Synthesis of novel caged intramolecular ketals of β-C-glycopyranosidic ketones

Article abstract of DOI:10.1080/07328300701609111

Novel caged intramolecular ketals of β-C-glycosidic ketones were prepared from pyranoses. The structures of the new compounds were elucidated by NMR and HRMS spectral analysis. Preliminary studies revealed that the intramolecular ketal could be used to pr

Full text of DOI:10.1080/07328300701609111

This article was downloaded by: [University of California Santa Cruz]
On: 02 December 2014, At: 16:00
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office:
Mortimer House, 37-41 Mortimer Street, London W1T 3JH, UK
Journal of Carbohydrate Chemistry
Publication details, including instructions for authors and subscription
information:
http://www.tandfonline.com/loi/lcar20
Synthesis of Novel Caged Intramolecular
Ketals of β‐C‐Glycopyranosidic Ketones
Lin Yan a , Feng‐Wu Liu a , Jian‐Li Yang a & Hong‐Min Liu a
a New Drug Research & Development Center, Zhengzhou University ,
Zhengzhou, P. R. China
Published online: 31 Aug 2007.
To cite this article: Lin Yan , Feng‐Wu Liu , Jian‐Li Yang & Hong‐Min Liu (2007) Synthesis of Novel Caged
Intramolecular Ketals of β‐C‐Glycopyranosidic Ketones, Journal of Carbohydrate Chemistry, 26:5-6, 339-347,
DOI: 10.1080/07328300701609111
To link to this article: http://dx.doi.org/10.1080/07328300701609111
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”)
contained in the publications on our platform. However, Taylor & Francis, our agents, and our
licensors make no representations or warranties whatsoever as to the accuracy, completeness, or
suitability for any purpose of the Content. Any opinions and views expressed in this publication
are the opinions and views of the authors, and are not the views of or endorsed by Taylor &
Francis. The accuracy of the Content should not be relied upon and should be independently
verified with primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities
whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or
arising out of the use of the Content.
This article may be used for research, teaching, and private study purposes. Any substantial
or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or
distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use
can be found at http://www.tandfonline.com/page/terms-and-conditions

Journal of Carbohydrate Chemistry, 26:339–347, 2007
Copyright # Taylor & Francis Group, LLC
ISSN: 0732-8303 print 1532-2327 online
DOI: 10.1080/07328300701609111
Synthesis of Novel Caged
Intramolecular Ketals of
b-C-Glycopyranosidic
Ketones
Lin Yan, Feng-Wu Liu, Jian-Li Yang, and Hong-Min Liu
New Drug Research & Development Center, Zhengzhou University, Zhengzhou,
P. R. China
Novel caged intramolecular ketals of b-C-glycosidic ketones were prepared from pyra-
noses. The structures of the new compounds were elucidated by NMR and HRMS
spectral analysis. Preliminary studies revealed that the intramolecular ketal could be
used to protect 3- and 6-hydroxyl groups of b-C-glycosidic ketones.
Keywords Caged molecule, b-C-Glycosidic ketone, Intramolecular ketal, Protecting
group
INTRODUCTION
The ketal group is one of the most widely used carbohydrate protecting
groups[1,2] commonly employed for the protection of vicinal hydroxyl groups.
However, there is no case of protecting 3- and 6-hydroxyl groups on a sugar
molecule by a ketal group as reported herein for the preparation of novel
caged intramolecular ketals from b-C-glycosidic ketones through an intramole-
cular ketal reaction. The utility of these new caged compounds is similar to
those of myo-inositol orthoesters, which are a class of important intermediates
for the synthesis of phosphoinositols[3] and other molecules with interesting
properties.[4] Gathering a number of specific properties such as caged struc-
ture, chirality, rigidity, and relative stability in one polycyclic system, these
new C-glycoside derivatives may be useful intermediates for synthesis of a
variety of 2- and 4-substituted pyranose derivatives.
Address correspondence to Hong-Min Liu, New Drug Research & Development Center,
Zhengzhou University, Zhengzhou 450052, P. R. China. E-mail: liuhm@zzu.edu.cn
339

L. Yan et al.
The development of synthetic methodology for C-glycosides is largely
340
stimulated by their occurrence as building blocks in a variety of biologically
important natural products[5] and by the fact that they may serve as promising
biological tools and potential therapeutics.[6] A number of recent reviews have
been devoted to this subject.[7] Control of anomeric stereochemistry in the
course of glycosylation is a key consideration in the synthesis of C-glycoside.
Recently, Lubineau and coworkers reported a convenient, one-pot synthesis
of b-C-glycosidic ketones in aqueous media.[8] Following this attractive
method, we attempted to convert other free sugars to b-C-glycoside and
further to prepare more elaborate C-glycoside derivatives.
RESULTS AND DISCUSSION
In our previous papers, we reported the preparation of 10,40:30,60-dianhydro-4-
chloro-4-deoxy-galacto-sucrose by using sucralose as the starting material[9]
and further hydrolysis to afford 4-chloro-4-deoxy-a-D-galactopyranose (1).[10]
Condensation of the new unnatural sugar 1 with pentane-2,4-dione in
aqueous alkaline solution by following the procedures in the literature[8]
gave 1-(4-chloro-4-deoxy-b-D-galactopyranosyl)-propan-2-one (2) in an almost
quantitative yield (Sch. 1). The structure of ketone 2 was confirmed by
spectral analysis. The large coupling constants between H-1 and H-2 (J1,2
9.3 Hz) revealed a b-configuration.
¼
When compound 2 was treated with sulfuric acid in refluxing THF for
several hours, a small amount of intramolecular ketal 3 was obtained and
more than half the amount of 2 was left unchanged. The product 3 was sep-
arated from 2 by column chromatography on silica gel. The disappearance
of the signal of the carbonyl group at d 212.5 and the appearance of a
signal at d 99.8 in the 13C NMR spectrum of 3 indicated the formation of a
new ketal carbon. At the same time, the 1H signal of the methyl group
shifted from d 2.19 in 2 to d 1.53 in 3. Two-dimensional NMR analysis
(COSY, HSQC, and HMBC) confirmed the structure showing correlations of
H-10 (d 4.01), H-30 (d 4.13), and H-60 (d 4.07, 4.27) to C-2 (d 99.8) (Fig. 1). Acety-
lation of 3 with acetic anhydride in pyridine generated product 4. Both 1H and
13C NMR spectral data indicated that 4 had only one acetyl group.
Scheme 1

Novel Caged Intramolecular Ketals
341
Figure 1: HMBC correlations for compound 3.
As the preliminary yield of the ketal was disappointing, we attempted
optimization of the reaction conditions. Pleasantly, we found that employment
of acetonitrile as a solvent and phosphoryl trichloride as an acid catalyst in the
reaction not only afforded the product in reasonable yield (82%), but also made
purification easier.
When glucose (5) and galactose (6) were used as starting materials, the cor-
responding b-C-glycosidic ketones 7 and 8 were generated. Subsequent treat-
ment of the ketones with acid afforded intramolecular ketal compounds 9
and 10 (Sch. 2).
The formation of intramolecular ketals caused conversion of the confor-
mation of the pyranose rings from 4C1 to 1C4 in the structure and upfield
shifts of 13C signals to different degrees for most of the carbons compared to
that of the corresponding b-C-glycosidic ketones. In all conversions C-60
signals shifted downfield by 3.6 to 8.3 ppm.
The newly formed compounds consist of four rings including two seven-
membered and two six-membered rings, which gives a rigid and stable caged
structure and forms a cavity in the molecule. The newly formed stereogenic
center (C-2) has a fixed S-configuration. To the best of our knowledge, this
novel structure has never been reported so far.
We performed the conversion of 40-chloro-40-deoxy-b-D-galactopyranosyl-
propan-2-one-30,60-ketal (3) to the corresponding O-tosyl derivative 11, an
important precursor to introduce various substituents. Treatment of ketal 11
with aqueous trifluoroacetic acid at rt overnight furnished C-glycosidic
ketone derivative 12 in 94% (Sch. 3).
Scheme 2

L. Yan et al.
342
Scheme 3
In summary, we have found that b-C-glycosidic ketones readily prepared
from reducing sugars undergo acid-catalyzed intramolecular ketal formation
leading to new caged ketal derivatives. Based on the intramolecular ketal
reactions, a new method for protection of nonvicinal hydroxyls of sugar was
developed, which broadened the methodology for derivation of carbohydrate
compounds. The application of these caged compounds to synthesize a
variety of 2- and 4-substituted carbohydrate analogs is under way.
EXPERIMENTAL
General Methods
The 1H and 13C NMR spectra were recorded on a Bruker AVANCE DPX-400
spectrometer with tetramethylsilane as internal standard and using D2O or
CDCl3 as solvent. Chemical shifts (d) were expressed in ppm downfield from
internal TMS. IR spectra were recorded on a Nicolet IR 200 spectrophotometer.
Elemental analyses were carried out on a MOD 1106 analyzer. HRMS (high-
resolution mass spectra) were taken with a Q-Tof Micromass spectrometer.
Thin-layer chromatography (TLC) was performed on glass plates precoated
with silica gel (5 to 40 mm) to monitor the reactions and certify the purity of
the reaction products. Visualization was accomplished by spraying the
chromatograms with 10% ethanolic sulfuric acid and charring them on a hot
plate. Column chromatography was carried out on silica gel (200 to 300 mesh).
1-(4-Chloro-4-deoxy-b-D-galactopyranosyl)
-propan-2-one (2)
To a solution of 4-chloro-4-deoxy-a-D-galactose (1, 198 mg, 1 mmol) in
water (4 mL) were added sodium bicarbonate (126 mg, 1.5 mmol) and
pentane-2,4-dione (120 mg, 1.2 mmol). After stirring at 908C for about 8 h,
followed by concentration to dryness under diminished pressure and fraction-
ation by chromatography with 8:1 CHCl3-MeOH, 2 was afforded as a syrup
1
(223 mg, 94%): IR (KBr): 3393, 2912, 1708, 1362, 1084 cm21; H NMR (D2O,
400 MHz): d 4.41 (dd, 1H, J4,5 ¼ 0.6 Hz, J4,3 ¼ 3.8 Hz, H-4), 3.86 (m, 1H,
0
0
H-5), 3.84 (m, 1H, H-3), 3.73 (dt, 1H, J1,1 a ¼ 3.1 Hz, J1,1 b, J1,2 ¼ 9.3 Hz,

Novel Caged Intramolecular Ketals
H-1), 3.66 (dd, 1H, J6a,5 ¼ 7.0 Hz, J6a,6b ¼ 11.7 Hz, H-6a), 3.59 (dd, 1H, J6b,5
343
¼
5.4 Hz, J6b,6a ¼ 11.7 Hz, H-6b), 3.49 (t, 1H, J ¼ 9.3 Hz, H-2), 2.96 (dd, 1H,
J1 a,1 ¼ 3.1 Hz, J1 a,1 b ¼ 16.8 Hz, H-10a), 2.70 (dd, 1H, J1 b,1 ¼ 9.3 Hz, J1 b,1 a
¼
0
0
0
0
0
0
13
16.8 Hz, H-10b), 2.19 (s, 3H, H-30); C NMR (D2O, 100 MHz): d 212.5 (C-20),
77.3 (C-5), 76.1 (C-1), 72.5 (C-3), 69.7 (C-2), 62.3 (C-4), 61.0 (C-6), 45.2 (C-10),
29.6 (C-30); HRMS (ESI): Calcd. for C9H15ClO5: 238.0608. Found: 261.0506
[M þ Na]þ. Anal. Calcd. for C9H15ClO5: C, 45.29; H, 6.33. Found: C, 45.31; H, 6.36.
40-Chloro-40-deoxy-b-D-galactopyranosyl-propan-2-one-
30,60-ketal (3)
To a solution of 1-(4-chloro-4-deoxy-b-D-galactosyl)-propan-2-one (2,
238 mg, 1 mmol) in dry acetonitrile (10 mL) was added a catalytic amount of
phosphoryl trichloride. The mixture was stirred at 608C while the progress of
the reaction was monitored by TLC with 12:1 CHCl3-MeOH; after about 6 h,
the starting material was no longer detectable, and the acid present was
then removed by stirring for 30 min with anhydrous sodium carbonate. The
solution was filtered and concentrated. The residue was dissolved in EtOAc,
and the solution was washed with satd aq NaHCO3 (5 mL ꢀ 2) and water
(5 mL ꢀ 3), dried over anhydrous Na2SO4, and concentrated, affording 3
(180 mg, 82%) as an oil: IR (KBr): 3504, 2938, 1184, 1057 cm21 1H NMR
;
(CDCl3, 400 MHz): d 4.75 (dd, 1H, J4 ,5 ¼ 2.8 Hz, J4 ,3 ¼ 6.8 Hz, H-40),
0
0
0
0
4.33 (m, 1H, H-50), 4.27 (dd, 1H, J6a ,5 ¼ 4.4 Hz, J6a ,6b ¼ 13.6 Hz, H-60a),
0
0
0
0
4.13 (m, 1H, H-30), 4.07 (d, 1H, J6b ,6a ¼ 13.6 Hz, H-60b), 4.01 (m, 1H, H-10),
0
0
3.92 (m, 1H, H-20), 2.43 (dd, 1H, J1a,1 ¼ 3.2 Hz, J1a,1b ¼ 15.6 Hz, H-1a), 2.19
0
(dd, 1H, J1b,1 ¼ 3.2 Hz, J1b,1a ¼ 15.6 Hz, H-1b), 1.53 (s, 3H, H-3); 13C NMR
0
(CDCl3, 100 MHz): d 99.8 (C-2), 76.1 (C-50), 72.3 (C-30), 69.2 (C-60), 68.7 (C-10),
68.4 (C-20), 54.8 (C-40), 39.1 (C-1), 29.5 (C-3); HRMS (ESI): Calcd. for
C9H13ClO4: 220.0502. Found: 243.0405 [M þ Na]þ. Anal. Calcd. for
C9H13ClO4: C, 48.99; H, 5.94. Found C, 49.01; H, 5.93.
20-Acetyl-40-chloro-40-deoxy-b-D-galactosyl-propan-2-one-
30,60-ketal (4)
Compound 3 (150 mg, 0.68 mmol) was mixed with pyridine (1 mL), Ac2O
(0.5 mL), and a catalytic amount of DMAP. The mixture was stirred at
ambient temperature and monitored by TLC. After the disappearance of
starting sugar, absolute EtOH (2 mL) was added. The mixture was continued
to stir for 20 min, then partitioned by EtOAc and H2O. The EtOAc layer was
washed with water (5 mL ꢀ 2), dried over anhydrous Na2SO4, and evaporated,
affording compound 4 as an oil (167 mg, 94%): IR (KBr): 2939, 1744, 1367, 1213,
1
1187, 1056 cm21; H NMR (CDCl3, 400 MHz): d 4.92 (dd, 1H, J2 ,1 ¼ 2.0 Hz,
0
0
J2 ,3 ¼ 4.4 Hz, H-20), 4.63 (dd, 1H, J4 ,5 ¼ 2.8 Hz, J4 ,3 ¼ 6.4 Hz, H-40), 4.34
0
0
0
0
0
0

L. Yan et al.
344
(m, 1H, H-50), 4.30 (dd, 1H, J6 a,5 ¼ 4.4 Hz, J6 a,6 b ¼ 13.2 Hz, H-60a), 4.16
0
0
0
0
(m, 1H, H-30), 4.14 (dd, 1H, J1 ,2 ¼ 2.0 Hz, J1 ,1a ¼ J1 ,1b ¼ 3.2 Hz, H-10), 4.10
0
0
0
0
(d, 1H, J6 b,6 a ¼ 13.2 Hz, H-60b), 2.43 (dd, 1H, J1a,1 ¼ 3.2 Hz, J1a,1b
¼
0
0
0
0
15.2 Hz, H-1a), 2.16 (dd, 1H, J1b,1 ¼ 3.2 Hz, J1b,1a ¼ 15.2 Hz, H-1b), 2.16
(s, 3H, H-CH3), 1.54 (s, 3H, H-3); 13C NMR (CDCl3, 100 MHz): d 169.8
(C55O), 100.3 (C-2), 75.9 (C-50), 70.4 (C-20), 69.9 (C-30), 69.3 (C-60), 66.2 (C-10),
54.9 (C-40), 39.3 (C-1), 29.6 (C-3), 21.0 (C-CH3); HRMS (ESI): Calcd.
for C11H15ClO5: 262.0608. Found: 285.0510 [M þ Na]þ. Anal. Calcd. for
C11H15ClO5: C, 50.29; H, 5.76. Found C, 50.31; H, 5.78.
1-(b-D-Glucopyranosyl)-propan-2-one (7)
The compound was prepared from 5 in 96% yields under the conditions
described in 3.2. IR (KBr): 3422, 2912, 1706, 1363, 1085 cm21 1H NMR
;
(D2O, 400 MHz): d 3.76 (dd, 1H, J6a,5 ¼ 1.6 Hz, J6a,6b ¼ 12.4 Hz, H-6a), 3.70
0
0
(dt, 1H, J1,1 a ¼ 3.2 Hz, J1,1 b ¼ J1,2 ¼ 9.2 Hz, H-1), 3.59 (dd, 1H, J6b,5
¼
5.2 Hz, J6b,6a ¼ 12.4 Hz, H-6b), 3.40 (t, 1H, J ¼ 8.4 Hz, H-3), 3.33 (m, 1H,
0
H-5), 3.31 (m, 1H, H-4), 3.14 (t, 1H, J ¼ 9.2 Hz, H-2), 2.94 (dd, 1H, J1 a,1
¼
¼
2.8 Hz, J1 a,1 b ¼ 16.4 Hz, H-10a), 2.63 (dd, 1H, J1 b,1 ¼ 9.2 Hz, J1 b,1 a
0
0
0
0
0
13
16.4 Hz, H-10b), 2.19 (s, 3H, H-30); C NMR (D2O, 100 MHz): d 213.3 (C-20),
79.5 (C-5), 77.2 (C-3), 75.3 (C-1), 73.1 (C-2), 69.7 (C-4), 60.7 (C-6), 45.6 (C-10),
29.8 (C-30); HRMS (ESI): Calcd. for C9H16O6: 220.0947. Found: 243.0846
[M þ Na]þ. Anal. Calcd. for C9H16O6: C, 49.09; H, 7.32. Found C, 49.06; H, 7.34.
1-(b-D-Galacopyranosyl)-propan-2-one (8)
The compound was prepared from 6 in 92% yields under the conditions
similar to those described in 3.2. IR (KBr): 3381, 2923, 1706, 1364,
1
1088 cm21; H NMR (D2O, 400 MHz): d 3.85 (d, 1H, J4,3 ¼ 3.3 Hz, H-4), 3.63
0
0
(dt, 1H, J1,1 a ¼ 3.0 Hz, J1,1 b ¼ J1,2 ¼ 9.4 Hz, H-1), 3.58 (dd, 1H, J6a,5
¼
8.4 Hz, J6a,6b ¼ 11.0 Hz, H-6a), 3.55 (dd, 1H, J6b,5 ¼ 8.7 Hz, J6b,6a ¼ 11.0 Hz,
H-6b), 3.54 (m, 1H, H-5), 3.51 (m, 1H, H-3), 3.35 (t, 1H, J ¼ 9.4 Hz, H-2),
2.92 (dd, 1H, J1 a,1 ¼ 3.0 Hz, J1 a,1 b ¼ 16.7 Hz, H-10a), 2.64 (dd, 1H, J1 b,1
¼
0
0
0
0
9.4 Hz, J1 b,1 a ¼ 16.7 Hz, H-10b), 2.17 (s, 3H, H-30); 13C NMR (D2O,
100 MHz): d 213.4 (C-20), 78.5 (C-5), 75.6 (C-1), 73.8 (C-3), 70.4 (C-2), 69.1
(C-4), 61.1 (C-6), 45.7 (C-10), 29.7 (C-30); HRMS (ESI): Calcd. for C9H16O6:
220.0947. Found: 243.0860 [M þ Na]þ. Anal. Calcd. for C9H16O6: C, 49.09; H,
7.32. Found C, 49.11; H, 7.34.
0
0
b-D-Glucopyranosyl-propan-2-one-30,60-ketal (9)
The compound was prepared from 7 in 76% yields under the conditions
described in 3.3. IR (KBr): 3420, 2926, 1178, 1068 cm21 1H NMR (CDCl3,
;

Novel Caged Intramolecular Ketals
345
400 MHz): d 4.27 (d, 1H, J5 ,6 ¼ 4.4 Hz, H-50), 4.14 (m, 1H, H-40), 4.10 (m, 1H,
0
0
H-10), 4.05 (m, 1H, H-30), 4.02 (dd, 1H, J6 a,5 ¼ 4.4 Hz, J6 a,6 b ¼ 13.2 Hz,
0
0
0
0
H-60a), 3.93 (dd, 1H, J6 b,5 ¼ 4.4 Hz, J6 b,6 a ¼ 13.2 Hz, H-60b), 3.75 (m, 1H,
0
0
0
0
H-20), 2.44 (dd, 1H, J1a,1 ¼ 3.2 Hz, J1a,1b ¼ 15.6 Hz, H-1a), 2.13 (dd, 1H,
0
J1b,1 ¼ 3.2 Hz, J1b,1a ¼ 15.6 Hz, H-1b), 1.44 (s, 3H, H-3); 13C NMR (CDCl3,
0
100 MHz): d 99.9 (C-2), 78.7 (C-50), 69.7 (C-60), 69.3 (C-40), 69.1 (C-10), 67.9
(C-30), 66.6 (C-20), 39.1 (C-1), 29.5 (C-3); HRMS (ESI): Calcd. for C9H14O5:
202.0841. Found: 225.0737 [M þ Na]þ. Anal. Calcd. for C9H14O5: C, 53,46; H,
6.98. Found C, 53.45; H, 7.01.
b-D-Galactopyranosyl-propan-2-one-30,60-ketal (10)
The compound was prepared from 8 in 85% yields under the conditions
described in 3.3. IR (KBr): 3326, 2962, 1389, 1136, 1079 cm21 1H NMR
;
(CDCl3, 400 MHz): d 4.41 (d, 1H, J4 ,3 ¼ 6.5 Hz, H-40), 4.36 (d, 1H, J3 ,4
¼
0
0
0
0
6.5 Hz, H-30), 4.23 (t, 1H, J ¼ 2.6 Hz, H-10), 4.18 (t, 1H, J ¼ 5.3 Hz, H-50),
4.04 (m, 1H, H-20), 3.87 (dd, 1H, J6 a,5 ¼ 6.2 Hz, J6 a,6 b ¼ 11.2 Hz, H-60a),
0
0
0
0
3.77 (dd, 1H, J6 b,5 ¼ 4.6 Hz, J6 b,6 a ¼ 11.2 Hz, H-60b), 2.07 (dd, 1H, J1a,1
¼
0
0
0
0
0
0
2.3 Hz, J1a,1b ¼ 14.4 Hz, H-1a), 1.97 (dd, 1H, J1b,1 ¼ 3.3 Hz, J1b,1a ¼ 14.4 Hz,
H-1b), 1.49 (s, 3H, H-3); 13C NMR (CDCl3, 100 MHz): d 105.8 (C-2), 74.6
(C-40), 73.1 (C-30), 71.3 (C-10), 70.7 (C-50), 68.5 (C-20), 64.7 (C-60), 43.0 (C-1),
22.1 (C-3); HRMS (ESI): Calcd. for C9H14O5: 202.0841. Found: 203.0927
[M þ H]þ. Anal. Calcd. for C9H14O5: C, 53.46; H, 6.98. Found C, 53.48; H, 6.96.
20-O-Tosyl-40-chloro-40-deoxy-b-D-galactosyl-propan-2-one-
30,60-ketal (11)
Compound 3 (238 mg, 1 mmol) was dissolved in dry pyridine (1 mL) and
toluene 4-sulfonyl chloride (285 mg, 1.5 mmol) was added. The reaction
mixture was stirred at rt for 24 h. After the disappearance of starting sugar,
distilled water (2 mL) was added. The mixture was continued to stir for
20 min, then partitioned between EtOAc and H2O. The EtOAc layer was
washed with water (5 mL ꢀ 2), dried over anhydrous Na2SO4, and evaporated,
affording compound 11 as an oil (340 mg, 91%): IR (KBr): 2924, 1598, 1367,
1190, 1177 cm21
;
1H NMR (CDCl3, 400 MHz): d 7.82 (d, 2H, J ¼ 8.2 Hz,
H-Ar), 7.37 (d, 2H, J ¼ 8.2 Hz, H-Ar), 4.61 (m, 1H, H-40), 4.57 (dd, 1H,
J2 ,1 ¼ 2.5 Hz, J2 ,3 ¼ 6.6 Hz, H-20), 4.31 (m, 1H, H-50), 4.25 (dd, 1H, J6 a,5
¼
0
0
0
0
0
0
4.4 Hz, J6 a,6 b ¼ 13.6 Hz, H-60a), 4.05 (m, 3H, H-30, H-60b, H-10), 2.47 (s, 3H,
0
0
0
Ar-CH3), 2.40 (dd, 1H, J1a,1 ¼ 3.4 Hz, J1a,1b ¼ 15.4 Hz, H-1a), 2.18 (dd, 1H,
J1b,1 ¼ 2.9 Hz, J1b,1a ¼ 15.4 Hz, H-1b), 1.49 (s, 3H, H-3); 13C NMR (CDCl3,
0
100 MHz): d 146.0 (C-Ar), 133.8 (C-Ar), 130.6 (2C-Ar), 128.2 (2C-Ar), 100.6
(C-2), 76.4 (C-50), 76.3 (C-20), 70.4 (C-30), 69.7 (C-60), 66.9 (C-10), 54.4 (C-40),
40.1 (C-1), 29.9 (C-3), 22.1 (C-CH3); HRMS (ESI): Calcd. for C16H19ClO6S:

L. Yan et al.
346
374.0591. Found: 397.0484 [M þ Na]þ. Anal. Calcd. for C16H19ClO6S: C, 51.27;
H, 5.11. Found C, 51.30; H, 5.10.
1-(4-Chloro-4-deoxy-2-O-tosyl-b-D-galactopyranosyl)-
propan-2-one (12)
A mixture of ketal 11 (300 mg, 0.80 mmol), trifluoroacetic acid (0.5 mL),
and water (0.5 mL) was stirred at rt overnight. The solvents were evaporated
under diminished pressure. The residue was dissolved in EtOAc, and the
solution was washed with satd aq NaHCO3 (5 mL ꢀ 2) and water (5 mL ꢀ 3).
The organic layer was dried over anhydrous Na2SO4 and evaporated, affording
12 (295 mg, 94%) as an oil: IR (KBr): 3447, 2925, 1715, 1599, 1359, 1178 cm21
;
1H NMR (CDCl3, 400 MHz): d 7.83 (d, 2H, J ¼ 8.2 Hz, H-Ar), 7.36 (d, 2H,
J ¼ 8.2 Hz, H-Ar), 4.62 (t, 1H, J ¼ 9.4 Hz, H-2), 4.43 (d, 1H, J ¼ 3.6 Hz, H-4),
3.92 (m, 2H, H-5, H-3), 3.78 (m, 1H, H-1), 3.64 (dd, 1H, J6a,5 ¼ 7.2 Hz,
J6a,6b ¼ 11.6 Hz, H-6a), 3.11 (dd, 1H, J6b,5 ¼ 5.6 Hz, J6b,6a ¼ 11.6 Hz, H-6b),
2.73 (m, 2H, H-10), 2.46 (s, 3H, Ar-CH3), 2.15 (s, 3H, H-30); 13C NMR (CDCl3,
100 MHz): d 205.4 (C-20), 145.5 (C-Ar), 133.2 (C-Ar), 129.9 (2C-Ar), 128.1
(2C-Ar), 79.4 (C-5), 77.7 (C-2), 73.9 (C-1), 72.1 (C-3), 63.1 (C-4), 62.2 (C-6),
45.0 (C-10), 30.8 (C-30), 21.7 (C-CH3); HRMS (ESI): Calcd. for C16H21ClO7S:
392.0697. Found: 415.0580 [M þ Na]þ. Anal. Calcd. for C16H21ClO7S: C,
48.92; H, 5.39. Found C, 48.89; H, 5.40.
ACKNOWLEDGEMENTS
We are grateful to NNSF of P. R. China (No. 20572103) for financial support of
this work.
REFERENCES
[1] (a) Grindley, T.B. In Modern Methods in Carbohydrate Synthesis; Khan, S.H.,
O’Neill, R.A., Eds.; Harwood Academic: New York, 1996; 225–250;
(b) Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Chemistry, 3rd edn.;
John Wiley: New York, 1999; 17–254.
[2] Hanessian, S. Preparative Carbohydrate Chemistry; Marcel Dekker: New York,
1997.
[3] For examples, see: (a) Falck, J.R.; Muralikrishna, U.; Katipally, K.R.;
Capdevila, J.H.; Ulug, E.T. Concise syntheses of L-a-phosphatidyl-D-myo-inositol
3-phosphate (3-PIP), 5-phosphate (5-PIP), and 3,5-bisphosphate (3,5-PIP2). Tetra-
hedron Lett. 2000, 41, 4271–4275; (b) Painter, G.F.; Groove, S.J.A.; Gilbert, I.H.;
Holmes, A.B.; Raithby, P.R.; Hill, M.L.; Hawkins, P.J.; Stephens, L.R. General syn-
thesis of 3-phosphorylated myo-inositol phospholipids and derivatives. J. Chem.
Soc., Perkin Trans. 1 1999, 8, 923–936; (c) Biamonte, M.A.; Vasella, A. An advan-
tageous synthesis of 1D- and 1L-1,2,3,5/4-cyclohexanepentol. Helv. Chim. Acta
1998, 81, 688–694; (d) Das, T.; Shashidhar, M.S. Racemic 2,4-di-O-benzoyl-myo-

Novel Caged Intramolecular Ketals
347
inositol 1,3,5-orthoformate: a versatile intermediate for the preparation of myo-
inositol phosphates. Carbohydr. Res. 1998, 308, 165–168.
[4] (a) Angyal, S.J. Myo-inositol 4,6-carbonate: an easily prepared small molecule with
three syn-axial hydroxyl groups. Carbohydr. Res. 2000, 325, 313–320;
(b) Paquette, L.A.; Tae, J.; Gallucci, J.C. Synthesis and crystal structure of a
unique linear homoditopic ligand bifacially complexed to lithium picrate. Org.
Lett. 2000, 2, 143–146; (c) Tae, J.; Rogers, R.D.; Paquette, L.A. Lithium ion-selec-
tive binding properties of a conformationally constrained tris(spirotetrahydro-
furan) secured to an inositol orthoformate platform. Org. Lett. 2000, 2, 139–142;
(d) Tse, B.; Kishi, Y. Chiral analogs of enterobactin with hydrophilic or lipophilic
properties. J. Am. Chem. Soc. 1993, 115, 7892–7893.
[5] (a) Moore, R.E.; Bartolini, G.J. Structure of palytoxin. J. Am. Chem. Soc. 1981, 103,
2491–2494; (b) Usami, M.; Satake, M.; Ishida, S.; Inoue, A.; Kan, Y.; Yasumoto, T.
Palytoxin analogs from the dinoflagellate Ostreopsis siamensis. J. Am. Chem. Soc.
1995, 117, 5389–5390; (c) Suh, E.M.; Kishi, Y. Synthesis of palytoxin from paly-
toxin carboxylic acid. J. Am. Chem. Soc. 1994, 116, 11205–11206.
[6] (a) Sears, P.; Wang, C.-H. Intervention of carbohydrate recognition by proteins and
nucleic acids. Proc. Natl. Acad. Sci. U. S. A. 1996, 93, 12086–12093; (b) Witczak, Z.J.
Carbohydrates as drugs and potential therapeutics. Curr. Med. Chem. 1995, 1,
392–405.
[7] For leading reviews on C-glycoside synthesis: (a) Du, Y.; Linhardt, R.J.; Vlahov, I.R.
Recent advances in stereoselective C-glycoside synthesis. Tetrahedron 1998, 54,
9913–9959; (b) Togo, H.; He, W.; Waki, Y.; Yokoyama, M. C-Glycosidation technol-
ogy with free radical reactions. Synlett 1998, 7, 700–717; (c) Praly, J.-P. Structure
of anomeric glycosyl radicals and their transformations under reductive conditions.
Adv. Carbohydr. Chem. Biochem. 2000, 56, 65–151.
[8] Rodrigues, F.; Canac, Y.; Lubineau, A. A convenient, one-step, synthesis of b-C-gly-
cosidic ketones in aqueous media. Chem. Commun. 2000, 20, 2049–2050.
[9] Liu, F.-W.; Liu, H.-M.; Ke, Y.; Zhang, J.-Y. A facile approach to anhydrogalactosu-
crose derivatives from chlorinated sucrose. Carbohydr. Res. 2004, 339, 2651–2656.
[10] Liu, F.-W.; Zhang, Y.-B.; Liu, H.-M.; Song, X.-P. Preparation of a and b anomers of
1,2,3,6-tetra-O-acetyl-4-chloro-4-deoxy-D-galactopyranose based upon anomeriza-
tion and kinetic acetylation. Carbohydr. Res. 2005, 340, 489–495.