.63 (tdd, J2 ,1 = 15.3 Hz, J8,1 = 7.9 Hz, J3 ,1 = 1.4 Hz,
0
0
0
0
0
0
0
0
0
0
4.88 (d, J5,5 = 8.6 Hz, 1H, H-5), 5.49 (dd, J5 ,4 = 15.4 Hz, J4 ,3 = 7.2 Hz,
J3 ,1 = 1.4 Hz, 1H, H-10), 5.85 (td, J2 ,1 = 15.3 Hz, J3 ,2 = 6.7 Hz,
1H, H-40), 5.66 (td, J5 ,4 = 15.4 Hz, J6 ,5 = 6.7 Hz, J6 ,5 = 6.7 Hz, 1H, H-
50), 7.27–7.42 (m, 8H, Ph), 7.49–7.53 (m, 2H, Ph). 13C NMR (CDCl3,
150 MHz): d 14.1 (CH3), 19.0 (CH3), 22.6 (CH2), 23.8 (CH2), 23.8
(CH2), 28.8 (CH2), 29.3 (CH2), 29.5 (CH3), 29.6 (CH2), 29.8 (CH2),
31.8 (CH2), 32.3 (CH2), 37.1 (CH2), 37.2 (CH2), 45.7 (CH2), 64.4
(CH2), 64.9 (2 ꢃ CH2), 65.5 (C), 66.1 (CH2), 71.9 (CH), 73.3 (CH),
74.5 (CH2), 75.1 (CH), 99.1 (C), 111.8 (C), 126.9 (CH), 127.6 (CHPh),
127.9 (2 ꢃ CHPh), 128.2 (2 ꢃ CHPh), 128.3 (CHPh), 128.6 (2 ꢃ CHPh),
129.0 (2 ꢃ CHPh), 134.2 (CH), 137.7 (Ci), 138.5 (Ci), 159.2 (C). Anal.
Calcd for C41H59NO8: C, 70.97; H, 8.57; N, 2.02. Found: C, 70.92; H,
8.60; N, 2.05.
J3 ,2 = 6.7 Hz, 1H, H-20), 7.24–7.39 (m, 10H, Ph). 13C NMR (CDCl3,
150 MHz): d 14.0 (CH3), 22.5 (CH2), 23.7 (CH2), 23.8 (CH2), 28.4
(CH2), 28.9 (CH2), 28.9 (CH2), 29.0 (CH2), 31.6 (CH2), 32.2 (CH2),
42.7 (CH2), 42.8 (CH2), 49.1 (CH2), 67.2 (C), 69.6 (CH2), 72.4 (CH),
74.3 (CH2), 77.6 (CH), 80.4 (CH), 123.2 (CH), 126.7 (2 ꢃ CHPh),
127.8 (CHPh), 128.0 (2 ꢃ CHPh), 128.6 (CHPh), 128.7 (2 ꢃ CHPh),
129.2 (2 ꢃ CHPh), 136.2 (Ci), 137.4 (CH), 138.4 (Ci), 159.8 (C), 169.9
(C), 211.6 (C). Anal. Calcd for C36H47NO7: C, 71.38; H, 7.82; N, 2.31.
Found: C, 71.42; H, 7.85; N, 2.27.
0
0
0
0
0
0
0
0
4.26. (4S)-3-Benzyl-4-[(10R,20R,30S,40E)-20-(benzyloxy)-10,30-
dihydroxy-120-oxooctadec-40-enyl]-2-oxooxazolidine-4-
carboxylic acid (32)
4.24. (4S)-3-Benzyl-4-[(10R,20R,30S,40E)-20-(benzyloxy)-120,120-
ethylenedioxy-10,30-(isopropylidenedioxy)octadec-40-enyl]-2-
oxooxazolidine-4-carboxylic acid (30)
Aq NaOH (10%, 1.2 mL) was added dropwise to a solution of lac-
tone 31 (24 mg, 0.04 mmol) in MeOH (1.2 mL) and the reaction
mixture was stirred at 80 °C for 30 min. Then, the mixture was
cooled to room temperature and neutralized with Amberlite IR-
120 (H+). Insoluble materials were removed by filtration, and
Pyridinium dichromate (0.640 g, 1.70 mmol) was added to a
solution of alcohol 29 (76 mg, 0.11 mmol) in dry DMF (0.63 mL).
After stirring at room temperature for 24 h, the reaction mixture

M. Martinková et al. / Carbohydrate Research 345 (2010) 2427–2437
2437
Table 1
Supplementary data
Crystal data and structure refinement parameters for compound 13
13
Complete crystallographic data for the structural analysis have
been deposited with the Cambridge Crystallographic Data Centre,
CCDC No. 738648. These data can be obtained free of charge from
the Director, Cambridge Crystallographic Data Centre, 12 Union
Road, Cambridge, CB2 1EZ, UK (fax: + 44-1223-336033; e-mail:
deposit@ccdc.cam.ac.uk or via: www.ccdc.cam.ac.uk).
Empirical formula
Formula weight
Temperature, T (K)
Wavelength, k (Å)
Crystal system
Space group
C16H21NO8
355.34
293(2)
0.71073
Monoclinic
P21
Unit cell dimensions
a (Å)
b (Å)
6.5654 (4)
14.7939 (10) b = 90.701(6)°
9.2768 (6)
Acknowledgements
c (Å)
V (Å3)
900.97 (10)
The present work was supported by the Grant Agency (Nos. 1/
0100/09, 1/0281/08 and 1/0089/09) of the Ministry of Education,
Slovak Republic. NMR measurements provided by the Slovak
State Programme Project No.2003SP200280203 are gratefully
acknowledged.
Formula per unit cell, Z
2
Dcalcd (g/cm3)
1.310
0.106
376
Absorption coefficient,
F(0 0 0)
l
(mmꢀ1
)
Crystal size (mm)
h Range for data collection (°)
0.5 ꢃ 0.414 ꢃ 0.037
3.10–26.50
Index ranges
ꢀ7 6 h 6 8
ꢀ18 6 k 6 18
ꢀ11 6 l 6 11
3647 (0.0374)
Analytical
References
Independent reflections (Rint)
Absorption correction
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Refinement method
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Full-matrix least-squares on F2
364/1/243
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0.805
Final R indices [I > 2
R indices (all data)
r
(I)]
R1 = 0.0359, wR2 = 0.0571
R1 = 0.0976, wR2 = 0.0655
0.103 and ꢀ0.116
Largest diff. peak and hole (e/Åꢀ3
)
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washed with MeOH, and the solvent was evaporated under re-
duced pressure. The residue was chromatographed through a short
column of silica gel (7:1 CH2Cl2–MeOH) to afford 20 mg (81%) of
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compound 32 as a colourless oil: ½a D20
ꢂ
+49.3 (c 0.27, CH3OH). 1H
NMR (CD3OD, 600 MHz): d 0.88 (t, J = 6.8 Hz, 3H, CH3), 1.24–1.37
(m, 12H, 6 ꢃ CH2), 1.48–1.55 (m, 4H, 2 ꢃ CH2), 1.93–1.99 (m, 2H,
2 ꢃ H-60), 2.41 (t, J = 7.3 Hz, 4H, 2 ꢃ CH2), 3.09 (m, 1H, H-20), 3.91
(m, 1H, H-30), 4.13 (d, JH,H = 15.4 Hz, 1H, NCH2Ph), 4.18 (m, 1H,
H-10), 4.39–4.43 (m, 2H, H5, OCH2Ph), 4.68–4.72 (m, 1H, OCH2Ph),
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Synlett 2001, 904–906; (b) Trost, B. M.; Lee, C. J. Am. Chem. Soc. 2001, 123,
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2008, 64, 9521–9527; (e) Yamanaka, H.; Sato, K.; Sato, H.; Iida, M.; Oishi, T.;
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0
0
4.80 (d, JH,H = 15.4 Hz, 1H, NCH2Ph), 5.02 (dd, J5 ,4 = 15.4 Hz,
J4 ,3 = 7.1 Hz, 1H, H-40), 5.05 (d, J5,5 = 8.3 Hz, 1H, H-5), 5.49–5.56
(m, 1H, H-50), 7.22–7.25 (m, 1H, Ph), 7.26–7.32 (m, 3H, Ph), 7.32–
7.36 (m, 4H, Ph), 7.40–7.43 (m, 2H, Ph). 13C NMR (CD3OD,
150 MHz): d 14.4 (CH3), 23.6 (CH2), 24.9 (CH2), 24.9 (CH2), 30.0
(CH2), 30.1 (CH2), 30.2 (CH2), 30.2 (CH2), 32.8 (CH2), 33.3 (CH2),
43.5 (CH2), 43.5 (CH2), 48.7 (CH2), 69.6 (CH2), 71.6 (C), 72.7 (CH),
75.9 (CH2), 76.4 (CH), 81.0 (CH), 128.7 (CHPh), 129.0 (CHPh), 129.3
(2 ꢃ CHPh), 129.4 (2 ꢃ CHPh), 129.9 (2 ꢃ CHPh), 130.2 (2 ꢃ CHPh),
131.2 (CH), 133.8 (CH), 139.5 (Ci), 139.6 (Ci), 162.3 (C), 177.5 (C),
214.3 (C). Anal. Calcd for C36H49NO8: C, 69.32; H, 7.92; N, 2.25.
Found: C, 69.30; H, 7.95; N, 2.20.
0
0
8. (a) Gonda, J.; Bednáriková, M. Tetrahedron Lett. 1997, 38, 5569–5572; (b)
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Asymmetry 2006, 17, 1875–1882; (d) Martinková, M.; Gonda, J.;
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ˇ
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ˇ
(b) Gajdošíková, E.; Martinková, M.; Gonda, J.; Conka, P. Molecules 2008, 13,
2837–2847.
ˇ
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Diffraction XCalibur2 CCD diffractometer using Mo K
a radiation
(k = 0.71073 Å). Selected crystallographic and other relevant data
for the compound 13 are listed in Table 1. The structure was solved
by direct methods.17 All non-hydrogen atoms were refined aniso-
tropically by full-matrix least-squares calculations based on F2.17
All hydrogen atoms were included in calculated positions as riding
18
atoms, with SHELXL9717 defaults. PLATON programme was used for
structure analysis and molecular and crystal structure drawings
preparation.