Synthesis of novel types of divalent saccharide structures by a ketene acetal Claisen rearrangement

Article abstract of DOI:10.1016/j.tetasy.2004.12.001

A simple allyl uronate was rearranged to give the branched product, which in turn could be transformed into a spiro-annellated bicyclic compound. More complex allyl uronates of d-and l-arabinose were rearranged to give novel methylene-bridged dimeric sacc

Full text of DOI:10.1016/j.tetasy.2004.12.001

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 569–576
Synthesis of novel types of divalent saccharide structures by
a ketene acetal Claisen rearrangement
Barbara Werschkun and Joachim Thiem*
Institut fu¨r Organische Chemie der Universita¨t, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany
Received 16 November 2004; accepted 1 December 2004
Available online 13 January 2005
Dedicated to Prof. Stephen J. Angyal, Sydney, on the occasion of his 90th birthday in recognition of his eminent
contribution to carbohydrate chemistry
Abstract—A simple allyl uronate was rearranged to give the branched product, which in turn could be transformed into a spiro-
annellated bicyclic compound. More complex allyl uronates of D-and L-arabinose were rearranged to give novel methylene-bridged
dimeric saccharide structures.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction
branched urinate 25,6 could be obtained by enolization
of the allyl ester easily prepared from the corresponding
uronic acid 14 (Scheme 1). Prior to further processing of
the branching side chain into a second saccharide moi-
ety, the uronate carbonyl group was reduced and the
resulting alcohol acetylated by standard synthetic steps
to obtain lyxofuranoside 3. To transform the terminal
double bond into the desired hydroxyaldehyde function,
the synthetic strategy ingeniously elaborated during the
total synthesis of L-hexoses7,8 was adopted and simpli-
fied with respect to the far less demanding present case.
Since in these initial studies there was no focus on
stereochemistry, epoxidation was easily carried out with
m-chloroperbenzoic acid to give a high yield of the dia-
stereomeric epoxide mixture 4. Base induced epoxide
opening with thiophenol to 5 enabled introduction of
a masked aldehyde function via Pummerer rearrange-
ment9 of the corresponding sulfoxide, to give a mixture
of four stereoisomers of acetoxy thioacetals 6. Base cat-
alyzed deacetylation proceeded smoothly under the re-
lease of the aldehyde and, subsequently, spontaneous
formation of a cyclic hemiacetal moiety, to result in
the bicyclic structure 7 containing two anomeric centres.
The general feasibility of the overall process was thus
demonstrated, with future work directed towards the
synthesis of fully oxygenated and stereochemically pure
derivatives.
Aiming at the specific manipulation of biologically
important carbohydrate recognition and bindings sites,
considerable efforts have been directed towards the de-
sign and chemical synthesis of structural mimetics for
significant naturally occurring saccharides. In order to
inhibit reaction pathways proceeding subsequent to
binding and to generally minimize biological degrada-
tion, a particularly high value is attributed to the unique
chemical stability of C–C connected derivatives, as it is
reflected by the rapidly growing activities in the field
of C-glycoside synthesis.1 An approach to enhance bind-
ing affinity by displaying a crucial structural unit more
than once within the same molecule has recently lead
to the development of a variety of oligovalent glyco-
structures.2,3 In our contribution, a combination of both
features was sought to be realized by the synthesis of
divalent molecules, which should be tied together by a
carbon–carbon bond.
2. Results and discussion
C–C bond formation as a key synthetic step can be
achieved by means of ketene acetal Claisen rearrange-
ment, which has previously been applied successfully
to uronic acid derived starting materials.4 Thus, C-allyl
The above described procedure employed a ketene
acetal rearrangement starting from a simple allyl ester
at the beginning of the synthetic sequence followed by
*
Corresponding author. Tel.: +49 40 42838 4241; fax: +49 40 42838
4325; e-mail: joachim.thiem@chemie.uni-hamburg.de
0957-4166/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2004.12.001

570
B. Werschkun, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 569–576
AcO
O
HO
MeO
O
O
O
O
i, ii
iii
O
O
O
O
O
O
OBn
OBn
OBn
3
1
2
AcO
O
AcO
O
O
v
iv
O
O
O
O
OBn
OBn
PhS
4
5
OAc
AcO
OAc
O
O
O
vi
PhS
vii
HO
O
O
O
O
OBn
OBn
HO
6
7
OAc
Scheme 1. Reagents and conditions: (i) (COCl)2, cat. DMF, PhH, 0 ꢁC to rt; DMAP, CH2@CHCH2OH, CH2Cl2, 0 ꢁC to rt; 94%; (ii) TMSCl, LDA,
THF–HMPA, ꢀ100 ꢁC to rt; TBAF, THF; TMSCHN2, PhH–MeOH, 43%; (iii) LAH, THF, reflux; Ac2O, Py, 83%; (iv) MCPBA, CH2Cl2, 87%; (v)
PhSH, ButOK, ButOH–DMF, reflux; Ac2O, Py, 41%; (vi) MCPBA, CH2Cl2, ꢀ78 ꢁC; NaOAc, Ac2O, reflux, 66%; (vii) Na2CO3, MeOH, 87%.
several further manipulations to obtain the complex
disaccharide structure. Our second approach used the
reverse strategy by linking the complete second saccha-
ride unit into the urinate precursor and performing an
enolization and Claisen rearrangement at a late stage
of the overall process (Scheme 2). Starting from the
corresponding 3,4-acetonide,10 the suitably protected
D-arabinopyranoside 8 was prepared via regioselective
opening11 of a stannylene intermediate. Swern oxida-
tion12 followed by Wittig reaction of ketone 9 gave the
exocyclic alkene 10, from which the allylic hydroxyl
function could be selectively released by palladium cata-
lyzed deallylation.13 The resulting alcohol 11 was
reacted with the same uronic acid 1 employed in the pre-
vious synthesis to give allyl ester 12. After enolization
and silylation to the corresponding ketene acetal, a 1:1
mixture of both epimeric rearrangement products 13a
and 13b was formed in a total yield of only 15%. The
lack of stereodiscrimination during sigmatropic rear-
rangement in the present case was rather unexpected,
as results previously reported,5,6 indicated a clear prefer-
ence of the bond forming process to occur trans to the
furanoside isoprop- ylidenedioxy moiety.
To rationalize the observed stereochemical ambiguity,
as well as the modest total yield, different stereoelec-
OMe
OBn
O
OBn
MeO
O
MeO
O
O
O
OMe
OBn
OMe
OBn
O
O
O
O
O
OBn
O
O
O
i
iv
v
O
O
+
OAll
O
O
OR
X
HO
OBn
OBn
OBn
MeO
O
MeO
8
12
13a
13b
9: X = O ; R =All
ii
iii
10: X = CH2 ; R = All
11: X = CH2 ; R = H
OMe
O
HO
AllO
MeO
O
O
X
O
O
BnO
O
O
O
BnO
OBn
O
ix
vi
x
OMe
O
O
RO
O
O
O
+
OBn
BnO
BnO
O
O
OMe
OMe
OBn
BnO
O
MeO
O
14
18
19a
19b
OMe
15: X = O ; R =All
vii
viii
16: X = CH2 ; R = All
17: X = CH2 ; R = H
Scheme 2. All = allyl. Reagents and conditions: (i) (COCl)2, DMSO, CH2Cl2, ꢀ40 ꢁC; NEt3, 68%; (ii) Ph3PCH2, Et2O, 50%; (iii) 10% Pd–C, TsOH,
MeOH, reflux, 72%; (iv) 1, DCC, DMAP, CH2Cl2, 0 ꢁC to rt, 70%; (v) TMSCl, LDA, THF–HMPA, ꢀ100 ꢁC to rt; TBAF, THF; TMSCHN2, PhH–
MeOH, 15%; (vi) same as (i) 56%; (vii) same as (ii), 40%; (viii) same as (iii), 61%; (ix) same as (iv), 91%; (x) same as (v), 40%.

B. Werschkun, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 569–576
571
20
578
tronic influences may be supposed to direct in opposite
ways. Apart from steric crowding, the transition state
geometry is of dominant importance. Only very recently
for a closely related structure of the starting material6
could this be proven to predominantly adopt a chair-like
conformation. The number of possible transition state
structures in this case is restricted by the allyloxy moiety
being partially embedded in a pyranoside ring, and
hence the configuration at its connecting 3-position
could play an important role. An obvious approach to
further investigate this matter was to repeat the same
starting material synthesis within the oppositely configu-
rated L-arabino series. Thus, the corresponding aceto-
nide precursor14 was likewise transformed into
hydroxyl compound 14, oxidized to ketone 15 and the
resultant Wittig product 16 deallylated to alcohol 17,
esterification of which with uronic acid 1 gave allyl ester
18, suitable for another ketene acetal Claisen rearrange-
ment. Subsequently, the epimeric products 19a and 19b
were obtained in a significantly increased total yield of
40%. With respect to stereoselectivity, though, only very
little improvement could be observed; the D-lyxo isomer
19a being formed in a slightly larger amount. Elucida-
tion of the nature and extent of the respective influences
leading to this unexpected behaviour remains a task to
be addressed in future research in our laboratories, as
well as the possible elaboration of the obtained novel
dimers into fully oxygenated disaccharide structures.
2 as colourless syrup (11 mg, 83%); ½aꢁ ¼ þ45:5 (c
1.0, CHCl3); C20H26O6 (362.4); 1H NMR (400 MHz,
CDCl3): d 1.24, 1.50 (2 · s, 2 · 3H, 2 · Me), 2.05 (s,
3H, OAc), 2.38, 2.56 (2 · dd, 2 · 1H, CH2), 4.08, 4.22,
4.41, 4.71 (4 · d, 4 · 1H, H-5a, H-5b, benzyl–OCH2,
J5a,5b = 11.7 Hz) 4.53, 4.74 (2 · d, 2 · 1H, H-2, H-3,
J2,3 = 6.1 Hz), 5.05 (m, 2H, @CH2), 5.11 (s, 1H, H-1),
5.69–5.79 (m, 1H, @CH–) 7.22–7.28 (m, 5H, aryl), 13C
NMR (100 MHz, CDCl3): d 19.93, 23.79, 25.09 (3C,
3 · Me), 39.28 (1C, CH2), 63.35, 68.72 (2C, C-5, ben-
zyl–OCH2), 82.63, 85.40 (2C, C-2, C-3), 86.61 (1C, C-
4), 106.50 (1C, C-1), 111.89 (1C, iPrdn), 117.95 (1C,
@CH2), 126.80–136.30 (7C, @CH–, aryl), 169.52 (1C,
acetyl–CO2).
3.3. Benzyl 5-O-acetyl-2,3-O-isopropylidene-4-C-
(2,3-epoxypropyl)-a-D-lyxofuranoside 4
A solution of 3 (109 mg, 0.3 mmol) in anhydrous dichlo-
romethane (5 mL) was stirred with 4-chloroperbenzoic
acid (87 mg, 0.5 mmol) at room temperature. For
work-up the solution was washed with saturated sodium
hydrogencarbonate, concentrated under reduced pres-
sure to dryness and the remainder purified by column
chromatography (petroleum ether/ethyl acetate 10:1)
to give the diastereomeric mixture (ca. 1:1) of 4 as
colourless crystals (98 mg, 87%); C20H26O7 (378.4), EI:
m/z = 363 (MꢀMe); 1H NMR (400 MHz, CDCl3): d
1.25, 1.42 (2 · s, 2 · 6H, 4 · Me), 1.61, 1.75 (2 · dd,
2 · 1H, 2 · H-10, J1 ,1 = 14.5, J1 ,2 = 5.1, 8.1 Hz), 2.04,
2.05 (2 · s, 2 · 3H, 2 · OAc), 2.11, 2.18 (2 · dd,
2 · 1H, 2 · H-10), 2.35, 2.39 (2 · dd, 2 · 1H, 2 · H-30,
0
0
0
0
3. Experimental
3.1. General
J3 ,3 = 4.9 Hz), 2.67, 2.73 (2 · dd t, 2 · 1H, 2 · H-30),
0
0
2.96, 3.04 (2 · m, 2 · 1H, 2 · H-20, J2 ,3 = 2.5, 4.6 Hz),
0
0
Solvents were purified and dried according to standard
procedures. Petroleum ether used refers to bp 50–
70 ꢁC. TLC was performed on silica gel 60-coated alu-
minium sheets (Merck or Macherey-Nagel), with detec-
tion by UV at 254 nm and by heating with H2SO4 (5% in
EtOH). Flash chromatography was carried out on silica
gel 60 (0.04–0.063 mm; Merck, Macherey-Nagel or
ICN). NMR spectra were recorded on a Bruker
AMX-400 NMR spectrometer (1H: 400 MHz; 13C:
100 MHz) with TMS as internal standard. Melting
points were determined on a Leitz apparatus and are
uncorrected. The optical rotations were measured on a
Perkin-Elmer 243 or 341 polarimeter at 20 ꢁC.
4.16, 4.26, 4.29, 4.39, 4.43, 4.44, 4.67, 4.70 (8 · d,
8 · 1H,
2 · H-5a,
2 · H-5b,
2 · benzyl–OCH2,
0
0
J5a ,5b = 11.7 Hz) 4.54, 4.68, 4.73, 4.75 (4 · d, 4 · 1H,
2 · H-2, 2 · H-3, J2,3 = 5.6 Hz), 5.11, 5.13 (2 · s,
2 · 1H, 2 · H-1), 7.20–7.30 (m, 10H, aryl); 13C NMR
(100 MHz, CDCl3): d 19.93, 19.96 (2C, 2 · acetyl–Me),
23.81, 25.09, 25.11 (4C, 4 · iPrdn–Me), 37.81, 37.86
(2C, 2 · C-10), 45.36, 46.32 (2C, 2 · C-30), 47.22, 47.26
(2C, 2 · C-20), 63.61, 63.78, 68.75, 68.98 (4C, 2 · C-5,
2 · benzyl–OCH2), 82.88, 82.98, 85.39 (4C, 2 · C-2,
2 · C-3), 85.92, 86.35 (2C, 2 · C-4), 106.70, 106.79
(2C, 2 · C-1), 112.02, 112.12 (2C, 2 · iPrdn), 126.75–
136.18 (12C, aryl), 169.55 (2C, 2 · acetyl–CO2).
3.2. Benzyl 5-O-acetyl-2,3-O-isopropylidene-4-C-
(2-propenyl)-a-D-lyxofuranoside 3
3.4. Benzyl 5-O-acetyl-2,3-O-isopropylidene-4-C-
(2-acetyloxy-3-phenylthiopropyl)-a-D-lyxofuranoside 5
A solution of methyl (benzyl-2,3-O-isopropylidene-4-C-
(2-propenyl)-a-D-lyxofuranoside)-uronate 25,6 (361 mg,
1.04 mmol) in anhydrous THF (5 mL) was added drop-
wise to a suspension of lithium aluminium hydride
(20 mg, 0.5 mmol) in THF (5 mL). The mixture was re-
fluxed for 1 h, after cooling diluted with ethyl acetate,
excessive hydride hydrolyzed with water and the precip-
itate dissolved with 2 M sulfuric acid. The organic phase
was washed with saturated sodium chloride solution and
concentrated to dryness. The residue was acetylated in
anhydrous pyridine (10 mL) with acetic anhydride
(5 mL) and worked up by standard procedure to give
A solution of 4 (89 mg, 235 lmol) in tert-butanol (2 mL)
was treated with a solution of thiophenol (30 lL,
0.3 mmol) and potassium tert-butylate (45 mg,
0.4 mmol) in dimethylformamide (1 mL) and then
heated under reflux for 12 h. For work-up the mixture
was diluted with water, the organic phase washed with
saturated sodium chloride solution and dried under re-
duced pressure. The remainder was acetylated with pyr-
idine (5 mL) and acetic acid anhydride (5 mL) at room
temperature and after work-up purified by column chro-
matography (petroleum ether/ethyl acetate 5:1) to give
the diastereomeric mixture 5 (51 mg, 41%) as a yellow

572
B. Werschkun, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 569–576
syrup; C28H34O8S (530.6); EI: m/z = 530 (M+); 1H NMR
(400 MHz, CDCl3): d 1.24, 1.25, 1.30, 1.43 (4 · s, 4 · 3H,
4 · Me), 1.88, 1.89, 2.03, 2.05 (4 · s, 4 · 3H, 4 · OAc),
2.03, 2.29 (2 · m, 1H, 3H, 2 · CH2), 2.96, 3.08, 3.20
(3 · m, 2H, 1H, 1H, 2 · SCH2), 4.01, 4.09, 4.18, 4.23
(4 · d, 4 · 1H, 2 · H-5a, 2 · H-5b, J5a,5b = 11.7 Hz),
4.47 (d, 2H, OCH2), 4.49, 4.61, 4.74, 4.77 (4 · d,
4 · 1H, 2 · H-2, 2 · H-3, J2,3 = 5.9 Hz), 4.65, 4.79
(2 · d, 2 · 1H, OCH2), 5.11, 5.16 (2 · s, 2 · 1H, 2 · H-
1, J1,2 = 0 Hz), 5.13, 5.28 (2 · m, 2 · 1H, 2 · H-20),
7.15–7.40 (m, 20H, aryl); 13C NMR (100 MHz, CDCl3):
d 20.84, 20.86, 20.93, 20.98 (4C, 4 · acetyl–Me), 24.54,
24.88, 25.92, 26.10 (4C, 4 · iPrdn–Me), 37.98, 38.38
(2C, 2 · C-l0), 63.67, 64.90 (2C, 2 · C-30), 69.42, 69.51,
69.59, 70.02 (4C, 2 · C-5, 2 · benzyl–OCH2), 77.20,
83.74, 84.40, 86.29, 86.34 (6C, 2 · C-2, 2 · C-3, 2 · C-
20), 86.68, 87.08 (2C, 2 · C-4) 107.23, 107.48 (2C,
2 · C-1), 113.03 (2C, 2 · iPrdn), 126.30–136.00 (24C,
aryl).
perature. After deacetylation, the solution was neutral-
ized with Amberlite 120 H+, the solution taken to
dryness under reduced pressure and the residue purified
by column chromatography (petroleum ether/ethyl ace-
tate 2:1) to give the diastereomeric mixture 7 as yellow
syrup (20 mg, 87%); C18H24O7 (352.4); 1H NMR
(400 MHz, CDCl3): d 1.18, 1.23, 1.39 (iPrdn–Me),
1.66, 1.82, 2.09, 2.39 (H-10), 3.63 (H-9), 3.93, 4.09 (H-
6), 4.42 (H-3/H-4, benzyl–OCH2), 4.65 (H-8), 4.72 (H-
3/H-4), 4.78 (benzyl–OCH2), 5.13, 5.15 (H-2); 13C
NMR (100 MHz, CDCl3): d 23.53, 24.84 (iPrdn–Me),
36.91 (C-10), 62.97, 66.22, 67.41, 69.02, 69.13 (C-6, C-
9, benzyl–OCH2), 82.76, 83.23, 83.62, 84.91 (C-3, C-4,
C-5), 94.18 (C-8), 106.22 (C-2), 112.04 (iPrdn), 126.95–
127.55 (aryl).
3.7. Methyl 3-O-allyl-2-O-benzyl-b-D-arabinopyranoside
8
A solution of methyl 2-O-benzyl-3,4-O-isopropylidene-
b-D-arabinopyranoside10 (1.76 g, 6 mmol) in aqueous
acetic acid (80%, 6 mL) was stirred at room temperature
overnight and then co-distilled with toluene under re-
duced pressure to dryness. The residue was dissolved
in anhydrous toluene (35 mL) and heated with dibutyl-
tinoxide (1.78 g, 7.1 mmol) under reflux. When a clear
solution formed, the mixture was taken to dryness and
the residue together with caesium fluoride (1.27 g,
8.4 mmol) suspended in anhydrous dimethylformamide
(35 mL) and stirred with allylbromide (1.1 mL,
13 mmol) at room temperature. For work-up, the mix-
ture was diluted with ethyl acetate, washed with water,
dried, concentrated and the remainder purified by col-
umn chromatography (petroleum ether/ethyl acetate
3.5. Benzyl 5-O-acetyl-2,3-O-isopropylidene-4-C-(2,3-
diacetyloxy-3-phenylthiopropyl)-a-D-lyxofuranoside 6
A solution of 5 (48 mg, 90 lmol) in anhydrous dichlo-
romethane (2 mL) was treated at ꢀ78 ꢁC with 3-chloro-
perbenzoic acid (80%, 20 mg, ca. 90 lmol) in
dichloromethane (0.2 mL). After 5 min quenching was
done with 1 M aqueous sodium hydroxide. The mixture
was diluted with dichloromethane, and the organic
phase washed with 1 M aqueous sodium hydroxide,
water and saturated sodium chloride solution. The resi-
due obtained after concentration to dryness was dis-
solved in acetic anhydride (1 mL), after which sodium
acetate (45 mg, 0.5 mmol) was added and then heated
to reflux overnight. The mixture was co-distilled with
toluene to dryness, the residue suspended in dichloro-
methane, filtered and the filtrate washed with saturated
sodium hydrogen carbonate solution, water and saturated
sodium chloride solution. The remainder was taken to
dryness under diminished pressure and the residue puri-
fied by column chromatography (petroleum ether/ethyl
acetate 5:1) to give the diastereomeric mixture 6 as
yellow syrup (35 mg, 66%); C30H36O10S (588.7); EI:
m/z = 573 (MꢀMe); 1H NMR (400 MHz, CDCl3): d
1.24–1.46 (8s, 8 · 3H, 8 · Me), 1.97–2.12 (12 · s,
12 · 3H, 12 · OAc), 2.22–2.45 (m, 8H, 4 · CH2), 4.04–
4.89 (24H, 4 · OCH2, 4 · H-2, 4 · H-3, 4 · H-5a,
4 · H-5b), 5.12, 5.15, 5.17, 5.19 (4 · s, 4 · 1H, 4 · H-
1), 5.36, 5.44, 5.54 (3 · m, 1H, 1H, 2H, 4 · H-20), 6.04,
6.08, 6.20, 6.22 (4 · d, 4 · 1H, 4 · H-30), 7.26–7.50
(aryl); 13C NMR (100 MHz, CDCl3): d 20.80–21.05
(acetyl–Me), 24.64–26.06 (iPrdn–Me), 34.10, 34.37 (C-
10), 62.89, 63.57, 63.83, 68.46, 69.04, 69.10 (C-5, ben-
zyl–OCH2), 69.12, 69.62, 81.60–86.30 (C-2, C-3, C-20,
C-30), 86.35–86.55 (C-4), 107.28, 107.39, 107.44 (C-1),
113.03, 113.10, 113.21 (iPrdn), 127.52–133.77 (aryl).
10:1 to 2:1) to give 8 as a colourless syrup (1.3 g,
20
73%); ½aꢁ ¼ ꢀ158:8 (c 2.0, CHCl3); C16H22O5 (294.3);
D
EI: m/z = 294 (M+); 1H NMR (400 MHz, CDCl3): d
3.38 (s, 3H, OMe), 3.67–3.77 (m, 4H, H-2, H-3, H-5a,
H-5b), 4.01 (br s, 1H, H-4), 4.17–4.27 (m, 2H, allyl–
OCH2), 4.64 (d, 1H, H-1, J1,2 = 1.5 Hz), 4.65, 4.78
(2 · d, 2 · 1H, benzyl–OCH2), 5.20, 5.31 (2 · m,
2 · 1H, @CH2), 5.90–5.99 (m, 1H, @CH–), 7.27–7.37
(m, 5H, aryl); 13C NMR (100 MHz, CDCl3): d 55.44
(1C, OMe), 61.44, 71.57, 73.51 (3C, C-5, allyl–OCH2,
benzyl–OCH2), 67.76, 75.65, 76.65 (3C, C-2, C-3, C-4),
99.12 (1C, C-1), 117.27 (1C, @CH2), 127.78–138.46
(7C, @CH–, aryl).
3.8. Methyl 3-O-allyl-2-O-benzyl-b-D-threo-pent-4-ulo-
pyranoside 9
A solution of oxalyl chloride (1 mL, 11.3 mmol) in
anhydrous dichloromethane (10 mL) was cooled to
ꢀ40 ꢁC under argon and then treated with anhydrous
dimethylsulfoxide (1.35 mL, 19 mmol). Compound 8
(1.3 g, 4.4 mmol) dissolved in dichloromethane (1 mL)
was added over 6 h at ꢀ40 ꢁC with stirring. For work-
up the mixture was stirred with triethylamine (7 mL)
for 30 min at room temperature, after which the mixture
was poured into ice water and extracted with ethyl
acetate. The organic phase was dried under reduced
pressure and the remainder purified by column chroma-
tography (petroleum ether/ethyl acetate 3:1 + 5% tri-
3.6. (2S,3S,4R,5R)-2-Benzyloxy-8,9-dihydroxy-3,4-iso-
propylidenedioxy-1,7-dioxa-spiro[4.5]-decane 7
A solution of compound 6 (30 mg, 0.05 mmol) in meth-
anol (1 mL) was treated with sodium carbonate (13 mg,
0.13 mmol) at 0 ꢁC with gradual warming to room tem-

B. Werschkun, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 569–576
573
ethylamine) to give compound 9 as a colourless syrup
J5a,5b = 12.2 Hz), 4.52 (d, 1H, H-3), 4.69 (s, 2H,
OCH2), 4.71 (d, 1H, H-1, J1,2 = 3.4 Hz), 5.00, 5.23
(2 · s, 2 · 1H, @CH2), 7.31–7.37 (m, 5H, aryl); 13C
NMR (100 MHz, CDCl3): d 55.45 (1C, OMe), 63.32,
73.01 (2C, C-5, OCH2) 69.58, 82.64 (2C, C-2, C-3),
98.43 (1C, C-1), 108.60 (1C, @CH2), 128.11–137.93
(6C, aryl), 142.88 (1C, C-4).
20
(826 mg, 68%); ½aꢁ ¼ ꢀ160:2 (c 2.0, CHCl3);
D
C16H20O5 (292.3); EI: m/z = 292 (M+); 1H NMR
(400 MHz, CDCl3): d 3.46 (s, 3H, OMe), 3.73 (dd, 1H,
H-2, J2,3 = 10.0 Hz), 3.86, 4.01 (2 · d, 2 · 1H, H-5a,
H-5b, J5a,5b = 14.8 Hz), 4.17–4.22, 4.40–4.45 (2 · m,
2 · 1H, allyl–OCH2), 4.33 (d, 1H, H-3), 4.68, 4.86
(2 · d, 2 · 1H, benzyl–OCH2), 4.74 (d, 1H, H-1,
J1,2 = 3.4 Hz), 5.21, 5.34 (2 · m, 2 · 1H, @CH2), 5.92–
6.02 (m, 1H, @CH–), 7.27–7.37 (m, 5H, aryl); 13C
NMR (100 MHz, CDCl3): d 56.12 (1C, OMe), 66.05,
73.58, 74.10 (3C, 3 · OCH2), 79.60, 81.87 (2C, C-2, C-
3), 98.88 (1C, C-1), 117.71 (1C @CH2), 127.53–137.88
(7C, @CH–, aryl), 203.30 (1C, C-4).
3.11. Methyl 3-O-allyl-2-O-benzyl-b-L-arabinopyranoside
14
The synthesis is analogous to that of compound 8 by
employing methyl-2-O-benzyl-3,4-O-isopropylidene-b-
arabinopyranoside14 (1.2 g, 4 mmol), aqueous acetic
acid (80%, 5 mL), dibutyltinoxide (1.25 g, 5 mmol) and
toluene (40 mL), dimethylformamide (40 mL), caesium
fluoride (870 mg, 5.8 mmol) and allylbromide
(0.76 mL, 9 mmol). Column chromatography (petro-
3.9. Methyl 3-O-allyl-2-O-benzyl-4-deoxy-4-C-methyl-
ene-b-D-threo-pentopyranoside 10
A solution of methyltriphenylphosphoniumbromide
(330 mg, 0.9 mmol) in anhydrous diethyl ether (3 mL)
was treated under argon with n-butyllithium in hexane
(1.6 M, 0.6 mL) to form under stirring a clear orange
solution within 1 h at room temperature. After dropwise
addition of a solution of 9 (180 mg, 0.6 mmol) in diethyl
ether (1.5 mL), stirring was continued for 1 h. For work-
up the formed viscous suspension was treated with water
and extracted with ethyl acetate. The organic phase was
taken to dryness under diminished pressure and the res-
idue purified by column chromatography (petroleum
leum ether/ethyl acetate 5:1); yield (555 mg, 45%);
20
D
1
colourless syrup; ½aꢁ ¼ þ67:7 (c 1.0, CHCl3);
C16H22O5 (294.3); H NMR (400 MHz, CDCl3): 3.31
(s, 3H, OMe), 3.63–3.71 (m, 4H, H-2, H-3, H-5a, H-
5b), 3.94 (m, 1H, H-4), 4.10–4.17 (m, 2H, allyl–OCH2)
4.57 (d, 1H, H-1, J1,2 = 4.1 Hz), 4.59, 4.72 (2 · d,
2 · 1H, benzyl–OCH2), 5.13, 5.24 (2 · m, 2 · 1H,
@CH2), 5.80–5.94 (m, 1H, @CH–), 7.19–7.30 (m, 5H,
aryl); 13C NMR (100 MHz, CDCl3): d 54.42 (1C,
OMe), 60.39, 70.53 72.48 (3C, C-5, allyl–OCH2, ben-
zyl–OCH2), 66.71, 74.57, 75.60 (3C, C-2, C-3, C-4),
98.07 (1C, C-1), 116.25 (1C, @CH2), 126.60–137.41
(7C, @CH–, aryl).
ether/ethyl acetate 10:1) to give 10 as a colourless syrup
20
(88 mg, 50%); ½aꢁ ¼ ꢀ91:8 (c 2.0, CHCl3); C17H22O4
D
(290.4); EI: m/z = 290 (M+); 1H NMR (400 MHz,
CDCl3): d 3.41 (s, 3H, OMe), 3.42 (dd, 1H, H-2,
J2,3 = 9.0 Hz), 3.89 (d, 1H, H-5a, J5a,5b = 12.2 Hz),
4.19–4.26 (m, 4H, H-3, H-5b, allyl–OCH2), 4.65 (d,
1H, H-1, J1,2 = 3.9 Hz), 4.67, 4.84 (2 · d, 2 · 1H, ben-
zyl–OCH2), 5.00, 5.20 (2 · s, 2 · 1H, @CH2), 5.18,
5.33 (2 · m, 2 · 1H, @CH2), 5.92–6.02 (m, 1H, @CH–),
7.25–7.38 (m, 5H, aryl); 13C NMR (100 MHz, CDCl3):
d 55.48 (1C, OMe), 63.67, 72.60, 73.67 (3C, C-5,
allyl–OCH2, benzyl–OCH2), 78.24, 81.28 (2C, C-2,
C-3), 99.76 (1C, C-1), 109.79 (1C @CH2), 116.73
(1C, @CH2), 127.73–138.52 (7C, @CH–, aryl), 142.48
(1C, C-4).
3.12. Methyl 3-O-allyl-2-O-benzyl-b-L-threo-pent-4-ulo-
pyranoside 15
The preparation was done analogously to that of com-
pound
9 by employing compound 14 (536 mg,
1.8 mmol) in dichloromethane (0.5 mL); dichlormethane
(4 mL), dimethylsulfoxide (0.54 mL, 7.6 mmol) and
oxalylchloride (0.4 mL, 4.6 mmol); triethylamine
(2.7 mL); column chromatography (petroleum ether/
ethyl acetate 3:1 + 5% triethylamine); yield (300 mg,
20
D
56%) colourless syrup; ½aꢁ ¼ þ15:3 (c 0.2, CHCl3);
1
C16H20O5 (292.3); H NMR (400 MHz, CDCl3): d 3.47
(s, 3H, OMe), 3.73 (dd, 1H, H-2, J2,3 = 10.2 Hz), 3.87
(d, 1H, H-5a, J5a,5b = 14.8 Hz), 4.11 (d, 1H, H-5b),
4.18–4.23, 4.40–4.45 (2 · m, 2 · 1H, allyl–OCH2), 4.33
(d, 1H, H-3), 4.69, 4.87 (2 · d, 2 · 1H, benzyl–OCH2),
4.74 (d, 1H, H-1, J1,2 = 3.4 Hz), 5.21, 5.34 (2 · m,
2 · 1H, @CH2), 5.93–6.02 (m, 1H, @CH–), 7.28–7.38
(m, 5H, aryl); 13C NMR (100 MHz, CDCl3): d 56.57
(1C, OMe), 66.48, 74.04 74.38 (3 C, C-5, allyl–OCH2,
benzyl–OCH2) 79.99, 82.31 (2C, C-2, C-3), 99.31 (1C,
C-1), 118.20 (1C, @CH2), 128.42–138.26 (7C, @CH–,
aryl), 203.80 (1C, C-4).
3.10. Methyl 2-O-benzyl-4-deoxy-4-C-methylene-b-D-
threo-pentopyranoside 11
A solution of 10 (384 mg, 1.3 mmol) in methanol
(70 mL) was treated with 4-toluenesulfonic acid
(200 mg, 1.1 mmol) and palladium/charcoal (10%,
530 mg) and heated under reflux. After complete turn-
over, saturated sodium hydrogen carbonate solution
was added, filtered and the filtrate extracted with dichlo-
romethane. The organic phase was washed with satu-
rated sodium hydrogen carbonate solution and water
and then taken to dryness under reduced pressure. The
remainder was purified by column chromatography
3.13. Methyl 3-O-allyl-2-O-benzyl-4-deoxy-4-C-methyl-
ene-b-L-threo-pentopyranoside 16
(petroleum ether/ethyl acetate 10:1 to 5:1) to give 11 as
a
(c 1.0, CHCl3); C14H18O4 (250.3); H NMR (400 MHz,
CDCl3): d 3.32 (dd, 1H, H-2, J2,3 = 9.7 Hz), 3.38 (s,
3H, OMe), 3.89, 4.24 (2 · d, 2 · 1H, H-5a, H-5b,
20
D
colourless syrup (236 mg, 72%); ½aꢁ ¼ ꢀ118:5
The synthesis is analogous to that of compound 10. Em-
ployed are compound 15 (292 mg, 1 mmol) in diethyl
ether (1 mL); methyltriphenylphosphoniumbromide
(526 mg, 1.5 mmol) in diethyl ether (5 mL), and
1

574
B. Werschkun, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 569–576
n-butyllithium in hexane (1.6 M, 1 mL); column chro-
matography (petroleum ether/ethyl acetate 10:1), yield
73.54 (3C, C-50, 2 · benzyl–OCH2) 73.37, 79.69, 79.98,
80.83, 84.87 (5C, C-2, C-3, C-4, C-20, C-30), 99.41 (1C,
C-10), 106.16 (1C, C-1), 110.82 (1C, @CH2), 113.81
(1C, iPrdn), 128.20–138.55 (12C, aryl), 139.85 (1 C, C-
40), 166.63 (1C, C-5).
20
(117 mg, 40%); colourless syrup; ½aꢁ ¼ þ19:0 (c 0.2,
D
CHCl3); C17H22O4 (290.4); 1H NMR (400 MHz,
CDCl3): d 3.34 (s, 3H, OMe), 3.35 (dd, 1H, H-2,
J2,3 = 8.1 Hz), 3.82 (d, 1H, H-5a, J5a,5b = 11.7 Hz),
4.12–4.19 (m, 4H, H-3, H-5b, allyl–OCH2), 4.57 (d,
1H, H-1, J1,2 = 3.6 Hz), 4.61, 4.77 (2 · d, 2 · 1H, ben-
zyl–OCH2), 4.93, 5.11, 5.13, 5.26 ( 4 · m, 4 · 1H,
2 · @CH2), 5.86–5.95 (m, 1H, @CH–), 7.19–7.31 (m,
5H, aryl); 13C NMR (100 MHz, CDCl3): d 54.46 (1C,
OMe), 62.63, 71.58, 72.64 (3C, C-5, allyl–OCH2, ben-
zyl–OCH2), 77.20, 80.23 (2C, C-2, C-3), 98.72 (1C, C-
1), 108.76, 115.72 (2C, 2 · @CH2), 126.70–137.48 (7C,
@CH–, aryl), 141.43 (1C, C-4).
3.16. Methyl 2-O-benzyl-4-deoxy-4-C-methylene-b-L-
threo-pentopyranoside-3-yl-(benzyl 2,3-O-isopropylidene-
a-D-lyxofuranoside)-uronate 18
The synthesis is analogous to compound 12. Employed
are compound 17 (55 mg, 0.22 mmol), (benzyl 2,3-O-
isopropylidene-a-D-lyxofuranoside)-uronate4 (130 mg,
0.44 mmol), anhydrous dichloromethane (40 mL),
DMAP (5 mg, 0.04 mmol) and DCC (108 mg,
0.52 mmol); yield of compound 18 after column
3.14. Methyl 2-O-benzyl-4-deoxy-4-C-methylene-b-L-
threo-pentopyranoside 17
chromatography
(petroleum
ether/ethyl
acetate
20
D
10:1) 106 mg, 91%; colourless syrup; ½aꢁ ¼ þ38:7 (c
1.0, CHCl3); C29H34O9 (526.6); 1H NMR (400 MHz,
The preparation is analogous to that of compound 11.
Employed are compound 16 (112 mg, 0.4 mmol) in
methanol (20 mL), 4-toluenesulfonic acid (60 mg,
0.3 mmol) and palladium/charcoal (10%, 150 mg); col-
CDCl3): d 1.25, 1.42 (2 · s, 2 · 3H, 2 · Me), 3.42 (s,
3H, OMe), 3.60 (dd, 1H, H-20, J2 ,3 = 9.7 Hz), 3.93,
0
0
4.32 (2 · d, 2 · 1 H, H-50a, H-50b, J5 a,5 b = 12.2 Hz),
0
0
4.51, 4.65 (2 · d, 2 · 1H, OCH2), 4.66 (d, 1H, H-10,
umn chromatography (petroleum ether/ethyl acetate
0
0
J1 ,2 = 3.1 Hz), 4.68, 4.74 (2 · d, 2 · 1H, H-2, H-4,
J2,3 = 4.1 Hz), 4.69, 4.87 (2 · d, 2 · 1H, OCH2), 5.01,
5.03 (2 · br s, 2 · 1H, @CH2), 5.09 (dd, 1H, H-3,
J3,4 = 4.1 Hz), 5.29 (s, 1H, H-1, J1,2 = 0 Hz), 5.88 (d,
1H, H-30), 7.26–7.38 (m, 10H, aryl); 13C NMR
(100 MHz, CDCl3): d 25.34, 26.38 (2C, 2 · Me), 55.93
(1C, OMe), 63.67, 69.79, 73.83 (3C, C-50, 2 · benzyl–
OCH2) 74.24, 78.84, 84.80, 81.04, 84.75 (5C, C-2, C-3,
C-4, C-20, C-30), 99.95 (1C, C-10), 106.30 (1C, C-1),
110.67 (1C, @CH2), 113.81 (1C, iPrdn), 128.20–138.78
(12C, aryl), 139.87 (1C, C-40), 166.81 (1C, C-5).
20
5:1); yield (59 mg, 61%) colourless syrup; ½aꢁ
¼
D
þ62:4 (c 0.5, CHCl3); C14H18O4 (250.3); 1H
NMR (400 MHz, CDCl3): d 3.25 (dd, 1H, H-2,
J2,3 = 9.9 Hz), 3.32 (s, 3H, OMe), 3.83 (d, 1H, H-5a,
J5a,5b = 12.7 Hz), 4.17 (d, 1H, H-5b), 4.46 (d, 1H, H-3)
4.62 (s, 2H, benzyl–OCH2) 4.64 (d, 1H, H-1,
J1,2 = 3.4 Hz), 4.94, 5.16 (2 · br s, 2 · 1H, @CH2),
7.24–7.30 (m, 5H, aryl); 13C NMR (100 MHz, CDCl3):
d 54.42 (1C, OMe), 62.29, 71.98 (2C, C-5, benzyl–
OCH2) 68.55, 81.62 (2C, C-2, C-3), 97.41 (1C, C-1),
107.56 (1C, @CH2), 127.07–136.41 (6C, aryl), 141.86
(1C, C-4).
3.17. Methyl [benzyl 2,3-O-isopropylidene-4-C-(methyl 2-
O-benzyl-3,4-dideoxy-a-L-glycero-pent-3-enopyranoside-
4-yl)-methyl a-D-lyxofuranoside]-uronate 13a and methyl
[benzyl 2,3-O-isopropylidene-4-C-(methyl 2-O-benzyl-3,4-
dideoxy-a-L-glycero-pent-3-enopyranoside-4-yl)-methyl
b-L-ribofuranoside]-uronate 13b
3.15. Methyl 2-O-benzyl-4-deoxy-4-C-methylene-b-D-
threo-pentopyranoside-3-yl-(benzyl 2,3-O-isopropylidene-
a-D-lyxofuranoside)-uronate 12
A solution of compound 11 (212 mg, 0.85 mmol) and
(benzyl 2,3-0-isopropylidene-a-D-lyxofuranoside)-uro-
nate4 (375 mg, 1.27 mmol) in anhydrous dichloro-
methane (35 mL) was treated with DMAP (21 mg,
0.17 mmol) and DCC (315 mg, 1.6 mmol) under ice
cooling. With stirring, the mixture was warmed to room
temperature. For work-up the filtrate was concentrated
under reduced pressure and the remainder purified by
column chromatography (petroleum ether/ethyl acetate
A solution of compound 12 (145 mg, 0.275 mmol) in
anhydrous THF (1.5 mL) and HMPA (0.375 mL) was
cooled under argon to ꢀ100 ꢁC and treated with chloro-
trimethylsilane (130 lL, 1.0 mmol). A freshly prepared
and ꢀ78 ꢁC precooled solution of lithium diisopropyl-
amide obtained from diisopropylamine (84 lL,
0.64 mmol) in THF (0.5 mL) and n-butyllithium in hex-
ane (1.6 M, 0.36 mL) was dropwise added such that the
temperature could be maintained at ꢀ100 ꢁC. After
addition, the mixture was warmed to room temperature
within 40 min and kept under stirring for 5 h. A solution
of tetrabutylammonium fluoride in THF (1 M, 1.5 mL)
was then added and stirring continued for 30 min. For
work-up the mixture was diluted with diethyl ether
and extracted with 1 M sodium hydroxide solution.
The alkaline extracts were acidified with concd HCl
and extracted with dichloromethane. After evaporation,
the residue was dissolved in benzene (3 mL) and metha-
nol (1 mL). Then a solution of trimethylsilyldiazome-
thane in hexane (2 M, 0.15 mL) was added and stirred
10:1) to give compound 12 (310 mg, 70%) as a colourless
20
D
syrup; ½aꢁ ¼ ꢀ52:3 (c 1.0, CHCl3); C29H34O9 (526.6);
1H NMR (400 MHz, CDCl3): d 1.30, 1.40 (2 · s,
2 · 3H, 2 · Me), 3.43 (s, 3 H, OMe), 3.55 (dd, 1H, H-
20, J2 ,3 = 10.2 Hz), 3.91, 4.31 (2 · d, 2 · 1H, H-50a, H-
0
0
50b, J5 a,5 b = 12.2 Hz), 4.50 (d, 1H, H-4), 4.54 (d, 1H,
OCH2) 4.65 (s, 2H, OCH2) 4.69 (d, 1H, H-2,
J2,3 = 5.6 Hz), 4.73 (d, 1H, OCH2), 4.77 (d, 1H, H-10,
0
0
0
0
J1 ,2 = 3.9 Hz), 4.97 (br s, 1H, @OCH2) 5.00 (dd, 1H,
H-3, J3,4 = 4.1 Hz), 5.29 (s, 1H, H-1, J1,2 = 0 Hz), 5.31
(br s, 1H, @CH2), 5.86 (d, 1H, H-30), 7.22–7.37 (m,
10H, aryl); 13C NMR (100 MHz, CDCl3): d 25.67,
26.39 (2C, 2 · Me), 55.84 (1C, OMe), 63.76, 69.88,

B. Werschkun, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 569–576
575
for 40 min. The reaction mixture was evaporated to dry-
ness, purified and separated by column chromatography
(petroleum ether/ethyl acetate 10:1).
(2 · s, 2 · 3H, 2 · OMe), 3.80 (d, 1H, H-50a,
J5 a,5 b = 16.1 Hz), 3.94 (br s, 1H, H-20), 4.03 (d, 1H,
0
0
H-50b), 4.45 (d, 2H, OCH2), 4.50 (d, 1H, H-2/H-3),
4.61 (d, 1H, H-10, J1 ,2 = 2.0 Hz), 4.62 (d, 1H, OCH2),
4.71 (d, 1H, H-2/H-3, J2,3 = 6.1 Hz), 4.73 (d, 1H,
OCH2), 5.32 (s, 1H, H-1, J1,2 = 0 Hz), 5.59 (s, 1H, H-
30), 7.17–7.29 (m, 10H, aryl); 13C NMR (100 MHz,
CDCl3): d 23.88, 24.88 (2C, 2 · Me), 39.86 (1C, CH2),
51.43, 54.88 (2C, 2 · OMe), 61.67, 69.46, 69.88 (3C, C-
50, 2 · benzyl–OCH2) 69.95, 84.12, 85.55 (3C, C-2, C-
3, C-20), 90.77 (1C, C-4), 96.25 (1C, C-10), 107.32 (1C,
C-1), 112.38 (1C, iPrdn), 121.12 (1C, C-30), 126.55–
137.45 (13C, C-40, aryl), 169.00 (1C, C-5).
0
0
Compound 13a: 12 mg, 8%; yellowish syrup;
20
D
½aꢁ ¼ ꢀ12:2 (c 1.0, CHCl3); C30H36O9 (540.6); 1H
NMR (400 MHz, CDCl3): d 1.21, 1.34 (2 · s, 2 · 3H,
2 · Me), 2.49, 2.70 (2 · d, 2 · 1H, CH2), 3.35, 3.68
(2 · s, 2 · 3H, 2 · OMe), 3.98 (br s, 1H, H-20), 3.90,
4.10 (2 · d, 2 · 1H, H-50a, H-50b, J5 a,5 b = 16.1 Hz),
4.49 (d, 1H, OCH2), 4.56 (s, 2H, OCH2), 4.61 (s, 1H,
H-10), 4.63, 4.69 (2 · d, 2 · 1H, H-2, H-3,
J2,3 = 5.4 Hz), 4.74 (d, 1H, OCH2), 5.31 (s, 1H, H-1,
J1,2 = 0 Hz), 5.53 (br s, 1H, H-30), 7.14–7.29 (m, 10H,
aryl); 13C NMR (100 MHz, CDCl3): d 23.94, 24.96
(2C, 2 · Me), 40.01 (1C, CH2), 51.24, 54.86 (2C,
2 · OMe), 61.79, 69.69, 70.13 (3C, C-50, 2 · benzyl–
OCH2) 70.16, 84.15, 85.34 (3C, C-2, C-3, C-20), 91.59
(1C, C-4), 95.91 (1C, C-10), 107.68 (1C, C-1), 112.38
(1C, iPrdn), 121.11 (1C, C-30), 126.67–137.38 (13C, C-
40, aryl), 168.57 (1C, C-5).
0
0
Compound 19b: 15 mg, 17% yellowish syrup;
20
D
½aꢁ ¼ þ64:5 (c 1.0, CHCl3); C30H36O9 (540.6); 1H
NMR (400 MHz, CDCl3): d 1.25, 1.39 (2 · s, 2 · 3H,
2 · Me), 2.41, 2.56 (2 · d, 2 · 1H, CH2), 3.42, 3.46
(2 · s, 2 · 3H, 2 · OMe), 2.95 (br s, 1H, H-20), 4.00,
4.16 (2 · d, 2 · 1H, H-50a, H-50b, J5 a,5 b = 16.3 Hz),
4.40 (d, 1H, OCH2), 4.56 (d, 1H, H-2, J2,3 = 5.9 Hz),
0
0
4.57 (s, 2H, OCH2), 4.64 (d, 1H, H-10, J1 ,2 = 3.1 Hz),
4.69 (d, 1H, OCH2), 5.02 (s, 2H, H-1, J1,2 = 0 Hz),
5.16 (d, 1, H-3), 5.44 (s, 1H, H-30), 7.14–7.29 (m, 10H,
aryl); 13C NMR (100 MHz, CDCl3): d 23.79, 24.99
(2C, 2 · Me), 36.64 (1C, CH2), 51.11, 54.82 (2C,
2 · OMe), 61.84, 68.20, 70.08 (3C, C-50, 2 · benzyl–
OCH2) 70.11, 81.21, 83.87 (3C, C-2, C-3, C-20), 88.59
(1C, C-4), 95.94 (1C, C-10), 104.96 (1C, C-1), 111.57
(1C, iPrdn), 121.47 (1C, C-30), 126.63–137.42 (13C, C-
40, aryl), 171.09 (1C, C-5).
0
0
Compound 13b: 11 mg, 7%; yellowish syrup;
20
D
½aꢁ ¼ þ25:7 (c 1.0, CHCl3); C30H36O9 (540.6); H
NMR (400 MHz, CDCl3): d 1.26, 1.39 (2 · s, 2 · 3H,
2 · Me), 2.49, 2.58 (2 · d, 2 · 1H, CH2), 3.42, 3.45
(2 · s, 2 · 3H, 2 · OMe), 3.94 (s, 1H, H-20), 3.96, 4.10
(2 · d, 2 · 1H, H-50a, H-50b, J5 a,5 b = 16.0 Hz), 4.41
0
0
(d, 1H, OCH2), 4.57 (d, 1H, H-10, J1 ,2 = 2.0 Hz), 4.59
(d, 1H, H-2, J2,3 = 5.9 Hz), 4.63, 4.65 (2 · d, 3H,
OCH2), 4.98 (s, 1H, H-1, J1,2 = 0 Hz), 5.19 (d, 1H, H-
3), 5.42 (s, 1H, H-30), 7.19–7.29 (m, 10H, aryl); 13C
NMR (100 MHz, CDCl3): d 23.83, 23.05 (2C, 2 · Me),
35.84 (1C, CH2), 51.15, 54.81 (2C, 2 · OMe), 61.99,
68.17, 70.05 (3C, C-50, 2 · benzyl–OCH2) 70.17, 80.39,
84.24 (3 C, C-2, C-3, C-20), 88.22 (1C, C-4), 96.16 (1C,
C-10), 104.77 (1C, C-1), 111.55 (1C, iPrdn), 121.89
(1C, C-30), 126.64–137.45 (13C, C-40, aryl), 171.14 (1C,
C-5).
0
0
Acknowledgements
Support of this work by the Fonds der Chemischen
Industrie and the Deutsche Forschungsgemeinschaft
(SFB 470) is gratefully acknowledged.
References
3.18. Methyl [benzyl 2,3-O-isopropylidene-4-C-(methyl 2-
O-benzyl-3,4-dideoxy-a-D-glycero-pent-3-enopyranoside-
4-yl)-methyl a-D-lyxofuranoside]-uronate 19a and methyl
[benzyl 2,3-O-isopropylidene-4-C-(methyl 2-O-benzyl-3,4-
dideoxy-a-D-glycero-pent-3-enopyranoside-4-yl)-methyl
b-L-ribofuranoside]-uronate 19b
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The synthesis and work-up is analogous to that for
13a and 13b. Employed are compound 18 (84 mg,
0.16 mmol); (a) THF (1 mL), HMPA (0.25 mL), chloro-
trimethylsilane (90 lL, 0.71 mmol) diisopropylamine
(56 lL, 0.43 mmol), in THF (0.5 mL), n-butyllithium
in hexane (1.6 M, 0.25 mL); (b) tetrabutylammonium-
fluoride in THF (1 M, 1 mL); (c) benzene (3 mL), meth-
anol (1 mL), trimethylsilyldiazomethane in hexane (2 M,
0.1 mL); column chromatography (petroleum ether/
ethyl acetate 5:1).
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S.; Murakami, N.; Kitagawa, I. Tetrahedron 1994, 50,
9961–9974.
Compound 19a: 19 mg, 22% yellowish syrup;
20
½aꢁ ¼ þ18:1 (c 1.0, CHCl3); C30H36O9 (540.6); 1H
D
NMR (400 MHz, CDCl3): d 1.22, 1.34 (2 · s, 2 · 3H,
2 · Me), 2.53, 2.71 (2 · d, 2 · 1H, CH2), 3.39, 3.73

576
B. Werschkun, J. Thiem / Tetrahedron: Asymmetry 16 (2005) 569–576
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