A simple synthesis of D-galactono-1,4-lactone and key building blocks for the preparation of galactofuranosides

Article abstract of DOI:10.1080/07328303.2011.616273

The oxidation of D-galactose by Br₂ to yield D-galactono-1,4-lactone was developed and applied to the preparation of key building blocks for the synthesis of galactofuranosides. Three D-galactono-1,4-lactone derivatives protected as acetates, TBDMS ether, or acetonide were directly obtained in two steps on multigram scale with only one purification step. A mild deacetylation methodology afforded pure D-galactono-1,4-lactone and a new reduction of the lactone functionality using K-selectride was also optimized.

Full text of DOI:10.1080/07328303.2011.616273

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A Simple Synthesis of D-Galactono-1,4-
Lactone and Key Building Blocks for the
Preparation of Galactofuranosides
Vincent Lemau de Talancé a , Emilie Thiery a , Guillaume Eppe a ,
Sandy El Bkassiny a , Jérémie Mortier a & Stéphane P. Vincent a
a University of Namur (FUNDP), Académie Louvain, Département de
Chimie, Laboratoire de Chimie Bio-Organique, rue de Bruxelles 61,
B-5000, Namur, Belgium
Published online: 14 Dec 2011.
To cite this article: Vincent Lemau de Talancé , Emilie Thiery , Guillaume Eppe , Sandy El Bkassiny ,
Jérémie Mortier & Stéphane P. Vincent (2011): A Simple Synthesis of D-Galactono-1,4-Lactone and Key
Building Blocks for the Preparation of Galactofuranosides, Journal of Carbohydrate Chemistry, 30:7-9,
605-617
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Journal of Carbohydrate Chemistry, 30:605–617, 2011
ꢀ
C
Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2011.616273
A Simple Synthesis
of D-Galactono-1,4-Lactone
and Key Building Blocks
for the Preparation
of Galactofuranosides
Vincent Lemau de Talance´, Emilie Thiery, Guillaume Eppe,
Sandy El Bkassiny, Je´re´mie Mortier, and Ste´phane P. Vincent
University of Namur (FUNDP), Acade´mie Louvain, De´partement de Chimie,
Laboratoire de Chimie Bio-Organique, rue de Bruxelles 61, B-5000, Namur, Belgium
The oxidation of D-galactose by Br2 to yield D-galactono-1,4-lactone was developed and
applied to the preparation of key building blocks for the synthesis of galactofurano-
sides. Three D-galactono-1,4-lactone derivatives protected as acetates, TBDMS ether,
or acetonide were directly obtained in two steps on multigram scale with only one pu-
rification step. A mild deacetylation methodology afforded pure D-galactono-1,4-lactone
and a new reduction of the lactone functionality using K-selectride was also optimized.
Keywords Lactone; Galactofuranose; Arabinogalactan; Anomeric oxidation
INTRODUCTION
D-Galactofuranose (Galf), the thermodynamic less stable form of D-galactose,
is a major component of bacterial glycoconjugates, including severe pathogens
such as Mycobacterium tuberculosis and Klebsiella pneumoniae.[1] Galacto-
furanosides have also been found in parasites and eukaryotes but never in
mammals.[2] Therefore, the enzymes responsible for the biosynthesis of
galactofuranosides have become major targets for developing novel antibac-
terial agents.[3,4] Thus, the efficient and selective access to galactofuranosides
from the corresponding pyranose is highly desirable to allow the preparation
Received June 6, 2011; accepted August 17, 2011.
Address correspondence to Ste´phane P. Vincent, University of Namur (FUNDP),
Acade´mie Louvain, De´partement de Chimie, Laboratoire de Chimie Bio-Organique, rue
de Bruxelles 61, B-5000 Namur, Belgium. E-mail: stephane.vincent@fundp.ac.be
605

V. Lemau de Talance´ et al.
606
OH
O
OH
O
OR
O
OAc
O
O
O
O
OAc
HO
RO
AcO
O
OH
O
OR
OAc
OH
OH
OR
OAc
1
2
3, R = TBDMS
4, R = Ac
5
Figure 1: D-Galactono-1,4-lactone and derivatives.
of, for instance, bacterial cell wall fragments,[5] UDP-Galf,[6–8] the biosynthetic
precursor of natural galactofuranosides, or glycomimetics based on the Galf
scaffold.[9]
Under specific conditions, galactofuranosides can be obtained in good
yields directly from D-galactose, either through benzoylation[10,11] or under
Fischer glycosylation conditions.[8,12,13] Additionally, galactofuranosides have
been obtained from glycosyl acyclic dithioacetal[5,14] and by direct allylation
of D-galactose in DMPU.[15] On the other hand, D-galactono-1,4-lactone (or γ-
galactonolactone) 1 (Fig. 1) has been widely used as starting material for many
applications.[10,16–18] In our laboratory, lactone 1 was exploited as starting ma-
terial for the construction of inactivators and conformational probes of UDP-
galactopyranose mutase (UGM), a key enzyme involved in the mycobacterial
cell wall biosynthesis.[19,20]
A new robust and cheap synthesis that can provide multigram quantities
of D-galactono-1,4-lactone 1 is therefore highly desired. Here we report a novel
simple synthesis of lactone 1 from D-galactose and its transformation to key
building blocks 2–5 (Fig. 1), ready for further derivatization into galactofura-
nosides.
RESULTS AND DISCUSSION
The first synthesis of 1 was based on the reduction of galacturonic salt by
sodium borohydride followed by lactonization.[21] In 1974, Kurz et al. described
an elegant preparation of 1 based on enzymatic reactions.[22] Later, Vekemans
et al. described the direct oxidation of D-galactose under a controlled pressure
of oxygen in aqueous sodium hydroxide solution in the presence of palladium
on charcoal.[23] The technical difficulty of this synthesis is to maintain a con-
stant pH and a constant oxygen pressure.[24] The gamma−D−galactonolactone
1 was also prepared by hydrolysis of D-galactose N,Nꢁ-diphenylformazan that
requires a preliminary multistep synthesis.[25] Another strategy consists of
the methanolysis of 2,3,4,6-tetra-O-acetyl-1-bromo-β-D-galactopyranosyl chlo-
ride, to give quantitatively galactonolactone 1.[26] In this case, the starting
1,1-dihalogenated galactopyranoside is not easily accessible. Interestingly, the

Synthesis of D-Galactono-1,4-Lactone
607
catalytic hydrogen transfer using RhH(PPh3)4/benzalacetone[27,28] or the cou-
ple Shvo’s catalyst/cyclohexanone[29] was also successfully used. Overall, these
methods require either multistep synthesis or costly reagents. Therefore, other
simple and scalable methodologies, not yet explored with galactose, seemed at-
tractive to us.
One of the earliest techniques described for the preparation of δ- or γ-
lactones from free carbohydrates is the oxidation by bromine performed in
aqueous buffers. This method yields either aldonic acids[30] or lactones.[31] For
instance, D-mannono-1,4-lactone was quantitatively synthesized by oxidation
of D-mannose with an excess of bromine in the presence of sodium bicarbon-
ate in water.[32] El Ashry et al. explored a microwave-assisted oxidation pro-
tocol to prepare D-glucono-1,4-lactone.[33] D-glucose was treated with a large
excess of bromine in the presence of calcium chloride and calcium carbon-
ate in water under microwave irradiation. The D-gluconic acid thus formed
was then irradiated in methanol with catalytic hydrochloric acid to obtain D-
glucono-1,4-lactone (37% yield over two steps). Moreover, oxidation of D-ribose
with bromine in the presence of sodium bicarbonate in water was described
by Townsend and collaborators.[34] In this case, an excess of bromine was not
necessary to form quantitatively D-ribonolactone. After extraction by ethanol,
the formed ribonolactone was not isolated, but directly engaged in a protection
reaction.
Based on the literature data, we decided to develop a procedure based on
bromine oxidation, which had no precedent for D-galactose. Since our goal was
the access of lactone 1 in a multigram quantity, we did not follow a procedure
using microwave irradiation to avoid scale-up problems.
Oxidation of D-galactose with bromine in the presence of sodium bicarbon-
ate or calcium chloride and carbonate in water was complete in 3 days, regard-
less of bromine quantity used (1.05 to 3.5 equivalents). The most attractive
procedure used 1.05 equivalents of bromine and 2.0 equivalents of bicarbon-
ate (Sch. 1). On a large scale (20 g of D-galactose), we observed that clean
reactions require a slow addition of bromine into the galactose solution. The
NMR spectra of the crude reaction mixture at the end of the reaction showed
only trace amounts of impurities. In some cases, especially on small scales, the
NMR data were identical to those of authentic samples. However, purification
of lactone 1 happened to be more difficult than expected. Although described
Scheme 1: Synthesis of D-galactono-1,4-lactone.

V. Lemau de Talance´ et al.
608
in the literature on related sugar lactones, the purification by silica gel column
chromatography was not satisfactory in terms of yield and/or quality of the fi-
nal analytical data, whatever the eluent system. Moreover, recrystallization in
ethanol or iso-propanol did not provide satisfactory yields. Disappointingly, the
direct conversion of the crude galactonolactone 1 into acetonide 2 or peracetate
4 was not successful. This lack of reactivity may be due to the presence of salts
generated during the oxidation.
Therefore, we developed an extraction procedure to carry on the purifica-
tion and the derivatization from D-galactonolactone 1. Choosing an appropri-
ate solvent was essential to extract the product without contaminating salts.
D-Galactono-1,4-lactone was poorly soluble in acetone, iso-propanol, and ace-
tonitrile. Refluxing the crude mixture in iso-propanol led to isomerization into
the 1,5-lactone; thus, a mixture of δ- and γ-galactonolactone was obtained. Ab-
solute ethanol was eventually found to be the most efficient extraction solvent.
It is important to note that the extraction led to partial formation of the corre-
sponding ethyl ester, even if the mixture was neutralized at pH = 7. An acidic
hydrolysis quantitatively afforded the expected compound 1 (Sch. 1). From 20
g of D-galactose we could isolate 18.6 g of 1 following this protocol, which would
correspond to a yield of 94%. However, we have to mention that, although NMR
data perfectly matched those of authentic lactone 1, the m.p. value did not cor-
respond to the expected value, thus showing that some inorganic impurities
were still present after extraction. On the other hand, the quality of the ma-
terial was sufficient to allow the derivatization into the key intermediates 2–5
(Sch. 2), for which the yields will be given for two steps from D-galactose. Bases
with another countercation that could give a poorly soluble bromide salt and
make purification easier were thus considered and the same procedure was
reproduced with KHCO3 in place of NaHCO3.a However, less intermediate ma-
terial than expected was recovered and the overall yield was lower.
As we have shown previously,[4,19,20] the 5,6-isopropylidene-D-
galactonolactone 2 (Sch. 2) is a key intermediate for the generation of
conformational probes of enzymatic reactions and inhibitors of therapeutically
relevant enzymes. Many conditions can be envisaged to produce 2 from 1.
D-galactono-1,4-lactone 1 can be treated with iso-propenyl methyl ether in the
presence of p-toluenesulfonic acid in DMF,[35] with 2,2-dimethoxypropane
in the presence of p-toluenesulfonic acid in dry acetone,[16] with 2,2-
dimethoxypropane in the presence of Amberlite IR 120 (H+) in DMF,[18]
or in the presence of anhydrous copper sulfate or catalytic sulfuric acid in
dry acetone.[36,37] Catalysis by anhydrous stannous chloride was also reported
with dimethoxypropane in boiling 1,4-dioxane.[23] According to the protocol
developed by Toone et al., D-galactonolactone 1 was treated by catalytic
aWe thank one of the referees for this interesting suggestion.

Synthesis of D-Galactono-1,4-Lactone
609
Scheme 2: Protection reaction from D-galactono-1,4-lactone.
sulfuric acid in dry acetone. We observed that the addition of molecular
sieve increased the overall yield (37% over two steps, Sch. 2). Lactone 1
was also persilylated[20] or peracetylated[38] using standard methods, to give,
respectively, the protected galactonolactones 3 and 4 in 55% and 62% over two
steps (Sch. 2).
Scheme 3: Synthesis of D-galactono-1,4-lactone.
With peracetate 4 in hand, we addressed the possibility to selectively hy-
drolyze the four acetates without hydrolyzing the lactone. To do so, we treated
compound 4 with acetyl chloride in methanol[39] to provide methyl ester 6. Af-
ter acidic hydrolysis, lactone 1 was formed in very high yield (97%). Following
this pathway, D-galactono-1,4-lactone 1 could be prepared from D-galactose
in 60%, with one intermediate silica gel chromatography purification (Sch. 3),
this time with satisfactory analytical data.
Galactofuranosides 7 and 5 are key intermediates for the synthesis of
UDP-Galf, the substrate of important enzymes such as UGM and galactofura-
nosyltransferases.[6,17] Therefore, we also developed a novel procedure for the

V. Lemau de Talance´ et al.
610
selective reduction of the lactone into lactol 7. The classical procedure relies on
a disiamyl borane reduction, using an excess of reducing agent overnight.[17,40]
Due to impurities in the commercially available borane and to the large excess
required for the completion of this reduction, the purification is tedious and
the overall procedure is unsatisfactory. We thus developed a novel procedure
using K-selectride in place of disiamyl borane that leads to the same lactol 7
more efficiently and in a shorter time (Sch. 4). The direct one-pot acetylation
gave known peracetyl-D-galactofuranose 5 in 86%.
Scheme 4: Synthesis of peracetyl-D-galactofuranose.
CONCLUSION
A new synthesis of D-galactono-1,4-lactone was described, starting from cheap
and easily available reagents. Three key galactofuranose derivatives were ob-
tained in two steps on multigram scale with only one purification step. A mild
deacetylation methodology afforded pure D-galactono-1,4-lactone and a new
method for the reduction of the peracetyl D-galactono-1,4-lactone was devel-
oped, giving peracetyl-D-galactofuranose in good yield.
EXPERIMENTAL
All chemicals was purchased in Aldrich Chemicals Co., Acros Chemicals Co.,
or Alfa Aesar Chemicals Co. and used as purchased. Methanol was distilled
over magnesium turnings, THF over sodium/benzophenone and acetone over
MgSO4. All reactions were monitored by thin-layer chromatography (TLC) car-
ried out on Merck aluminum roll silica gel 60-F254 using UV light and a
1
molybdate-sulfuric acid solution as revelator. H and 13C NMR spectra were
1
recorded on a JEOL (JNM EX-400). All compounds were characterized by H
1
1
and 13C NMR as well as by H-1H and H-13C correlation experiment when
necessary. The following abbreviations were used to describe the multiplici-
ties: s = singlet, d = doublet, t = triplet, m = multiplet, br = broad, and br s
= broad singlet. The numbering of the protons and carbons is analogous to the
proton numbers resulting from the name of the compound. Aromatic, benzyl,
acetyl, and methyl (carbons and protons) are respectively labeled with “arom,”
“Bn,” “Ac,” and “Me” subscript; quaternary carbons are indicated with a “q”
subscript. Chemical shifts (δ) are reported in ppm and referenced indirectly to

Synthesis of D-Galactono-1,4-Lactone
611
TMS via the solvent (or residual solvent) signals. Merck silica gel (60 mesh,
particle size 0.040–0.063 mm) was employed for flash column chromatography
using technical solvent distilled prior to use as eluting systems.
D-galactono-1,4-lactone (1)
D-galactose (20 g, 111 mmol, 1.0 equiv.) and sodium bicarbonate (18.6 g,
222 mmol, 2.0 equiv.) were dissolved in water (100 mL). Bromine (6 mL,
116.6 mmol, 1.05 equiv.) was slowly added dropwise at 0◦C, and the resulting
solution was stirred 3 d at rt. Sodium bisulfite (580 mg, 11 mmol, 0.1 equiv.)
was added to quench the remaining bromine. After 10 min, the solution was
concentrated and dried in vacuo. The remaining solid was extracted by ab-
solute ethanol (3 × 200 mL) under vigorous stirring or sonication, followed
by filtration on Celite. The remaining ethanolic phases were concentrated and
dried. The remaining solid was hydrolyzed by acidic water (3 × 100 mL, 0.4 mL
of concentrated HCl per 100 mL) during 30 min, concentrated, and dried under
oil pump vacuum, to give 1 as a solid (18.6 g) that was used such as for further
derivatizations. The analytical data were identical to the data of the commer-
cial compound. 1H NMR (400 MHz, D2O): δ = 4.50 (m, 1H; H-2), 4.27–4.19 (m,
2H; H-3 H-4), 3.83–3.78 (m, 1H; H-5), 3.62–3.56 (m, 2H; H-6). 13C NMR (101
MHz, D2O): δ = 176.0 (C-1), 80.0 (C-4), 73.7 (C-2), 72.8 (C-3), 68.9 (C-5), 62.0
(C-6).
5,6-O-isopropylidene-D-galactono-1,4-lactone (2)
˚
D-galactono-1,4-lactone 1 (18.6 g) and activated 3A molecular sieve (8.4 g)
were dissolved under argon in dry acetone (740 mL); 0.2 mL of concentrated
sulfuric acid were added, and the solution was stirred 1 h at rt. The so-
lution was neutralized by sodium biocarbonate (20 g) and stirred 30 min,
then filtrated on Celite and concentrated. The residue was purified by flash
chromatography (cyclohexane/ethyl acetate 4:6) to give the expected product
(9.0 g, 37% over two steps). The analytical data were identical to the literature
data.[16,37] 1H NMR (400 MHz, CDCl3): δ = 4.63 (br s, 2H; 2 OH), 4.53 (d, J2-3
=
8.3 Hz, 1H; H-2), 4.35 (m, 2H; H-3, H-5), 4.21 (dd, J = 7.6 Hz, J = 3.9 Hz, 1H;
H-4), 4.14 (ABX, J6a-6b = 8.5 Hz, J6a-5 = 6.9 Hz, 1H; H-6a), 4.01 (ABX, J6a-6b
= 8.7 Hz, J6b-5 = 6.4 Hz, 1H; H-6b), 1.41, 1.37 (2 s, 6H; 2 CH3). 13C NMR (100
MHz, CDCl3): δ = 174.6 (C-1), 110.4 (O-C-O), 79.8 (C-4), 74.6, 74.2, 74.1 (C-2,
C-3, C-5), 65.0 (C-6), 26.0, 25.3 (2 CH3).
2,3,5,6-Tetra-O-tert-butyldimethylsilyl-D-galactono-
1,4-lactone (3)
D-galactono-1,4-lactone 1 (24.8 mmol) was dissolved in dry DMF (65.0 mL).
Imidazole (10.1 g, 148 mmol, 6.0 equiv.) and tert-butyldimethylsilyl chloride

V. Lemau de Talance´ et al.
612
(19.74 g, 131 mmol, 5.3 equiv.) were added under argon. The resulting so-
lution was then heated at 70◦C overnight, and diluted with diethylether
(200 mL) and water (20 mL). The organic layer was washed with brine,
dried over MgSO4, filtrated, and concentrated. The residue was purified
by flash chromatography (cyclohexane/ethyl acetate 40:1) to afford the ex-
pected compound (8.6 g, 55%). The analytical data were comparable to
the data of the literature.[20] [α]D –11.4 (c 1.0, CHCl3). m.p. 49–50◦C.
23
1H NMR (400 MHz, CDCl3): δ = 4.45 (t, J2-3 = J3-4 = 6.1 Hz, 1H; H-
3), 4.38 (d, J2-3 = 6.1 Hz, 1H; H-2), 4.35 (dd, J4-3 = 6.1 Hz, J4-5
=
1.7 Hz, 1H; H-4), 3.85 (ddd, J5-4 = 1.7 Hz, J5-6b = 5.8 Hz, J5-6a = 7.7 Hz, 1H;
H-5), 3.70 (ABX, J6a-6b = 9.7 Hz, J6a-5 = 7.7 Hz, 1H; H-6a), 3.66 (ABX, J6b-6a
= 9.7 Hz, J6b-5 = 5.8 Hz, 1H; H-6b), 0.95 (s, 9H; Si-tBu), 0.92 (s, 9H; Si-tBu),
0.91 (s, 9H; Si-tBu), 0.90 (s, 9H; Si-tBu), 0.23 (s, 3H; Si-Me), 0.18 (s, 3H; Si-
Me), 0.16 (s, 3H; Si-Me), 0.15 (s, 3H; Si-Me), 0.14 (s, 3H; Si-Me), 0.11 (s, 3H;
Si-Me), 0.09 (s, 6H; Si-Me). 13C NMR (100 MHz, CDCl3) : δ = 173.5 (C-1), 81.5
(C-4), 76.9 (C-2), 75.6 (C-3), 71.5 (C-5), 63.0 (C-6), 25.8, 25.8, 25.7, 25.6 (4 Si-
C(CH3)3), 18.2, 18.2, 18.1, 17.8 (4 Si-C(CH3)3), –3.4, –4.1, –4.2, –4.3, –4.7, –4.9,
–5.4, –5.5 (8 Si-Me). MS (DIC-NH3): m/z 652 [M + NH4]+. Elemental analysis
for C30H66O6Si4: calcd(%): C 56.73 H 10.47. found: C 56.87 H 10.58.
2,3,5,6-Tetra-O-acetyl-D-galactono-1,4-lactone (4)
D-galactono-1,4-lactone (11.1 mmol) was dissolved under argon in pyri-
dine (20 mL) and the mixture was sonicated 2 min. Acetic anhydride (65 mL,
69.0 mmol, 6.15 equiv.) was then added at 0◦C, and the resulting solution was
stirred 6 h at rt and dropped on ice (40 g). Ethyl acetate (50 mL) was added.
The organic layer was washed with HCl 10% solution (2 × 50 mL) and brine
(50 mL), dried on MgSO4, and concentrated in vacuo. The residue was purified
by flash chromatography (cyclohexane/ethyl acetate 1:1) to give the expected
product as a white solid (2.37 g, 62% over two steps). The analytical data were
comparable to the data of the literature.[38] [α]D –12.1 (c 1.0, CHCl3). m.p.
20
1
70◦C. H NMR (400 MHz, CDCl3): δ = 5.60 (d, J2-3 = 7.0 Hz, 1H; H-2), 5.42
(t, J2-3 = J3-4 = 7.0 Hz, 1H; H-3), 5.32 (ddd, J5-6a = 6.4 Hz, J5-6b = 5.5 Hz,
J5-4 = 2.8 Hz, 1H; H-5), 4.59 (dd, J4-3 = 6.8 Hz, J4-5 = 2.8 Hz, 1H; H-4), 4.32
(ABX, J6b-6a = 11.9 Hz, J6b-5 = 5.5 Hz, 1H; H-6b), 4.23 (ABX, J6a-6b = 11.9 Hz,
J6a-5 = 6.4 Hz, 1H; H-6a), 2.18 (s, 3H; Ac), 2.15 (s, 3H; Ac), 2.11 (s, 3H; Ac), 2.07
(s, 3H; Ac). 13C NMR (101 MHz, CDCl3): δ = 170.3 (C=O), 169.7 (C=O), 169.6
(C=O), 169.3 (C=O), 168.0 (C-1), 77.3 (C-4), 72.2 (C-3), 71.9 (C-2), 68.2 (C-5),
61.6 (C-6), 20.6, 20.5, 20.3 (4 Ac). MS (ESI-Na): m/z 369 [M + Na]+. HRMS for
C14H18O10Na: calcd: 369.0798. found: 369.0812.
D-galactono-1,4-lactone (1) from 4
The 2,3,5,6-tetra-O-acetyl-D-galactono-1,4-lactone 4 (2.37 g, 6.84 mmol,
1.0 equiv.) was dissolved under argon in dry methanol (150 mL) at 0◦C. Acetyl

Synthesis of D-Galactono-1,4-Lactone
613
chloride (4.9 mL, 68.4 mmol, 10.0 equiv.) was added dropwise and the solu-
tion was stirred at 0◦C during 8 h and 18 h at 4◦C. The solution was then
concentrated, hydrolyzed by acidic water (2 × 50 mL, 0.4 mL of concentrated
HCl per 100 mL) during 30 min, concentrated, and dried in vacuo to afford
D-galactono-1,4-lactone 1 (1.19 g, 97%).
1,2,3,5,6-Penta-O-acetyl-D-galactofuranose (5)
The 2,3,5,6-tetra-O-acetyl-D-galactono-1,4-lactone 4 (400 mg, 1.16 mmol,
1.0 equiv.) was dissolved in dry THF (2.5 mL) under argon. K-selectride (1M
in THF, 1.16 mL, 1.16 mmol, 1.0 equiv.) was slowly added at –78◦C and the
mixture was stirred during 1 h. After a first addition of K-selectride (0.25 mL,
0.25 mmol, 0.22 equiv.), the mixture was stirred during 45 min, followed by
a second addition of K-selectride (0.25 mL, 0.25 mmol, 0.22 equiv.). Forty-five
minutes after this addition, DMAP (565 mg, 4.62 mmol, 4 equiv.) and acetyl
chloride (0.33 mL, 4.62 mmol, 4 equiv.) were added. The resulting solution was
warmed to 0◦C, maintained at this temperature during 45 min, and stirred
overnight at –18◦C. The excess of acetyl chloride was neutralized with a sat-
urated solution of ammonium chloride (10 mL) at 0◦C. After extraction with
dichloromethane, the organic layer was dried over MgSO4, filtrated, and con-
centrated under vacuo. The residue was purified by silica gel chromatography
(cyclohexane/ethyl acetate 3:1) to afford the expected compound (388 mg, 86%,
α/β: 1.1:1). The analytical data were comparable to those of the literature.[13]
1H NMR (400 MHz, CDCl3): δ = 6.33 (d, J1-2 = 4.8 Hz, 1H; H-1α), 6.19 (s, 1H;
H-1β), 5.55 (t, J2-3 = J3-4 = 6.6 Hz, 1H; H-3α), 5.38–5.25 (m, 3H; H-2α, H-5α, H-
5β), 5.19 (d, J2-3 = 2.0 Hz, 1H; H-2β), 5.09 (dd, J3-4 = 5.4 Hz, J3-2 = 2.0 Hz, 1H;
H-3β), 4.38–4.13 (m, 6H; H-4α, H-4β, H-6aα, H-6aβ, H-6bα,H-6bβ), 2.14–2.10 (m,
18H; 3 Acα, 3 Acβ), 2.09 (s, 3H; Acα), 2.08 (s, 3H; Acα), 2.08 (s, 6H; 2 Acβ). 13C
NMR (101 MHz, CDCl3): δ = 170.5 (C=O Acβ), 170.4 (C=O Acα), 170.0 (C=O
Acβ), 169.9 (C=Oα), 169.8 (C=Oα), 169.8 (C=Oα), 169.7 (C=Oβ), 169.4 (C=Oβ),
169.3 (C=Oα), 169.0 (C=Oβ), 99.1 (C-1β), 93.0 (C-1α), 82.1 (C-4β), 80.6 (C-2β),
79.0 (C-4α), 76.3 (C-3β), 75.3 (C-2α), 73.3 (C-3α), 70.3 (C-5α), 69.2 (C-5β), 62.5
(C-6β), 62.1 (C-6α), 21.0, 20.9, 20.8, 20.8, 20.7, 20.7, 20.6, 20.5 (5 Acα, 5 Acβ).
ACKNOWLEDGEMENT
This work was funded by FNRS (“Mandat d’Impulsion Scientifique” F.4502.09,
FRFC grant 2.4.625.08.F, “Cre´dit au chercheur” 1.5.167.10 and F.R.I.A., Fonds
pour la Formation a` la Recherche dans l’Industrie et dans l’Agriculture) and
by the Acade´mie Louvain (A.R.C. 08/13-012).

V. Lemau de Talance´ et al.
614
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