Preparation of sucrose heptaesters unsubstituted at the C-1 hydroxy group of the fructose moiety via selective O-desilylation

Article abstract of DOI:10.1016/S0008-6215(00)00119-1

Selective O-desilylation of 6,1',6'-tri-O-tert-butyldiphenylsilyl- 2,3,4,3',4'-penta-O-benzoylsucrose with hydrofluoric acid in acetonitrile led to the 1'-O-tert-butyldiphenylsilyl derivative (96% yield), which was further perbenzoylated and deprotected at OH-1' with tetrabutylammonium fluoride (86%). An analogous sequence with the corresponding O-acetylated sucrose derivative and tetrabutylammonium fluoride as desilylating agent resulted in a lower yield of the C-1' hydroxy derivative. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0008-6215(00)00119-1

www.elsevier.nl/locate/carres
Carbohydrate Research 328 (2000) 419–423
Note
Preparation of sucrose heptaesters unsubstituted at the
C-1 hydroxy group of the fructose moiety via selective
O-desilylation
M. Teresa Barros a,b,*, Christopher D. Maycock c, Christine Thomassigny c
a Instituto de Biologia Experimental e Tecnolo´gica, Apartado 12, P-2780 Oeiras, Portugal
b Departamento de Quimica, Faculdade de Ciencias e Tecnologia, Uni6ersidade No6a de Lisboa,
P-2825-114 Monte da Caparica, Portugal
c Instituto de Tecnologia Quimica e Biologia, Uni6ersidade No6a de Lisboa, Rua da Quinta Grande 6, Apartado 127,
P-2780 Oeiras, Portugal
Received 3 January 2000; received in revised form 18 April 2000; accepted 18 April 2000
Abstract
Selective O-desilylation of 6,1%,6%-tri-O-tert-butyldiphenylsilyl-2,3,4,3%,4%-penta-O-benzoylsucrose with hydrofluoric
acid in acetonitrile led to the 1%-O-tert-butyldiphenylsilyl derivative (96% yield), which was further perbenzoylated
and deprotected at OH-1% with tetrabutylammonium fluoride (86%). An analogous sequence with the corresponding
O-acetylated sucrose derivative and tetrabutylammonium fluoride as desilylating agent resulted in a lower yield of the
C-1% hydroxy derivative. © 2000 Elsevier Science Ltd. All rights reserved.
Keywords: Sucrose; 1%-Hydroxy sucrose; Sucrose heptaester; Selective (de)silylation
deacylation of the octaacetylsucrose, or by
multistep synthesis. Deacylation, however,
was not very selective and the desired product
normally had to be separated from a number
of regioisomers. As a consequence, the global
yields for these processes remained very low
(from 11% to inseparable isomers) and unsuit-
able for large scale preparations. The multi-
step sequence reported by Li and Wu [11] is
an example of the other approach. We wished
to develop a short and easy route for the
preparation of larger quantities of our target
molecule.
As part of a program directed toward the
valorisation of sucrose by incorporating it into
polymers, its conversion to natural com-
pounds and its possible application as a chiral
auxilliary in selective asymmetric cycloaddi-
tion [1,2], we needed to obtain a derivative of
sucrose, which we could functionalise easily at
the primary hydroxyl at C-1 of the fructose
moiety. A review of the literature revealed
that heptaprotected sucrose derivatives with a
free 1%-OH have been prepared [3–11]. In par-
ticular 2,3,4,6,3%,4%,6%-hepta-O-acetyl-sucrose
has been obtained [6–11] either by partial
We concluded that a possible route to com-
pounds such as 2,3,4,6,3%,4%,6%-hepta-O-ben-
zoyl-sucrose
could
involve
selective
* Corresponding author. Fax: +351-212-948550.
E-mail address: mtbarros@dq.fct.unl.pt (M.T. Barros).
silylation/desilylation of sucrose [12,13], based
0008-6215/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00119-1

420
M.T. Barros et al. / Carbohydrate Research 328 (2000) 419–423
six protons — to the methylenic protons 6, 1%
and 6%. A comparison of these values with
those in compound 1 showed no remarkable
variations of chemical shift, which indicates
the absence of migration of a benzoyl sub-
stituent to a primary hydroxy group. It was
impossible at this time to be precise about the
position of the silyloxy substituent (6, 1% or
6%-position). In order to determine its position,
we transformed 2 into its heptabenzoate
derivative 3 by acylation with benzoyl chloride
on the fact that the primary alcohol groups
are more reactive than the secondary and that
between the primary hydroxyls there is a rela-
tively well defined reactivity [14–17].
Our synthetic scheme was based upon a
selective deprotection of the hydroxyl func-
tions at the 6- and 6%-positions of the tri-tert-
butyldiphenylsilyl derivative 1 [17] (Scheme 1).
No desilylation occurred using an excess of
tetrabutylammonium fluoride either in
aqueous solution or under anhydrous condi-
tions in THF. Trimethylpyridinium fluoride in
THF, or heating with sodium hydroxide (5 N)
were also ineffective. Use of boron trifluoride
diethyl etherate for this purpose led to a mix-
ture of products. Only 40% hydrofluoric acid
in aqueous acetonitrile for a period 60 h at
room temperature afforded the dihydroxysu-
crose derivative 2 in excellent yield (96%). In
1
in pyridine (quantitative yield). Its H NMR
spectral data (300 MHz, CDCl3) showed in
particular the presence of two doublets (AB
system, 3.67 and 4.06 ppm, J 10.5 Hz, one
proton each) that we have attributed to the
H-1% protons. The H-6 protons (4.30 and 4.36
ppm, two doublet of doublet) and H-6% pro-
tons (4.63 ppm, multiplet) have also been
assigned. These chemical shifts were in agree-
ment with structure 3, which contains the
ether protecting group at C-1 of the fructose
moiety, and has allowed us to determine the
structure of 2 as the 2,3,4,3%,4%-penta-O-ben-
zoyl-1%-O-tert-butyldiphenylsilylsucrose. Com-
pound 3 was then selectively deprotected us-
ing 2.0 equivalents of tetrabutylammonium
fluoride in THF, leading to the expected com-
pound 4 (86%) without migration. A study of
1
the H NMR spectrum (300 MHz, CDCl3) of
2, we note the presence of a singlet at 1.02
ppm integrating for nine protons correspond-
ing to the tert-butyl group of the silyloxy
function and a broad singlet at 2.68 ppm (two
hydroxylic protons), which indicated the pres-
ence of only one tert-butyldiphenylsilyl group.
Furthermore, we have attributed (Table 1) the
multiplet at 3.95–3.50 ppm — integration
1
its H NMR spectral data revealed two dou-
blets at 3.59 and 3.80 ppm (one proton each,
J 12.3 Hz) attributed to H-1% a to a hydroxyl
group. As this last product was very difficult
to purify and satisfactory microanalytical or
mass spectrometric data could not be ob-
tained, it has been characterised as its 1%-O-
acetyl derivative 5, which afforded the
necessary analytical data.
A similar sequence from the 6,1%,6%-tri-O-si-
lyl-2,3,4,3%,4%-penta-O-acetyl sucrose (6) [17]
led to the compound 7 after selective O-desily-
lation using tetrabutylammonium fluoride in
THF, followed by peracetylation. Unfortu-
nately, some O-deacetylation occurred and the
best yield of 7 was obtained by using 2.7
equivalents of reagent during a short period,
which afforded 54% yield in two steps. A
selective deprotection of the remaining tert-
butyldiphenylsilyl group gave the expected 8
(71%), whose physical data (optical rotation
Scheme 1. (i) aq HF, MeCN; (ii) BzCl/DMAP/pyridine; (iii)
nBu4NF, THF; (iv) Ac2O/DMAP/pyridine; (v) (1) nBu4NF,
THF; (2) Ac2O/DMAP/pyridine.
1
and H NMR data) were identical to those

M.T. Barros et al. / Carbohydrate Research 328 (2000) 419–423
421
Table 1
1H NMR spectral data (CDCl3, 300 MHz): chemical shifts (l in ppm) and coupling constants (Hz) a
1 [17]
2
3
4
5
6 [17]
7
H-1
H-2
H-3
H-4
H-5
H-6
m 5.96 c
m 5.34 c
m 5.96
m 5.96
m 4.25
d 3.54
d 3.41
d 4.03
d 3.65
d 6.24
m 5.96
m 4.41
m 3.91
d 5.93
dd 5.23
t 6.04
t 5.46
d 4.37
m
m 6.04
dd 5.30
m 6.04
t 5.71
m 4.63
dd 4.36
dd 4.30
d 4.06
d 3.67
d 6.36
m 6.04
m 4.63
m 4.63
m 6.05
dd 5.38
m 6.05
t 5.75
m 4.70
m 4.70 or d 4.45
d 6.13
dd 5.42
t 6.20
s 5.56 c
d 4.85 c
m 5.35
m 5.35
m 3.98
m 3.53
d 5.55
dd 4.77
t 5.28
t 5.76
t 4.96
m 4.67
dd 4.42
dd 4.32
d 4.71
d 4.56
d 5.95
t 5.89
m 4.24
m 4.20
d 4.04
d 3.66
d 3.40
d 5.86
t 5.38
3.95–3.50
m 3.95–3.50
H-1%
d 3.80
d 3.59
d 5.95
m 6.05
m 4.70
m 4.70
or d 4.45
3.6
m 3.79
m 3.53
d 5.84 c
m 5.35
m 4.12
m 3.79
H-3%
H-4%
H-5%
H-6%
d 6.37
t 6.11
d 4.23
m
3.95–3.50
3.0
m 4.27
m 4.27
m 4.17
m 4.20
J1,2
3.6
3.4
4.0
J2,3
J3,4
J4,5
J3%,4%
J4%,5%
J5,6a
J5,6b
J6,6
9.9
9.9
9.9
7.5
10.2
10.0
10.0
7.2
10.5
9.6
9.6
5.1
10.4
9.9
9.9
5.8
5.3–5.6
2.5
3.2
12.6
12.0
7.2
4.5
10.0
10.0
10.0
7.0
7.0
8.4
7.0
2.7
3.0
12.3
10.5
10.5
10.0
9.3 b
12.3
11.0
11.0
J1%,1%
a Key: s, singlet; d, doublet; dd, double doublet; t, triplet; m, multiplet.
b J6,6 or J6%,6%
.
c Value in agreement with the literature.
described in the literature [7,8,10], and unre-
acted 7 (29%). Attempts to increase the pro-
portion of these two compounds in favour of
8 have failed because more forcing conditions
result in partial removal of the acetate groups.
In summary, we have obtained the novel
1%-OH free heptabenzoyl sucrose derivative 4
via a short sequence (five steps from sucrose)
with an overall yield of 66%. The flexibility of
this pathway allows us to easily change the
protecting groups, as has been shown by the
preparation of its heptaacetate homolog 8
(overall yield 35%), and makes possible the
selective preparation of several monohydroxy
sucrose esters or ethers.
under reduced pressure. Optical rotations
were measured at 20 °C on a Perkin–Elmer
241 polarimeter (1 dm cell). Column chro-
matography was carried out using Silica Gel
60 H, 60 GF254 or 60M (230–400 mesh).
Thin-layer chromatography (TLC) was per-
formed on E. Merck 60 F254 plates and com-
pounds were visualised with a soln of 30%
H2SO4 in EtOH or a soln of phosphomolyb-
dic acid (25 g) in EtOH (500 mL) and heat-
ing, or under UV light. Organic solvents were
dried immediately before use. Anhydrous
1
MgSO4 was used to dry organic extracts. H
NMR spectra were recorded on a Bruker
AMX 300 MHz. Microanalyses were per-
formed by the Microanalytical Services of the
Centre National de la Recherche Scientifique
(CNRS), F-69390 Vernaison, France.
1. Experimental
1-O-tert-Butyldiphenylsilyl-3,4,6-tri-O-ben-
zoyl-i-
zoyl-h-
1 [17] (300.0 mg, 0.2 mmol) dissolved in
D
-fructofuranosyl-2,3,4,6-tetra-O-ben-
General methods.—Melting points were
determined on a Bu¨chi 530 apparatus and are
not corrected. Evaporations were performed
D-glucopyranoside (3).—To compound

422
M.T. Barros et al. / Carbohydrate Research 328 (2000) 419–423
began to appear (TLC in 1:4 EtOAc–hex-
ane), the solution was rapidly concentrated
and the obtained syrup (5.1 g) was dissolved
in pyridine (10 mL). DMAP (100 mg) and
Ac2O (447.0 mL, 4.0 equiv) were added. After
one night at rt, the solution was poured onto
ice and NaHCO3, and extracted with CH2Cl2.
Concentration of the dried solution led to a
syrup, whose purification under silica gel (1:2
EtOAc–hexane) gave 7 as white crystals
(560.0 mg, 54% in two steps): mp 49–50 °C;
[h]D +44.7° (c 0.6, CHCl3); Anal. Calcd for
C42H54O18Si: C, 57.66; H, 6.22. Found: C,
57.55; H, 6.10.
MeCN (8 mL) was added 0.1 mL of HF
(40% HF in water). After 2 days of stirring
at rt, satd NaHCO3 was added until neutral
pH, the aq layer was extracted with CH2Cl2
and the combined organic layers were dried
and concentrated to a yellow oil (295 mg). A
purification by preparative TLC (1:2 ace-
tone–hexane) gave 1-O-tert-butyldiphenylsi-
lyl-3,4-di-O-benzoyl-b-
D-fructofuranosyl-2,3,4-
tri-O-benzoyl-a- -glucopyranoside (2) (200
D
mg, 96%). Compound 2 (200.0 mg, 0.18
mmol) was dissolved in pyridine (1.5 mL),
and DMAP (50 mg) and benzoyl chloride
(84.0 mL, 4.0 equiv) were added. After one
night at rt, the solution was poured into ice
and NaHCO3, extracted with CH2Cl2, and
dried. Concentration of the solution gave a
syrup, which was purified by preparative
TLC (1:2 acetone–hexane), yielding 3 (238.0
mg, 100%): [h]D +16.6° (c 0.5, CHCl3);
Anal. Calcd for C77H68O18Si: C, 70.63; H,
5.23. Found: C, 70.99; H, 5.98.
3,4,6 - Tri - O - acetyl - i -
D
- fructofuranosyl-
- glucopyranoside
2,3,4,6 - tetra - O - acetyl - h -
D
(8).—To compound 7 (100.0 mg, 0.11 mmol)
in dry THF (3 mL) and under nitrogen was
added Bu4NF (30.0 mg, 1.0 equiv.). After 30
min at rt, THF was evaporated and the
crude product (244.0 mg) was purified by sil-
ica gel chromatography (2:1 EtOAc–hexane)
affording unreacted 7 (29 mg, 29%) and 8
(foam, 52.0 mg, 71%): [h]D +33.7° (c 0.5,
CHCl3), lit. +38.5° (c 1, CHCl3) [7], lit. +
50.2° (c 1.0, CHCl3) [8], lit. +43° (c 2,
CHCl3) [10]; Anal. Calcd for C26H36O18: C,
49.06; H, 5.70. Found: C, 49.20; H, 5.57.
1-O-Acetyl-3,4,6-tri-O-benzoyl-i-
furanosyl-2,3,4,6-tetra-O-benzoyl-h-
D
-fructo-
D-glucopy-
ranoside (5).—To compound 3 (140.0 mg,
0.11 mmol) in dry THF (1.5 mL) was added
Bu4NF (56.0 mg, 2.0 equiv) under nitrogen.
After 4 h, the solvent was evaporated and the
crude product was purified by silica gel chro-
matography (2:1 acetone–hexane), leading to
Acknowledgements
the 3,4,6-tri-O-benzoyl-b-
D
-fructofuranosyl-
2,3,4,6-tetra-O-benzoyl-a-
D
-glucopyranoside
This work has been supported by NATO
SFS (PO-SUGARS) and the FCT (grant
PRAXIS XXI/BPD/16348/98). We thank the
service of NMR of the Universidade Nova de
Lisboa for 2D NMR experiments. Some ex-
periments were carried out initially by Joana
Fonseca whom we thank.
(4: 98.5 mg, 86%).
Acetylation of 4 (98.5 mg, 0.09 mmol) was
achieved by dissolution in pyridine (1 mL)
and addition of DMAP (20 mg) and Ac2O
(12.9 mL, 1.5 equiv). After one night of stir-
ring, the reaction mixture was poured on ice
and NaHCO3 solution, extracted with
CH2Cl2, and dried. A purification of the con-
centrated extracts by flash chromatography
(1:3 EtOAc–hexane) afforded sirupy 5 (86.0
mg, 84%): [h]D +38.3° (c 1, CHCl3); Anal.
Calcd for C63H52O19: C, 67.98; H, 4.71.
Found: C, 67.98; H, 4.70.
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