Regioselective 1-O-acyl hydrolysis of peracylated glycopyranoses by mercuric chloride and mercuric oxide

Article abstract of DOI:10.1055/s-2001-16084

A convenient synthetic method for regioselective 1-O-acyl hydrolysis of peracylated glycopyranoses into tetra-O-acylgly-copyranoses using mercuric chloride and mercuric oxide in aqueous acetone is described.

Full text of DOI:10.1055/s-2001-16084

1450
SHORT PAPER
Regioselective 1-O-Acyl Hydrolysis of Peracylated Glycopyranoses by
Mercuric Chloride and Mercuric Oxide
Regioselective
1
h
-
O
-Acyl
H
y
o
drolysis of
P
t
eracyla
a
ted
G
lycopyranos
S
es ambaiah,a Phillip E. Fanwick,b Mark Cushman*a
a
Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907, USA
Fax +1(765)4946790; E-mail: cushman@pharmacy.purdue.edu
b
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
Received 19 January 2001; revised 13 March 2001
reaction conditions, -D-galactose pentaacetate (7) also
reacted with HgO and HgCl2 to afford regio- and stereo-
selectively 2,3,4,6-tetra-O-acetyl- -D-galactopyranose
(8) in 71% yield (Scheme). In this case, the other epimer
was not detected in the crude reaction mixture neither by
1H NMR nor by TLC analysis. The structures of com-
pounds 2, 4, 6 and 8 were determined on the basis of ear-
lier reported data.4a,10,11 In all cases, 15–20% of the
starting material was recovered from the reaction mixture,
indicating that the deacylation reactions were indeed re-
gioselective.
Abstract: A convenient synthetic method for regioselective 1-O-
acyl hydrolysis of peracylated glycopyranoses into tetra-O-acylgly-
copyranoses using mercuric chloride and mercuric oxide in aqueous
acetone is described.
Key words: glycopyranoses, oligosaccharides, regioselectivity,
stereoselectivity, mercuric chloride
Fully protected sugars having one free hydroxyl group at
the anomeric carbon are versatile building blocks for the
synthesis of oligosaccharides and glycoconjugates.1 Sev-
eral methods for selective deprotection of C-1 acetates of
glycopyranoses are known in the literature. Some of them
involve a two-step reaction sequence in which in the first
step, D-glycopyranose pentaacetates are converted to un-
stable glycosyl halides, and in the second step, the halides
are hydrolyzed in the presence of expensive reagents like
silver carbonate or nitrate.2 Other methods involve regi-
oselective deacetylation at the anomeric position by using
bis(tributyltin)oxide,3 ammonia,4 butylamine,5 hydra-
zine,6 hydrazine acetate,7 piperidine,8 KCN/KOH,3 and
enzymes.9 Some of these procedures involve either highly
basic conditions3–8 or expensive reagents.2 Several of the
available methods also have severe drawbacks such as
side product formation8 and unstable intermediates such
as glycosyl halides.2 We now report a convenient method
for regioselective 1-O-acyl hydrolysis of peracylated gly-
copyranoses that is inexpensive, mild, and occurs at neu-
tral pH. The reaction is unprecedented, and was
discovered unexpectedly during our work on the use of
HgO and HgCl2 for hydrolysis of dithioacetals in carbohy-
drates.
AcO
AcO
AcO
AcO
HgO/HgCl2
70%
O
O
AcO
OAc
OAc
AcO
OH
OH
OAc
OAc
1
2
AcO
AcO
AcO
AcO
O
O
HgO/HgCl2
74%
OAc
OAc
3
4
tBuCOO
tBuCOO
HgO/HgCl2
60%
tBuCOO
tBuCOO
tBuCOO
O
O
tBuCOO
tBuCOO
OCOtBu
OH
tBuCOO
6
5
AcO
AcO
AcO
AcO
-D-Glucose pentaacetate (1) was reacted with yellow
HgO and HgCl2 in refluxing aqueous acetone for two
days. After purification, 2,3,4,6-tetra-O-acetyl-D-glu-
copyranose (2) was obtained in 70% yield ( : ratio
1:3.9) (Scheme). To define the scope of this new hydroly-
sis reaction, other sugars such as -D-ribopyranose-
1,2,3,4-tetraacetate (3) and D-galactose pentapivalate (5)
were also reacted with HgO and HgCl2 to provide the cor-
responding products 4 ( : ratio 5.3:1) and 6 ( : ratio
1:1) in 74% and 60% yields, respectively. Under similar
AcO
AcO
O
O
HgO/HgCl2
71%
OAc
OH
OAc
OAc
7
8
AcO
AcO
AcO
AcO
AcO
AcO
PhCOCl, Et3N
77%
O
O
O
OH
O
Ph
OAc
OAc
Synthesis 2001, No. 10, 30 07 2001. Article Identifier:
1437-210X,E;2001,0,10,1450,1452,ftx,en;M00301SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
8
9
Scheme

SHORT PAPER
Regioselective 1-O-Acyl Hydrolysis of Peracylated Glycopyranoses
1451
the CHCl3 layers were washed with sat. aq KI solution (2 60 mL)
and then H2O (50 mL), dried (Na2SO4), and concentrated. The re-
sulting residues were purified by flash chromatography (25 g, 3
40 cm column of silica gel, 230–400 mesh) eluting with hexanes–
EtOAc (60:40) to furnish the desired compounds 2, 4, 6 or 8 in 60–
74% yields. The structures of compounds 2,4a,10 4,4a 611 and 812 were
determined by comparing their spectral data with those reported
earlier.
As outlined above, a variety of methods are available for
the regioselective 1-O-deacylation of peracetylated glyco-
pyranoses.2–9 The yields reported for these methods range
from 30–100% and depend on the particular substrate, re-
agent, and conditions employed. The presently described
method does not offer a clear advantage in yield over the
reported procedures, but it does provide a method that is
carried out under neutral conditions, which may offer ad-
vantages in situations in which non-basic conditions
would be desirable.
2,3,4,6-Tetra-O-acetyl-1-O-benzoyl- -D-galactopyranose (9)
Benzoyl chloride (0.069 mL, 0.49 mmol) was added dropwise to a
well-stirred solution of 8 (0.17 g, 0.49 mmol) in Et3N (1.0 mL) and
anhyd CH2Cl2 (10 mL) at 0 ° C under nitrogen. The reaction mix-
ture was stirred at r.t. for 4 h, washed with H2O (2 10 mL), brine
(2 10 mL), dried (Na2SO4) and concentrated. The resulting residue
was purified by using flash chromatography (20 g, 2 40 cm col-
umn of silica gel, 230–400 mesh), eluting with hexane–EtOAc
(80:20), to furnish the desired compound 9 as a white crystalline
solid (0.17 g, 77%); mp 104–106°C.
The epimers of 2, 4, and 6 were extremely difficult to sep-
arate and configuration assignments at the C-1 anomeric
1
position were established by H NMR spectroscopy. The
stereochemistry at the anomeric carbon of 2,3,4,6-tetra-O-
acetyl- -D-galactopyranose (8) was unambiguously con-
firmed by single-crystal X-ray structure analysis (Figure)
of its benzoyl derivative 9 (Scheme). The and ratios of
2, 4, and 6 were determined by 1H NMR integration of the
C-1 protons.
IR (KBr): = 2962, 1750, 1223 cm–1.
1H NMR (500 MHz, CDCl3): = 8.04 (d, 2 H, J = 7.39 Hz), 7.58 (t,
1 H, J = 7.46 Hz), 7.44 (t, 2 H, J = 7.74 Hz), 5.88 (d, 1 H, J = 8.32
Hz), 5.52 (dd, 1 H, J = 8.39 Hz, 10.41 Hz), 5.46 (d, 1 H, J = 3.26
Hz), 5.16 (dd, 1 H, J = 3.37 Hz, 10.47 Hz), 4.14 (m, 3 H), 2.17 (s, 3
H), 2.03 (s, 3 H), 2.00 (s, 3 H), 1.97(s, 3 H).
In conclusion, we have demonstrated regioselective C-1
deacylation of fully acetylated glycopyranoses in good
yield by mercuric chloride and mercuric oxide. Our meth-
od is very mild, occurs under neutral conditions, utilizes
inexpensive reagents, and does not require anhydrous
conditions.
ESMS: m/z = 475 (MNa+).
Anal. Calcd for C21H24O11: C, 55.75; H, 5.35. Found: C, 55.62; H,
5.35.
Crystallographic Data for Compound 913
Crystals of compound 9 suitable for X-ray structure analysis were
obtained by crystallization from CH2Cl2 and hexane solution.
Melting points are uncorrected and were determined on Thomas
Hoover Melting Point Apparatus. The H NMR spectra were re-
1
corded on Gemini (300 MHz) and Bruker (500 MHz) spectrometers
with CDCl3 as solvent and TMS as internal standard. Microanalyses
were performed at the Purdue Microanalysis Laboratory and all val-
ues were within the 0.13–0.05 range of the calculated composi-
tions.
Data for 9: C21H24O11 (452.42), colorless; orthorhombic; space
group P212121: a = 9.3116 (3), b = 10.9783 (3), c = 21.7691 (7) Å;
V = 2225.4 (2) Å3, Z = 4; Dc = 1.350 g cm–3. Preliminary examina-
tion and data collection were performed with Mo K radiation
( = 0.71073 Å) on a Nonius KappaCCD at 150 K. 14143 reflec-
tions were collected, of which 5026 were unique. Data were collect-
ed to a maximum 2 of 54.9°. The structure was solved by direct
methods using SIR.14 All remaining atoms were located in succeed-
ing difference Fourier syntheses. Hydrogen atoms were included in
the refinement but restrained to ride on the atom to which they are
bonded. The structure was refined in full-matrix least-squares
where the function minimized was w(|Fo|2 – |Fc|2)2 and the weight
w is defined as w = 1/[ 2(Fo2) + (0.0378P)2 + 0.4390P] where
1-O-Acyl Hydrolysis of Peracylated Glycopyranoses 1, 3, 5 and
7; General Procedure
Peracylated glycopyranose 1, 3, 5 or 7 (4.34 mmol) in acetone and
H2O (40:10 mL) was stirred at r.t. with yellow HgO (4.88 g, 22.52
mmol) while a solution of HgCl2 (4.40 g, 16.20 mmol) in acetone
(20 mL) was added dropwise. The reaction mixture was heated at
reflux for 2 d, cooled to r.t., filtered through Celite, and concentrat-
ed in vacuo. The residue was extracted with CHCl3 (3 100 mL),
Figure ORTEP diagram of 9
Synthesis 2001, No. 10, 1450–1452 ISSN 0039-7881 © Thieme Stuttgart · New York

1452
T. Sambaiah et al.
SHORT PAPER
P = (Fo2 + 2Fc2)/3. R1 = 0.039, wR2 = 0.089, goodness of fit = 1.028.
The highest peak in the final difference Fourier had a height of 0.20
e/A3. The minimum negative peak had a height of –0.22 e/A3. The
factor for the determination of the absolute structure15 refined to
0.00. Refinement was performed on a Alpha Server 2100 using
SHELX-97.16 Crystallographic drawings were done using programs
ORTEP17 and PLUTON.18
(7) Excoffier, G.; Gagnaire, D.; Utille, J.-P. Carbohydr. Res.
1975, 39, 369.
(8) Rowell, R. M.; Feather, M. S. Carbohydr. Res. 1967, 4, 486.
(9) (a) Hennen, W. J.; Sweers, H. M.; Wang, Y.-F.; Wong, C.-
H. J. Org. Chem. 1988, 53, 4939. (b) Bastida, A.;
Fernandez-Lafuente, R.; Fernandez-Lorente, G.; Guisan, J.
M. Bioorg. Med. Chem. Lett. 1999, 9, 633.
(10) Soli, E. D.; Manoso, A. S.; Patterson, M. C.; DeShong, P. J.
Org. Chem. 1999, 64, 3171.
(11) Laschat, S.; Kunz, H. J. Org. Chem. 1991, 56, 5883.
(12) Excoffier, G.; Gagnaire, D.; Utille, J.-P. Carbohydr. Res.
1975, 39, 369.
Acknowledgement
This research was made possible by NIH Grant GM51469.
(13) Selected bond lengths (Å) and angles (°) of 9: O(1)–C(2)
1.409(2), O(21)–C(2) 1.420(2), O(31)–C(3) 1.444(2),
O(41)–C(4) 1.442(2), O(51)–C(5) 1.441(2), C(6)–C(61)
1.521(3), O(21)–C(22) 1.363(2), C(3)–C(2) 1.515(2), O(1)–
C(2)–O(21) 107.36(14), O(1)–C(2)–C(3) 105.04(14), O(1)–
C(6)–C(5) 110.38(14), O(41)–C(4)–C(5) 110.35(14), C(3)–
C(4)–C(5) 110.70(14), C(22)–O(21)–C(2) 118.03(13),
C(32)–O(31)–C(3) 117.58(13), C(42)–O(41)–C(4)
118.69(13), C(2)–O(1)–C(6) 111.21(13).
(14) Altomare, A.; Cascarano, G.; Giacovazzo, C.; Guagliardi,
A.; Cascarano, G. L.; Moliterni, A. G. G.; Burla, M. C.;
Polidori, G.; Camalli, M.; Spagna, R. J. Appl. Crystallogr.
1999, 32, 115.
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Synthesis 2001, No. 10, 1450–1452 ISSN 0039-7881 © Thieme Stuttgart · New York