A divergent synthesis of uncommon sugars from furanaldehyde

Article abstract of DOI:10.1055/s-2005-869846

A practical synthetic strategy has been developed for producing uncommon sugars. This method employed kinetic enzymatic resolution of 1-(2-furyl)ethanol, and followed by NBS-mediated Achmatowicz rearrangement to construct α,β-unsaturated lactones. After further derivatization, five representative uncommon sugar units were successfully synthesized. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2005-869846

LETTER
1547
A Divergent Synthesis of Uncommon Sugars from Furanaldehyde
Preparation of
U
i
ncomm
z
on
S
ugarshi Zhu, Arindam Talukdar, Guisheng Zhang, James P. Kedenburg, Peng George Wang*
Department of Biochemistry, The Ohio State University, 484 West 12th Avenue, Columbus, OH 43210, USA
Fax +1(614)6883106; E-mail: wang.892@osu.edu
Received 28 February 2005
based product, is used as starting material for preparation
of the chiral a,b-unsaturated lactones. As an alternative
way to construct the desired a,b-unsaturated lactones, this
strategy is more economic and more practical for large
Abstract: A practical synthetic strategy has been developed for
producing uncommon sugars. This method employed kinetic enzy-
matic resolution of 1-(2-furyl)ethanol, and followed by NBS-medi-
ated Achmatowicz rearrangement to construct a,b-unsaturated
lactones. After further derivatization, five representative uncom- scale manipulations. Finally after further derivatization,
mon sugar units were successfully synthesized.
five different uncommon sugar units were synthesized
starting from one a,b-unsaturated lactone.
Key words: uncommon sugar, enzymatic kinetic resolution, 1-(2-
furyl)ethanol, Achmatowicz rearrangement
Previously, the resolution of furfuryl alcohol has been
well studied using either enzymatic methods or metal-cat-
alyzed kinetic resolution.8 Ghanem et al.8a,b employed cy-
clodextrin (CD) to enhance the reaction rate and
stereoselectivity in lipase-catalyzed transesterification for
kinetic resolution of 1-(2-furyl)ethanol. Mandal et al.8c
utilized Pd-catalyzed oxidation to resolve racemic 1-(2-
furyl)ethanol in excellent stereoselectivity. In 1999,
O’Doherty’s group developed a methodology to prepare
D- and L-sugars through Sharpless asymmetric dihydrox-
ylation to establish the absolute stereochemistry.9 In addi-
tion, Honda,10 Sato11 and Zhou12 have employed
Sharpless asymmetric epoxidation to produce an optically
pure pyranone from racemic 1-(2-furyl)ethanol. The key
intermediate, pyranone, can be transformed into our de-
sired a,b-unsaturated lactones conveniently. Compared
with the previous strategies, our enzymatic resolution is
more convenient for large scale manipulation, and the uti-
lization of NBS instead of Sharpless complex further re-
duced the cost in making optically pure 1-(2-
furyl)ethanol.
Deoxysugars and aminosugars, the so-called uncommon
sugars, are often found in the structure of bioactive drugs.
Here, the function of the deoxysugar moiety ranges from
affecting the pharmacokinetics of the drug to directly in-
teracting with cellular targets like proteins, RNA and
DNA.1 Because of their biologically importance in natural
products, many efforts have been put on the total synthesis
of uncommon monosaccharides.2 Traditionally, the syn-
theses of optically active uncommon sugars have been ini-
tiated from carbohydrate based materials. For instance, L-
vancosamine was synthesized from methyl glucoside in
fifteen steps.3 The major disadvantage of this approach is
the long reaction sequence required for protection and
deprotection manipulations. The total synthesis of uncom-
mon sugars from non-carbohydrate precursors remains
one of the challenging problems in organic synthesis.4 For
example, O’Doherty’s group synthesized sugar deriva-
tives starting from furan alcohols.5 MacMillan’s group
has developed a synthetic pathway for stereoselectively
constructing sugar derivatives starting from b,g-oxyalal-
dehydes.6 Recently, our group developed a novel strategy
for generating six-membered b,g-unsaturated lactones us-
ing ring-closing metathesis (RCM),7 which could be con-
veniently converted to uncommon sugar derivatives. This
method provided a synthetic pathway to produce uncom-
mon sugars systematically. In our research, we plan to
construct an uncommon sugar library to facilitate the sys-
tematic structure–activity-relationship (SAR) investiga-
tion of the potential anticancer drugs. Therefore, it is
necessary to develop a more efficient and practical syn-
thetic pathway to deliver uncommon sugars.
O
O
O
OH
O
X
R
OH
Y
2,6-deoxysugars
α,β-unsaturated lactone
X = OH, H; Y = H, OH
(R)-1-(2-furyl)
ethanol (1)
Scheme 1
We began our synthetic strategy with the methylation of
the furanaldehyde (Scheme 2) by using MeMgCl reacted
with furanaldehyde in THF at 0 °C. The racemic alcohol
obtained was readily subjected to the kinetic enzymatic
resolution condition in the presence of isopropenyl acetate
as an acetyl group donor. In order to find optimized ste-
reochemistry output, different lipases were scanned. The
results were summarized in Table 1. The reaction was
monitored by GC (Agilent 6850 system equipped with
Cyclodex-BTM chiral capillary column, 0.25 mm × 30 m)
analysis. Six different commercially available lipases
were tested. It was found that the esterification of the
alcohol under lipase PS (from Pseudomonas capacia,
Herein, we would like to present our strategy (Scheme 1)
to achieve the deoxysugars by employing enzymatic reso-
lution of 1-(2-furyl)ethanol followed by Achmatowicz re-
arrangement. In this pathway, furanaldehyde, an agro-
SYNLETT 2005, No. 10, pp 1547–1550
1
7
.0
6
.2
0
0
5
Advanced online publication: 12.05.2005
DOI: 10.1055/s-2005-869846; Art ID: S02605ST
© Georg Thieme Verlag Stuttgart · New York

1548
L. Zhu et al.
LETTER
immobilized on ceramic particles, entry 1 in Table 1) is 1-(2-furyl)-ethanol acetate to produce the optically pure
not very efficient. After 10 hours stirring with the enzyme, alcohol. However, it worked perfectly for us to use this
45% of the starting alcohol was converted to the ester. In enzyme for deprotection of the acetate 2 to produce the
addition, it was found that the alcohol (S)-1 and com- (R)-1 (Scheme 2).19 Thus, both (R)-1 and (S)-1 were ob-
pound 2 was obtained in 70% and 89% ee, respectively. tained in their optically pure form. Employing this enzy-
Lipase from Candida antarctica (entry 2 in Table 1) cata- matic resolution in one batch we were able to generate
lyzed the esterification very fast. After 1.5 hours, 45% of >20 g of optically pure 1-(2-furyl)-ethanol for further syn-
the alcohol was converted to the corresponding acetate, thetic manipulations.
and after 2 hours, 49% conversion rate was reached. Un-
fortunately, the optical purities of the alcohol and the ester
are not satisfied (entry 2 in Table 1). Acetate 2 was ob-
The transformation of the (R)-1 to the corresponding a,b-
unsaturated lactone 5 and 6 was outlined in Scheme 2.
Transformation of these 1-(2-furyl)ethanols to pyranone
tained in 90% ee at 44% conversion rate. Amamo Lipase
was performed in presence of NBS in THF–H2O media
from Burkholderia cepacia (entry 3 in Table 1) catalyzed
(Scheme 2). Column chromatography provided com-
pound 3 in 93% yield. Preceding literature reported that
the esterification very slow, only 11% conversion was
achieved after 12 hours. On the other hand, lipase from
Rhizopus oryzea and porcine pancrease does not show any
conversion even after 2 days of reaction (entry 4 and 5 in
Table 1). The best results were obtained by utilizing No-
vozyme 435 (immobilized on acrylic resin, entry 6 in
the unsaturated ketone could be oxidized with Jones re-
agent, or MnO2.13 However, we found that these two re-
agents did not work well (<30% yield) for the
transformation of compound 3 to compound 4. On scruti-
nizing various oxidation conditions, finally we were con-
Table 1). When the reaction was stopped at 45% conver-
tended with result obtained by CrO3·NH4Cl complex.14
sion rate (2.5 h), the ester 2 was obtained in >97% ee. On
Compound 415 was instantly subjected to Luche
the other hand, when the reaction was stopped at 55%
reduction16 with NaBH4 in the presence of CeCl3. The un-
conversion rate (4.0 h), the 1-(2-furyl)ethanol, (S)-1, was
saturated ketone was successfully reduced to produce de-
sired a,b-unsaturated lactone 5 and 6 in 75% yield from
compound 3. Interestingly, it was observed that when the
obtained in >95% ee. In addition, it was found that the hy-
drolysis of the corresponding acetate by Novozyme 435
(ordered from Aldrich and used directly) is extremely fast,
which make this enzyme not suitable for hydrolyzing the
tion leads to product with different stereoselectivity.
reaction was performed at different temperature, the reac-
Table 1 Kinetic Enzymatic Resolution of the 1-(2-Furyl)ethanol
Entry
Lipase
Reaction time (h)a Conversion rateb
ee (%) of (S)-1b
ee (%) of 2b
1
2
Lipase PS (immobilized)
Lipase from Candida antatica
10
45%
70
89
1.5
2.0
44%
49%
85
89
90
87
3
4
5
6
Amamo lipase from Burkholderia cepacia
Amamo lipase from Rhizopus oryzea
Lipase from porcine pancrease
12
48
48
11%
90
No reaction
No reaction
Novozyme 435 (immobilized on acrylic resin) 2.5
4.0
45%
55%
70
>97c
60–70
>95c
a Reactions were performed at 40 °C in isopropyl ether.
b Determined by chiral GC analysis.
c Results obtained after column chromatography.
MeMgCl
Lipase
Lipase
+
H
O
O
O
O
PBS buffer, pH = 7.0, r.t.
90%
THF, 0 °C
92%
isopropenyl acetate
diisopropyl ether
O
OH
OH
OAc
(S)-1
1
2
O
OH
O
O
O
O
O
O
CrO3·NH4Cl
NaBH4
NBS, NaHCO3
+
O
CH2Cl2
NaOAc, THF/H2O
93%
CeCl3·7H2O
75% from 3
O
O
HO
HO
OH
(R)-1
3
4
5
6
at 0 °C: 5:6 = 2 :1
–78 °C: only 5 was isolated
Scheme 2
Synlett 2005, No. 10, 1547–1550 © Thieme Stuttgart · New York

LETTER
Preparation of Uncommon Sugars
1549
When the reaction was executed at 0 °C, a separable mix- pyridine, trans-epoxide 13 was obtained exclusively.20
ture of lactone 5 and 6 was obtained in 2:1 ratio. On the Reductive opening of epoxide ring in 13 with sodium phe-
other hand at –78 °C, only lactone 5 was observed.
nylseleno(triisopropyloxy)-borate allowed the formation
of 3,4-trans-dihydroxyl lactone. Removal of the silyl pro-
tecting group with TBAF was clean and high yielding.
Completion of the synthesis required DIBAL-H reduction
of the lactone to give D-canarose (14) in very good yield.
Similarly, starting from (S)-1, corresponding a,b-unsatur-
ated lactones were synthesized by following the same syn-
thetic route. Having successfully achieved an elegant
synthesis of the four key a,b-unsaturated lactones, we
turned our attention to the transformation of these lactones Meanwhile, the stereoselective approach to 3-azido-2,3,6-
to synthesize both D- and L-uncommon sugars. As out- trideoxy sugar was achieved by taking advantage of Mit-
lined in Scheme 3, starting from unsaturated lactone 6, sunobu reaction,17 as depicted in Scheme 3. Following the
five types of D-2,6-dideoxysugars were successfully same procedure for preparation of the D-canarose (14),
synthesized.
precursor 15 was obtained. It was then treated with diphe-
nylphosphoryl azide (DPPA) in presence of DEAD and
triphenylphosphine to give the azido-compound 16 in
80% yield. As a result, the azido-group was introduced in-
versely to afford the deoxy azido sugar with 3,4-cis-di-
functionalities (3,4-cis:3,4-trans > 97:3 by NMR).
Finally, compound 16 was readily converted into the 3-
azido-2,3,6-trideoxy sugar 17 after subsequent treatment
with TBAF and DIBAL-H.20
Hydrogenation of lactone 6 in presence of Pd/C under H2
atmosphere (25 psi), provided saturated g-hydroxy lac-
tone 7. Subsequent reduction with DIBAL-H afforded D-
amicetose (8) in excellent yields. Conversion of D-amice-
tose (8) to azido sugar 9 was done by Mitsunobu
reaction17 (due to the volatile property of the azido com-
pound, compound 920 was obtained as the isopropyl gly-
coside). When lactone 6 was subjected to the epoxidation
conditions (NaClO/pyridine), epoxide 10 was isolated in In summary, by utilizing the enzymatic resolution path-
moderate yield.20 Fortunately, these conditions enabled us way, we were able to generate the a,b-unsaturated lac-
to produce the epoxide compound 10 stereoselectively tones in large scale. The efficiency of our diversity-
with the ratio of cis:trans greater than 20:1. Compound 10 oriented synthesis was exemplified by the successful syn-
was then subjected to selective ring-opening reaction with thesis of five different types of uncommon sugars starting
sodium phenylseleno(triisopropyloxy)borate (NaBH4 and from one a,b-unsaturated lactone. We strategically incor-
PhSeSePh in acetic acid).18 Finally, the reduction of lac- porated azido group in our deoxy sugars, since azido
tone with DIBAL-H, D-digitoxose (11) was obtained in group can be an excellent masking group for amino func-
65% yield (overall yield of two reduction steps).
tionalities and can be amplified to diversify drug-resem-
bling moieties. Additional syntheses of uncommon sugars
are currently undergoing.
In order to synthesize sugars with 3,4-trans-difunctional-
ities, we sought an alternative strategy. As shown in
Scheme 3, silylation of lactone 6 with tert-butyldimethyl-
silyl group gave compound 12. We were pleased to find
that the bulky tert-butyldimethylsilyl group helped to
force the subsequent epoxidation to happen at the anti-
face of the existing hydroxyl group due to steric crowding.
As a result, when compound 12 was treated with NaClO/
Acknowledgment
This work was supported by NSF (CH-0316806) and a fund from
Michigan Life Science Corridor Fund (1632) to P. G. Wang. The
author thanks the Ohio State University for providing research re-
sources, analysis instruments and funding support.
N3
O
O
O
O
1. iPrOH, H+
H2, Pd/C
96%
DIBALH, CH2Cl2
O
HO
O
OH
OH
94%
2. DPPA, PPh3
DEAD
HO
HO
8
7
OPri
9
1. NaBH4, (PhSe)2
AcOH, iPrOH
75%
O
NaClO, pyridine
40%
HO
2. DIBALH
65%
11
O
O
O
OH
O
10
1. NaBH4, (PhSe)2
AcOH, iPrOH
O
O
O
HO
NaClO, pyridine
45%
TBSCl, imidazole
98%
O
O
HO
HO
6
OH
OH
2. TBAF
3. DIBALH
TBSO
TBSO
TBSO
TBSO
14
12
O
13
85%
1. TBSCl, imidazole
2. NaClO, pyridine
O
O
O
O
DPPA, PPh3
1. TBAF
HO
DEAD
80%
2. DIBALH
88%
3. NaBH4, (PhSe)2
AcOH, iPrOH
38% (3 steps)
17
N3
15
OH
16
N3
Scheme 3
Synlett 2005, No. 10, 1547–1550 © Thieme Stuttgart · New York

1550
L. Zhu et al.
LETTER
collected by filtration. Finally, the product was dried under
vacuum to give red-orange flake crystals (21 g). The
oxidation was performed in CH2Cl2 at r.t. in the presence of
CrO3·NH4Cl complex (3–4 equiv).
References
(1) (a) Weymouth-Wilson, A. C. Nat. Prod. Rep. 1997, 14, 99.
(b) Montreuil, J.; Vleigenthart, J. F. G. Glycoproteins;
Elsevier: Amsterdam, 1995. (c) Wiegandt, H. E.
Glycolipids; Elsevier: Amsterdam, 1985. (d) Varki, A.
Glycobiology 1993, 3, 97. (e) Nagarajan, R. Glycopeptide
Antibiotics; Dekker: New York, 1994. (f) Allen, H. J.
Glycoconjugates: Composition, Structure, and Function;
Dekker: New York, 1992.
(15) Compound 4 is not very stable, after reaction it should be
used directly. Storage at 4 °C for 3 d led to decomposition to
a black oil.
(16) Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226.
(17) Dermatakis, A.; Luk, K.-C.; DePinto, W. Bioorg. Med.
Chem. 2003, 11, 1873.
(2) (a) Kirschning, A.; Jesberger, M.; Schoning, K.-U. Synthesis
2001, 507. (b) Marzabadi, C. H.; Franck, R. W. Tetrahedron
2000, 56, 8385. (c) Toshima, K.; Tatsuta, K. Chem. Rev.
1993, 93, 1503. (d) Sztaricskai, F.; Pelyvas-Ferenczik, I.
Glycopeptide Antibiotics; Dekker: New York, 1994.
(e) Hauser, F. M.; Ellenberger, S. R. Chem. Rev. 1986, 86,
35. (f) Hudlicky, T.; Entwistle, D. A.; Pitzer, K. K.; Thorpe,
A. J. Chem. Rev. 1996, 96, 1195.
(3) Pelyvas-Ferenczik, I.; Monneret, C.; Herczegh, P. Synthetic
Aspects of Aminodeoxy Sugars of Antibiotics; Springer-
Verlag: Berlin, 1988.
(4) (a) For a comprehensive review based on stereoselective
syntheses of carbohydrates, see: McGarvey, G. J.; Kimura,
M.; Oh, T.; Williams, J. M. J. Carbohydr. Chem. 1984, 3,
125; and references cited therein. (b) Behrens, C. H.;
Sharpless, K. B. Aldrichimica Acta 1983, 16, 67; and
references cited therein.
(5) (a) Babu, R. S.; Zhou, M.; O’Doherty, G. A. J. Am. Chem.
Soc. 2004, 126, 3428. (b) Haukaas, M. H.; O’Doherty, G. A.
Org. Lett. 2002, 4, 1771.
(6) (a) Northrup, A. B.; Mangion, I. K.; Hettche, F.; MacMillan,
D. W. C. Angew. Chem. Int. Ed. 2004, 43, 2152.
(b) Northrup, A. B.; MacMillan, D. W. C. Science 2004, 305,
1752.
(18) (a) Takano, S.; Shimazaki, Y.; Sekiguchi, Y.; Ogasawara, K.
Synthesis 1989, 539. (b) Miyashita, M.; Suzuki, T.;
Yoshikoshi, A. Tetrahedron Lett. 1987, 28, 4293.
(19) Procedure for Kinetic Enzymatic Resolution of (R)-1-(2-
Furyl)ethanol.
To a stirred mixture of 1-(2-furyl)ethanol (60 g, 0.54 mol)
and isopropenyl acetate (200 mL, 1.82 mol) in diisopropyl
ether (200 mL) was added Novozyme 435 (3.0 g). The
reaction mixture was warmed to 40 °C and monitored by GC
analysis. The reaction was stopped by filtration when 45%
conversion rate was reached (ca. 2.5 h). The filtrate was
concentrated on rotary evaporator. The residue was
subjected for fractional distillation and collected the fraction
at 82–85 °C/25 mmHg. The yellow oil obtained was
consequently mixed with PBS buffer (pH = 7.0, 1.2 L) and
Novozyme 435 (2.0 g) and stirred at r.t. for 2 h. TLC
indicated the completion of the hydrolysis. The enzyme was
removed by filtration and the aqueous solution was extracted
with EtOAc (6 × 150 mL). The combined organic phases
were dried over MgSO4 and concentrated under vacuum.
The crude product was purified by column chromatography
(hexanes–EtOAc, 10:1) to give (R)-1 (21.5 g, >97% ee by
chiral GC analysis).
(20) Spectroscopic data.
(7) (a) Andreana, P. R.; McLellan, J. S.; Chen, Y.; Wang, P. G.
Org. Lett. 2002, 4, 3875. (b) Zhu, L.; Kedenburg, J. P.;
Xian, M.; Wang, P. G. Tetrahedron Lett. 2005, 46, 811.
(8) (a) Ghanem, A. Org. Biomol. Chem. 2003, 1, 1282.
(b) Ghanem, A.; Schurig, V. Tetrahedron: Asymmetry 2003,
14, 2547. (c) Mandal, S. K.; Sigman, M. S. J. Org. Chem.
2003, 68, 7535. (d) Akai, S.; Naka, T.; Omura, S.;
Tanimoto, K.; Imanishi, M.; Takebe, Y.; Matsugi, M.; Kita,
Y. Chem.–Eur. J. 2002, 8, 4255.
Compound 9 was obtained as its a-anomer from the coupling
constant of the anomeric proton signal. The parent ion was
not observed by HRMS, due to decomposition of this
compound under the analysis conditions. IR (neat): 2950,
2100 (N3 group), 1275, 1050 cm–1. 1H NMR (250 MHz,
CDCl3): d = 4.96 (d, J = 3.0 Hz, 1 H), 4.09 (qd, J = 6.5, 1.8
Hz, 1 H), 3.91 (sept, J = 6.1 Hz, 1 H), 3.48 (m, 1 H), 2.14 (m,
1 H), 1.95 (m, 2 H), 1.56 (m, 1 H), 1.22 (d, J = 6.5 Hz, 6 H),
1.16 (d, J = 6.1 Hz, 3 H). 13C NMR (63 MHz, CDCl3): d =
94.2, 67.9, 64.8, 59.8, 24.3, 23.0, 22.7, 21.2, 17.6.
Compound 10: 1H NMR (400 MHz, CD3OD): d = 4.37–4.32
(m, 1 H), 3.86 (d, J = 9.0 Hz, 1 H), 3.67 (d, J = 4.2 Hz, 1 H),
3.62 (d, J = 4.2 Hz, 1 H), 1.34 (d, J = 6.3 Hz, 3 H). 13C NMR
(100 MHz, CD3OD): d = 167.6, 73.4, 71.1, 55.9, 50.5, 17.1.
HRMS (ESI): m/z calcd for C6H8O4Na: 167.0320 [M + Na+].
Found: 167.0324.
(9) Harris, J. M.; Keranen, M. D.; O’Doherty, G. A. J. Org.
Chem. 1999, 64, 2982.
(10) (a) Kametani, T.; Tsubuki, M.; Tatsuzaki, Y.; Honda, T.
Heterocycles 1988, 27, 2107. (b) Kametani, T.; Tsubuki,
M.; Tatsuzaki, Y.; Honda, T. J. Chem. Soc., Perkin Trans. 1
1990, 639. (c) Honda, T.; Kametani, T.; Kanai, K.;
Tatsuzaki, Y.; Tsubuki, M. J. Chem. Soc., Perkin Trans. 1
1990, 1733.
(11) (a) Kobayashi, Y.; Kusakabe, M.; Kitano, Y.; Sato, F. J.
Org. Chem. 1988, 53, 1587. (b) Kusakabe, M.; Kitano, Y.;
Kobayashi, Y.; Sato, F. J. Org. Chem. 1989, 54, 2085.
(12) (a) Yang, Z.-C.; Zhou, W.-S. Tetrahedron Lett. 1995, 36,
5617. (b) Yang, Z.-C.; Jiang, X.-B.; Wang, Z.-M.; Zhou, W.-
S. J. Chem. Soc., Chem. Commun. 1995, 2389.
(13) Harris, J. M.; Keranen, M. D.; Nguyen, H.; Young, V. G.;
O’Doherty, G. A. Carbohydr. Res. 2000, 328, 17.
(14) (a) Zhang, G.; Wang, J.; Cheng, M.; Cai, K. Chin. Chem.
Lett. 1994, 5, 105. (b) The CrO3·NH4Cl complex was
synthesized according to the paper: CrO3 (20 g) was
dissolved in a minimum amount of H2O (ca. 10–12 mL).
Then NH4Cl (8.6 g, 1 equiv) was added in portions as solid.
The mixture was allowed to stir at r.t. for 10 min and then
warm up to 40 °C to ensure a homogenous solution was
obtained. After being cooled down to r.t., the crystals were
Compound 13: 1H NMR (400 MHz, CD3OD): d = 4.48–4.42
(m, 1 H), 3.92 (d, J = 9.2 Hz, 1 H), 3.63 (d, J = 4.4 Hz, 1 H),
3.54 (d, J = 4.4 Hz, 1 H), 1.33 (d, J = 6.4 Hz, 3 H), 0.93 (s,
9 H), 0.18 (s, 3 H), 0.15 (s, 3 H).
13C NMR (100 MHz, CD3OD): d = 166.7, 73.3, 71.0, 55.9,
50.7, 25.8, 18.3, –3.9, –4.5. HRMS (ESI): m/z calcd for
C12H22O4SiNa: 281.1185 [M + Na+]. Found: 281.1190.
Compound 17 was obtained as a mixture of a/b-anomers,
selected data for b-anomer: 1H NMR (400 MHz, CD3OD):
d = 5.03 (dd, J = 9.0, 2.3 Hz, 1 H), 4.10 (q, J = 3.5 Hz, 1 H),
3.64 (dq, J = 9.2, 6.3 Hz, 1 H), 3.41 (m, 1 H), 2.14 (q,
J = 14.0 Hz, 1 H), 1.83 (m, 1 H), 1.32 (d, J = 6.7 Hz, 3 H).
13C NMR (100 MHz, CD3OD): d = 90.8, 69.7, 67.0, 63.1,
32.1, 15.3. [a]D25 38 (c 1.0, MeOH-d4). HRMS (EI): m/z
calcd for C6H11N3O3: 173.0796. Found: 173.0802.
Synlett 2005, No. 10, 1547–1550 © Thieme Stuttgart · New York