Synthesis of 2(R),3-dihydroxypropyl and 2(R),3(R)-dihydroxybutyl β-d-fructopyranosides and some derivatives

Article abstract of DOI:10.1016/j.carres.2006.02.005

The synthesis of 2(R),3-dihydroxypropyl and 2(R),3(R)-dihydroxybutyl β-d-fructopyranosides, and some derivatives, employing Sharpless-type catalytic asymmetric dihydroxylation procedures is described. Some aspects of the reactions, including stereoselecti

Full text of DOI:10.1016/j.carres.2006.02.005

Carbohydrate Research 341 (2006) 846–854
Synthesis of 2(R),3-dihydroxypropyl and 2(R),3(R)-dihydroxybutyl
b-D-fructopyranosides and some derivatives
Fortunatus Sung’hwa,ꢀ Axel Strik, Henk Regeling,* Binne Zwanenburg
and Gordon J. F. Chittenden
Department of Organic Chemistry, IMM Center, Radboud University Nijmegen, Toernooiveld 1,
NL-6525 ED Nijmegen, The Netherlands
Received 9 September 2005; received in revised form 24 January 2006; accepted 9 February 2006
Available online 10 March 2006
Abstract—The synthesis of 2(R),3-dihydroxypropyl and 2(R),3(R)-dihydroxybutyl b-D-fructopyranosides, and some derivatives,
employing Sharpless-type catalytic asymmetric dihydroxylation procedures is described. Some aspects of the reactions, including
stereoselectivities and chemical evidence for the assigned stereochemistry of the main products are reported.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Alkenyl fructosides; Dihydroxyalkyl fructosides; Asymmetric dihydroxylations; Fructosyl glycolipids
1. Introduction
glyceryl-fructosides during the enzymatic synthesis of
some levans from sucrose has been implied, but never
substantiated.8 Treatment of D-fructose with glycerol
in the presence of mesoporous catalysts yielded9 compli-
cated mixtures, which were not separated or investi-
gated. The enzymatic synthesis of some D-fructosyl
glycerols by reaction of sucrose with glycerol in the pres-
ence of levan sucrases from Bacillus circulans and Bacil-
lus subtilis has been reported.10 Concurrent hydrolysis of
the products and levan synthesis by the enzymes gave
low yield. There was only a slight preference of reaction
on glycerol at either of the two primary hydroxyl groups
over the secondary group. The authors refer consistently
to their products as pyranose derivatives but present
structures in the furanoid form. The physical data pre-
sented support the latter.
Glycosides of glycerol are important basic units of
glyceroglycolipids. These are widely distributed in nat-
ure, and have been isolated from many sources including
plants, animal tissue, bacteria and marine organisms.1–4
The glycerol hydroxyl groups are usually esterified or
etherified by a variety of long-chain fatty acids or alkyl
residues. They play important roles in cell surface recog-
nition–interaction and the maintenance of membrane
structure and fluidity.2 There has been a recent resur-
gence of interest in these compounds, particularly those
in which a sugar unit is b-linked to a primary position of
glycerol, because of the newly discovered interesting bio-
logical properties including inter alia, anti-tumour and
anti-inflammatory activities.5–7
No lipid structures containing D-fructose have been
reported despite it being the second most abundant nat-
ural monosaccharide. The intermediate formation of
We now report the synthesis of 2(R),3-dihydroxy-
propyl b-D-fructopyranoside (1-O-fructopyranosyl-sn-
glycerol, 1) and some related compounds. Long-chain
alkyl esters of compound 1 are also described.
*
Corresponding author at present address: MercaChem BV, PO Box
31070, 6503 CB Nijmegen, The Netherlands. Tel.: +31 (0)243
528832; fax: +31 (0)243 653881; e-mail: regeling@mercachem.com
2. Results and discussion
ꢀ Present address: Department of Chemistry, University of Dar es
Salaam, PO Box 35061, Dar es Salaam, Tanzania.
The synthesis of specifically defined fructosides is diffi-
cult.11 Normal acid catalyzed glycosidation tends to lead
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.02.005

F. Sung’hwa et al. / Carbohydrate Research 341 (2006) 846–854
847
to complex anomeric mixtures of pyranosides and fur-
anosides and dehydration–decomposition products aris-
ing from elimination. Koenigs–Knorr procedures using
D-fructose are also difficult. The catalytic asymmetric
dihydroxylation (AD)12,13 of allyl b-D-fructopyran-
oside14 (2) was investigated. There are few examples of
the use of the Sharpless AD protocol for the synthesis
of dihydroxyalkyl glycosides.15–18 The synthesis of
several glycosyl glycerols was described recently.19
Acetylated allyl glycosides were converted into 1-O-(glyco-
pyranosyl)-rac-glycerols by epoxidation with m-chloro-
perbenzoic acid, followed by opening of the resultant
oxiranes with BF3ÆEt2O. There was little or no diastereo-
selectivity indicated.
Benzylation of 2 gave the crystalline tetra-O-benzyl
derivative 3. This was used as the basic substrate for
the various AD reactions. The benzyl group was chosen
as a protecting function for its known stability and the
eventual ease of removal by catalytic hydrogenolysis.
This was an important factor for the projected synthesis
of some long-chain acyl esters of the glyceryl fructosides
to be anticipated from the oxidations. A recent report18
also suggested that mutual p–p stacking of aromatic
nuclei with some AD ligands can lead to enhanced
facial diastereoselectivity. The use of O-acetyl protecting
groups on some polyhydroxy substrates in AD reactions
has not always resulted in good stereoselectivities.15–17
Compound 3 was initially subjected to catalytic osmy-
lation using the phthalazine-based chiral ligands
(DHQD)2PHAL and (DHQ)2PHAL at 22 ꢁC. These
two ligands are components of the commercially avail-
able AD-mix a, and AD-mix b, respectively. The pyrim-
idine-based ligands (DHQD)2PYR and (DHQ)2Py were
also included in this study. The yields of crystalline
material, mixtures of diastereoisomers, obtained after
column chromatography and the respective degrees of
stereoselectivity as expressed by the de values are sum-
marized in Table 1. The de values were determined by
analysis (GLC) of per-O-acetylated samples obtained
from the isolated reaction products by sequential
de-O-benzylation (catalytic hydrogenolysis; H2/Pd–C,
10%), followed by acetylation in the usual manner.
The use of pyrimidine-based ligands led to consistent,
and relatively high de values. A previous observation sug-
gests that the dihydroquinidine ligand (DHQD)2-PYR
was superior in most AD reactions of terminal olefins.20
The importance of chiral ligand structures in AD reac-
tions has been discussed.16
When the above reactions were conducted at 0 ꢁC
no improvements in yields or de values were noted.
Previous studies on other AD-type reactions involving
alkenyl glycosides conducted at 0 ꢁC noted improved
yields and higher selectivities.15–18
Recrystallization of the products obtained from the
AD reactions of compound 3 appeared to give the same
pure diastereomer 1, mp 101–103 ꢁC, [a]D ꢀ59, in each
case.
The stereochemistry at position C-2 of the generated
dihydroxypropyl unit was established in the following
manner. Samples of the products obtained using
(DHQD)2PHAL and (DHQ)2PYR, as representative
ligands, were benzylated in the usual manner and these
products were subjected to acid hydrolysis. Column
chromatography of the resultant products gave the
known21 2(R)-1,2-dibenzyloxypropan-1-ol (6) in each
case. Further elution gave the tetra-O-benzyl-D-
fructoses 5, as anomeric mixtures, which were not
investigated.
These results established the stereochemistry at C-2 as
the same in each case. It may have been expected that
the use of ligands based on dihydroquinidine and
dihydroquinine could have given rise to different config-
urations of the hydroxyl group at C-2 in each case.
It seemed that the relatively large O-benzyl group
attached to the C-1 position of the b-D-fructopyranosyl
unit has a profound effect on the approach of the effec-
tive reagent complexes. Previous studies15,16,18 have
indicated that it is not always possible to achieve
respectable diastereoselectivities during the dihydroxyl-
ation of alkenyl glycosides in the presence of chiral
auxiliaries. A number of other factors play a significant
role. These include the length of the alkenyl chain, the
position of the unsaturation, the nature and size of the
protecting functions, the anomeric configuration and
the preferred conformation of the sugar ring. These
intramolecular factors seem to outweigh other consider-
ations, which can determine diastereofacial preferences
in the chiral auxiliary catalyzed dihydroxylation
processes.
Next we studied the preparation of some long-chain
di-O-acyl derivatives of the glycerol compound 1. Treat-
ment of 1 in pyridine–dichloromethane solution at 0 ꢁC
with dodecanoyl, tetradecanoyl and hexadecanoyl chlo-
ride (3 equiv) in the usual manner yielded the esters 7–9,
respectively. The products, which were colourless oils,
required purification by column chromatography (75–
91% yield). Subsequent removal of the O-benzyl protect-
ing groups from these products by catalytic hydrogeno-
lysis (H2/Pd–C, 10%) gave the crystalline glyceryl
derivatives 10–12. The slightly modest yields (50–
58%) of these compounds could be attributed to the
Table 1. Asymmetric dihydroxylation of compound 3 at 22 ꢁC
Chiral ligand
Chemical yield (%)
dea (%)
(DHQD)2PHAL
(DHQ)2PHAL
(DHQD)2PYR
(DHQ)2PYR
97.5
70
82
67
27
56
76
88
(DHQD)2AQN
(DHQ)2AQN
97.5
90
63.5
27
a Determined by GLC—see Experimental section.

848
F. Sung’hwa et al. / Carbohydrate Research 341 (2006) 846–854
Catalytic asymmetric dihydroxylation of 13 was car-
O
OR1
O
O
O
RO
R2O
ried out as described earlier, but using only two ligands,
namely, (DHQD)2PHAL and (DHQ)2PHAL. The reac-
tions were performed at room temperature, and in the
presence of methanesulfonamide, which has been
claimed23–25 to enhance the rate of hydrolysis of inter-
mediate osmate esters. In each case only one main prod-
uct was obtained in 82% and 88% yield, respectively.
Analysis (GLC) on samples subjected to a sequential
hydrogenolysis/acetylation sequence (vide supra)
showed high de values of 97% and 96%, respectively.
The recrystallized products from each of the two
reactions appeared to be the same compound 16, and
implying that the expected alteration of product stereo-
chemistry using the AD-a and AD-b ligands was not
observed. Intramolecular stereocontrol by the fructosyl
unit appears to prevail over the molecular control by
the chiral catalyst, despite the double bond being situ-
ated between two secondary carbon atoms in the middle
of the aglycon. This situation could have imposed great-
er selectivity in the chiral auxiliary catalyzed reaction
due to increased diastereofacial preference.
OR1
OR2
R2O
RO
OR
OR2
OR
1 R1 = H, R2 = Bn
4 R1 = R2 = Bn
2 R = H
3 R = Bn
7 R1 = C11H23CO; R2= Bn
8 R1 = C13H27CO; R2= Bn
9 R1 = C15H31CO; R2= Bn
10 R1 = C11H23CO; R2= H
11 R1 = C13H27CO; R2= H
12 R1 = C15H31CO; R2= H
O
OH
BnO
HO
OBn
CH2OBn
BnO
OBn
OBn
5
6
Scheme 1.
The absolute configuration of the 2,3-diol group in
compound 16 was determined as described for com-
pound 1. Benzylation of 16 under basic conditions
yielded the per-O-benzyl derivative 17, which was
hydrolyzed (TFA–H2O, 9:1) to give the 1-deoxy-D-thre-
itol compound 18. Catalytic hydrogenolysis (Pd–C,
10%) of 18 followed by reaction of the resultant product
with p-nitrobenzoyl chloride in pyridine gave the
known26–28 tris-p-nitrobenzoate 19, which established
the 2(R),3(R) configuration for the diol group at C-2
and C-3.
difficulties encountered in purifying the crude products
(Scheme 1).
This study was extended to the preparation and
dihydroxylation of the but-2-enyl derivative 13. The nec-
essary starting compound 14 had not been described
previously. Treatment of D-fructose with but-2-en-1-ol
(crotyl alcohol; cis/trans, 1:19) in the presence of a cat-
alytic quantity of acetyl chloride at room temperature
for 48 h gave crystalline 14. The reaction mixture re-
mained heterogeneous throughout the reaction period.
Catalytic hydrogenation14 of a portion of the product
gave the known butyl22 compound 15. Benzylation of
the fructoside 14 yielded the tetra-O-benzyl derivative
13 (88.5%), as an oil (Scheme 2).
3. Experimental
General—Optical rotations were determined with a
Perkin–Elmer automatic polarimeter, model 241 MC,
at 20 ꢁC, on 1% solutions in the solvents indicated. Col-
umn chromatography was performed using silica gel
60 (E. Merck) using the eluents indicated. Thin layer
chromatography (TLC) on pre-coated plates of silica
gel GF254 (E. Merck) was conducted in the solvent mix-
tures indicated. Compounds were detected by spraying
with 3% H2SO4 in EtOH, followed by heating at
140 ꢁC. Gas-liquid chromatography (GLC) was per-
formed on a Hewlett–Packard 5890 gas chromatograph
using a fused capillary column (25 m) coated with HP-1,
cross-linked methyl silicone (gum phase) operating at
100 ! 200 ꢁC (t = 0 min, isothermal, t = 5 min,
O
O
RO
O
O
HO
RO
OR
HO
OH
OR
OH
15
13 R = Bn
14 R = H
OR1
OR1
O
O
R2O
OR1
OR2
R3O
R2O
OR2
OR2
18 R1 = R2 = Bn, R3 = H
5 ꢁC minꢀ1) with nitrogen as carrier gas at 2 mL minꢀ1
.
16 R1 = H, R2 = Bn
17 R1 = R2 = Bn
1H NMR spectra were recorded on Bruker AC 100
(100 MHz, FT), AC 300 (300 MHz) or AC (400 MHz)
spectrometers on solutions in CDCl3 (internal standard
Me4Si) or D2O (internal standard HDO). 13C NMR
19 R1 = R2 = R3 =
NO2
O
Scheme 2.

F. Sung’hwa et al. / Carbohydrate Research 341 (2006) 846–854
849
spectra were recorded on a Bruker AC 100 (100 MHz),
AC 300 (300 MHz) or AM 400 spectrometers operating
at 25.0, 75.0 and 100.6 MHz, respectively, in CDCl3
(internal Me4Si) or D2O (external 1,4-dioxane,
76.8 ppm). Mass spectra were recorded using a double
focussing VG 7070E spectrometer in the mode indi-
cated. (DHQD)2PHAL, (DHQ)2PHAL, (DHQD)2PYR,
(DHQ)2PYR, (DHQD)2AQN and (DHQ)2AQN were
purchased from Sigma–Aldrich and were used as
supplied.
ether (100 mL) and water (30 mL). The aqueous layer
was extracted with ether (2 · 30 mL) and the combined
organic layers washed with saturated aqueous NaCl
(40 mL), dried (MgSO4) and concentrated in vacuo.
Column chromatography (hexane–EtOAc, 1:3) of the
resultant material gave white crystals (4.85 g, 90.5%)
as mixtures of diastereoisomers. Pure compound 1
(2.71–3.25 g, 50–60%) was obtained by recrystallization
of the material (isopropylether), mp 101–102 ꢁC [a]D
ꢀ59.3 (CHCl3); MS (CI-CH4) m/z 615 (M+H)+
523 (M+HꢀHOCH2ꢀCH(OH)CH2OH)+. 1H NMR
(CDCl3, 400 MHz): d 7.39–7.17 (m 20H, aromatic H),
4.87, 4.61 (2d, each 1H, J 10.8 Hz, benzylic H), 4.73–
4.69 (2d, each 1H, J 12.6 Hz, benzylic H) 4.64–4.62
(m, 2H, benzylic H), 4.58, 4.42 (2d, each 1H, J 11.9
Hz, benzylic H), 4.33 (d, 1H, J 10.0 Hz, H-3), 3.90
(dd, 1H, J3,4–J4,5 3.0 Hz, H-4), 3.85 (dd, 1H, J5,6eq 1.8,
J6ax,6eq ꢀ12.4 Hz, H-6eq), 3.73 (d, 1H, J ꢀ10.2 Hz, H-
1a), 3.72 (m, 1H, H-5), 3.55 (dd, 1H, J5,6ax 1.7, J6ax,6eq
ꢀ12.4 Hz, H-6ax), 3.52 (m, 1H, H-20), 3.44–3.41 (m,
3.1. Allyl 1,3,4,5-tetra-O-benzyl b-D-fructopyranoside (3)
A cooled (0 ꢁC), stirred mixture of allyl b-D-fructo-
pyranoside (2)14 (7.41 g, 33.7 mmol) in Me2SO (30 mL)
containing powdered KOH (7.54 g, 135 mmol) was
treated with benzyl chloride (15.5 mL, 135 mmol), and
set aside at room temperature for 12 h. The mixture was
treated with ether (100 mL) and water (40 mL), the sep-
arated aqueous layers extracted with ether (50 mL), the
combined organic layers washed with saturated aqueous
NaCl, dried (MgSO4) and concentrated in vacuo. Col-
umn chromatography (hexane–EtOAc, 3:1) of the crude
material gave 3 (15.5 g, 79.5%) a pure colourless oil, [a]D
2H, H-10a, 10b), 3.42 (d, 1H, J3 a;2 6.1 Hz, H-30a), 3.39
0
(d, 1H, J3 b;2 6.1 Hz, H-30b), 2.97 (br s, 1H, OH), 2.26
0
(br s, 1H, OH). 13C NMR (CDCl3, 75 MHz): d 138.34,
138.27, 137.66, 128.21, 128.12, 128.03, 127.77, 127.63,
127.53, 127.43 (aromatic C), 101.04 (C-2), 78.58 (C-3),
76.49 (C-4), 75.60, 73.53 (benzylic-C), 73.24 (C-5),
71.94, 71.12 (benzylic-C), 70.09 (C-20, C03), 63.69 (C-1,
C-10), 61.03 (C-6) ppm. Anal. Calcd for C37H42O8: C,
72.29; H, 6.89. Found: C, 72.45; H, 6.87.
1
ꢀ49.6 (CHCl3). H NMR (CDCl3, 400 MHz): d 7.40–
7.19 (m, 20H, aromatic H), 5.93–5.84 (m, lH, H-20),
5.23(dd, 1H, J2 a;3 a 15.8, J3 a;3 b 1.3 Hz, H-30a), 5.00
0
0
0
0
0
0
0
0
(dd, 1H, J2b 3 b, 1.1, J3a0;3b 1.3 Hz H-3 b), 4.93, 4.62 (2d,
each 1H, J 11.2 Hz, benzylic H), 4.76, 4.71 (2d, each
1H, J 12.6 Hz, benzylic H), 4.68, 4.45 (2d, each 1H, J
11.9 Hz, benzylic H), 4.62–4.56 (m, each 1H, benzylic-
H), 4.39 (d, 1H, H-3), 4.14–4.12 (m, 2H, H-10a, H-
10b), 4.10 (m, 1H, H-5), 4.01 (dd, 1H, J3,4 = J4,5
3.1 Hz, H-4), 3.87 (dd, 1H, J5,6eq 1.4, J6ax,6eq
ꢀ12.4 Hz, H-6eq), 3.84, 3.77 (2d, each 1H, J ꢀ10.1
Hz, H-1a, H-1b), 3.55 (dd, 1H, J5,6ax 1.4, J6ax,6eq
ꢀ12.4 Hz, H-6ax) ppm. 13C NMR (CDCl3, 75 MHz):
d 138.84, 138.62, 138.74, 137.99, 128.20, 128.07,
128.02, 127.67, 127.57, 127.37, 127.22 (aromatic C),
135.12 (OCH2CH–CH2), 115.88 (OCH2OH–CH2),
101.83 (C-2), 78.73 (C-3), 76.17 (C-4), 75.43 (benzylic-
C), 73.62 (C-5), 73.43, 72.17, 71.09 (benzylic-C), 70.15
(C-1), 62.20 (C-10) and 61.14 (C-6) ppm.
3.3. Determination of degree of enantioselectivity (de)
values
Samples (25–30 mg) of products arising from various AD
reactions (Table 1) dissolved in methanol (25 mL) were
hydrogenated (1 atm) in the presence of palladized char-
coal (10%, 8 mg) for 18–20 h. The mixtures were filtered,
the inorganic material washed with methanol (2 · 10 mL)
and the combined filtrate and washings concentrated in
vacuo. The resultant residues were treated with Ac2O
(1.5 mL) and pyridine (4 mL) in the usual manner and
the products obtained after processing were dissolved in
CH2Cl2 and used directly for analysis (GLC).
3.2. 2(R),3-Dihydroxypropyl 10,30,40,50tetra-O-benzyl-b-
D-fructopyranoside (1)
3.4. 2(R)3-Dibenzyloxypropyl 10304050-tetra-O-benzyl-b-
D-fructopyranoside (4)
By Sharpless-type asymmetric dihydroxylation (AD) of
compound 2—General procedure—A stirred solution of
potassium(IV)osmateÆdihydrate (12.22 mg), K2CO3
(3.66 g), K3Fe(CN)6 (8.65 g) and the appropriate chiral
ligand (8.5 · 10ꢀ5 mol; see Table 1) in H2O (25 mL)
was added to a rapidly stirred solution of compound 2
(5.06 g, 8.75 mmol) in 2-methylpropan-2-ol (30 mL)
and then set aside for ca. 12 h. The mixture was treated
with Na2SO3 (15 g) stirred for 1 h and then treated with
A stirred, cooled (0 ꢁC) solution of compound 1
(1.603 g, 2.6 mmol) in Me2SO (10 mL) was treated
sequentially with powdered KOH (437 mg, 7.8 mmol,
3 equiv) and benzyl chloride (0.8 mL, 7.8 mmol, 3 equiv)
and set aside at room temperature for 18 h. The mixture
was treated with water (20 mL) and ether (70 mL), the
separated aqueous layer was extracted with ether
(2 · 15 mL) and the combined organic layers washed
with water, dried (Na2SO4) and concentrated in vacuo.

850
F. Sung’hwa et al. / Carbohydrate Research 341 (2006) 846–854
Column chromatography (3:1; n-hexane–EtOAc) gave
compound 4 (1.83 g, 77%) as an oil [a]D ꢀ57.4 (CHCl3).
1H NMR (CDCl3, 100 MHz): d 7.44–7.21 (m, 30H, aro-
matic H), 4.98–4.61 (d, 1H, J 11.4 Hz, benzylic H), 4.77,
4.71 (2d, each 1H, J 12.8 Hz, benzylic H), 4.68–4.57 (m,
8H, benzylic H), 4.44 (d, 1H, J 11.9 Hz, benzylic H),
4.36 (d, 1H, J3,4 10.1 Hz, H-3), 3.93 (dd, 1H, J4,5
3.2 Hz, H-4), 3.85–3.54 (m, 9H, H-1a, H-1b, H01a,
H01b, H-20, H-30, H-5, H-6ax, H-6eq) 1.17 (d, 3H,
CH3). 13C NMR (CDCl3, 75 Hz): d 138.50, 138.35,
138.34, 137.71, 128.29, 128.17, 127.85, 127.86, 127.79,
127.68, 127.65, 127.57, 127.53 (aromatic C), 100.95 (C-
2), 78.73 (C-3), 76.65 (C-4), 75.52, 73.66 (benzylic C),
70.24 C-1, 68.50 (C-30) 64.85 (C-1), 61.24 (C-6) ppm.
with a solution of dodecanoyl chloride (0.38 mL,
1.68 mmol, 3 equiv) in dichloroethane (10 mL) and then
maintained at room temperature for a further 2 h.
The mixture was treated with ice-water (15 mL), di-
luted with more CH2Cl2 (20 mL) and the separated or-
ganic layer washed successively with 2 M aqueous
hydrochloric acid (20 mL), saturated aqueous sodium
hydrogencarbonate (20 mL), water (20 mL), dried
(Na2SO4) and concentrated in vacuo. Column chroma-
tography (hexane–ethyl acetate, 9:1) of the residue gave
7 (501 mg, 91%) as a pure colourless oil, [a]D ꢀ35
(CHCl3). 1H NMR (CDCl3, 300 MHz): d 7.40–7.19
(m, 20H, aromatic H), 5.21 (m, 1H, H-20), 4.92, 4.62
(2d, each 1H, J 11.4 Hz, benzylic-H), 4.77, 4.71 (2d, each
1H, J 12.7 Hz, benzylic-H), 4.64, 4.43 (2d, each 1H, J
11.9 Hz, benzylic-H), 4.60, 4.58 (2d, each 1H, J
11.6 Hz, benzylic-H), 4.32 (d, 1H, J 10.0 Hz, H-3),
4.10 (d, 1H, J 6.2 Hz, H-1a0), 4.0 (d, 1H, J 6.2 Hz, H-
1b0), 3.95 (dd, 1H, J3,4, J4,5 3.1 Hz, H-4), 3.88 (dd, 1H,
J5,6eq 1.6 Hz, J6ax,6eq ꢀ12.3 Hz, H-6eq), 3.84 (dd,
1H, J5,6ax 1.5 Hz, J6ax,6eq ꢀ12.3 Hz, H-6ax), 3.77 (m, 1H,
H-5), 3.75 (d, 1H, J ꢀ10.2 Hz, H-1a), 3.64 (dd, 1H,
3.5. 2(R),3-Dibenzyloxypropan-1-ol (6)
A stirred solution of compound 4 (1.75 g, 2.21 mmol) in
dioxane (41 mL) was treated with 2 M aqueous HCl
(2.48 mL), stirred for 8 days at 50 ꢁC and treated with
a saturated aqueous sodium hydrogen carbonate solu-
tion (50 mL). The mixture was extracted with ether
(3 · 50 mL), and the combined organic layers were
washed with brine (50 mL), dried (MgSO4) and concen-
trated in vacuo. Column chromatography (dichloro-
methane–methanol, 200:1) of the resultant material
gave compound 5 (511 mg, 61%); [a]D ꢀ32 (CHCl3)
(anomeric mixture) as a colourless oil. 1H NMR (CDCl3
300 MHz): d 7.41–7.10 (m, aromatic H), 4.96–4.92 (d, J
11.2 Hz), 4.80–4.76 (m), 4.73–4.67 (m), 4.63 (s), 4.59–
4.35 (m), 4.06–3.95 (m), 3.93–3.64 (m), 3.53 (d, 1H, J
9.9 Hz), 3.50 (d, 1H, J 9.9 H), 3.37 (d, 1H, J 9.7 Hz)
ppm. 13C NMR (CDCl3, 75 MHz): d 138.35, 138.08,
137.72, 137.63, 128.48, 128.38, 128.36, 128.33, 128.30,
128.14, 128.09, 127.99, 127.93, 127.85, 127.77, 127.70,
127.66, 127.58 (aromatic C), 98.06 (C-2, b-anomer),
97.38 (C-2, a-anomer), 78.87, 75.73, 75.43, 74.41,
74.32, 73.98, 73.78, 73.72, 73.41, 73.16, 72.03, 71.97,
71.62, 71.41, 71.18, 60.08, 57.28 ppm. Further elution
gave compound 6 (339 mg, 57%) as a colourless oil.
[a]D +17.9 (CHCl3); lit.20 [a]D +15.7 (CHCl3); lit.29
J3 a;2 6.5 Hz, H-30a), 3.62 (d, 1H, J ꢀ10.2 Hz, H-1b),
0
0
3.58 (d, 1H, J3 b;2 6.5, H-30b), 2.3–2.2 (m, 4H, COCH2),
1.60–1.54 (m, 4H, CH2CH2CH3), 1.25 (m, 32H, ali-
phatic H) and 0.87 (2 · t, 6H, J 6.8 Hz 2 · CH3) ppm.
13C NMR (CDCl3, 75 MHz): d 173.30, 172.93 (C@O),
139.02, 138.52, 138.43, 137.86, 128.22, 128.03, 127.67,
127.51, 127.41, 127.11 (aromatic-C), 101.65 (C-2),
78.44 (C-3) 76.99 (C-4), 74.96, 73.68 (benzylic-C),
73.54 (C-5), 72.28, 71.23 (benzylic-C), 70.00 (C-1),
69.92 (C-20), 62.44 (C-10), 61.31 (C-6), 59.86 (C-30),
34.21 (COCH2), 34.06 (COCH2), 31.86–22.64 (aliphatic
C) and 14.08 (CH3) ppm.
0
0
3.7. 2(R),3-Dihydroxypropyl 10304050-tetra-O-benzyl-b-D-
fructopyranoside 2,3-ditetradecanoate [2(R),3-(di-tetra-
decanoyloxy)propyl 10304050-tetra-O-benzyl-b-D-fructo-
pyranoside] (8)
Compound 1 (205 mg, 0.33 mmol) was treated with tet-
radecanoyl chloride (0.22 mL, 0.999 mmol, 3 equiv) as
described above to yield 8 (257 mg, 75%), [a]D ꢀ28
1
[a]D (S-enantiomer) ꢀ17.2 (CHCl3). H NMR (CDCl3,
100 MHz): d 7.36–7.24 (m, 10H, aromatic H), 4.66,
4.53 (2s, 4H, benzylic-H), 3.87–3.54 (m, 5H, aliphatic
H), 2.26 (br s, 1H, OH) ppm. 13C NMR (CDCl3,
75 MHz): d 137.61, 128.47, 127.94, 127.70, 127.69,
127.64, 127.55, 127.52 (aromatic-C), 72.35, 70.20 (benz-
ylic-C), 65.13, 63.69, 62.65 (C-1, C-2, C-3 glycerol).
(CHCl3) as
a
colourless oil. 1H NMR (CDCl3,
300 MHz): d 7.53–7.19 (m, 20H, aromatic H), 5.21 (m,
1H, H-20), 4.91, 4.61 (2d, each 1H, J 11.5 Hz, benz-
ylic-H), 4.76, 4.73 (2d, each 1H, J 12.7 Hz, benzylic-
H), 4.64, 4.43 (2d, each 1H, J 11.9 Hz, benzylic-H),
4.60, 4.58 (2d, each 1H, J 11.6 Hz, benzylic-H), 4.30
(d, 1H, J 10.0 Hz, H-3), 4.10 (d, 1H, J 6.2 Hz, 1a0),
4.00 (d, 1H, J 6.2 Hz, H-1b0), 3.94 (dd, 1H, J3,4, J4,5
3.1 Hz, H-4), 3.88 (dd, 1H, J5,6eq 1.7 Hz, J6ax,6eq
ꢀ12.3 Hz, H-6eq), 3.84 (dd, 1H, J5,6ax 1.6 Hz, J6ax,6eq
ꢀ12.3 Hz, H-6ax), 3.77 (m, 1H, H-5), 3.75 (d, 1H, J
ꢀ10.2 Hz, H-1a), 3.62 (d, 1H, J ꢀ10.2 Hz, H-1b), 3.64
3.6. 2(R),3-Dihydroxypropyl 103040-50-tetra-O-benzyl-b-
D-fructopyranoside 2,3-di-dodecanoate [2(R),3-didodeca-
noyloxypropyl 10304050-tetra-O-benzyl-b-D-fructopyran-
oside] (7)
A stirred, cooled (0 ꢁC), solution of 1 (345 mg,
0.56 mmol) in dry pyridine (5 mL) was treated gradually
(d, 1H, J3 a;2 6.5 Hz, H-30a), 3.58 (d, 1H, J3 b;2 6.5 Hz,
0
0
0
0

F. Sung’hwa et al. / Carbohydrate Research 341 (2006) 846–854
851
H-30b), 2.3–2.2 (m, 4H, COCH2), 1.62–1.53 (m, 4H,
CH2CH2CH3), 1.25 (m, 40H, aliphatic H) and 0.87
(2 · t, 6H, J 6.8 Hz, 2 · CH3) ppm. 13C NMR (CDCl3,
75 MHz): d 173.35, 172.96 (C@O), 139.07, 138.57,
138.49, 137.91, 128.26, 128.07, 127.74, 127.69, 127.55,
127.50, 127.45, 127.15 (aromatic-C), 101.69 (C-2),
78.49 (C-3), 76.58 (C-4), 74.99, 73.77 (benzylic-C),
73.59 (C-5), 72.33, 71.29 (benzylic-C), 70.13 (C-1),
69.97 (C-20), 62.49 (C-10), 61.37 (C-6), 59.92 (C-30),
34.25, 34.10 (COCH2), 31.89–22.70 (aliphatic C) and
14.10 (CH3) ppm.
50%), mp 110–112 ꢁC. [a]D ꢀ48 (DMF). MS (FAB-
Na+) m/z 641 (M+Na)+, 458 (M+NaꢀCOC11H23)+,
257 (M+Naꢀ2 · COC11H23, ꢀH2O)+. 1H NMR
(CDCl3+CD3OD, 400 MHz): d 5.20 (m, 1H, H-20),
4.40 (dd, 1H, J3,4, J4,5 3.6 Hz, H-4), 4.18 (d, 1H, J
6.6 Hz, H-1a0), 4.16 (d, 1H, J 6.6 Hz, H-1b0), 3.90 (d,
1H, J 9.8 Hz, H-3), 3.80–3.68 (m, 7H, H-1, H-30, H-5,
H-6), 2.3–2.2 (m, 4H, COCH2), 1.58 (m, 4H,
CH2CH2CH3), 1.26 (m, 32H, aliphatic H) and 0.87
(2 · t, 6H,
J
6.8 Hz, 2 · CH3) ppm. 13C NMR
(CDCl3+CD3OD, 75 MHz): d 173.79, 173.25 (C@O),
100.12 (C-2), 70.20 (C-3), 70.03 (C-4), 69.95 (C-5),
69.11 (C-20), 63.64 (C-1), 62.43 (C-6), 62.29 (C-10),
59.54 (C-30), 34.12, 33.96 (–COCH2), 31.73–22.49
(aliphatic C) and 13.87 (CH3) ppm. Anal. Calcd
for C33H62O10: C, 64.05; H, 10.10. Found: C, 64.40;
H, 9.83.
3.8. 2(R),3-Dihydroxypropyl 10,30,40,50-tetra-O-benzyl-
b-D-fructopyranoside, 2,3-dihexadecanoate [2(R),3-di-
hexadecanoyloxypropyl 10,30,40,50-tetra-O-benzyl-
b-D-fructopyranoside] (9)
Treatment of compound 1 (182 mg, 0.296 mmol) with
hexadecanoylchloride (0.20 mL, 0.888 mmol, 3 equiv)
as described above yielded compound 9 (255 mg,
79%), [a]D ꢀ33.2 (CHCl3) as a pure colourless oil. H
3.10. 2(R),3-Di-tetradecanoyloxypropyl b-D-fructopyran-
oside (11)
1
NMR (CDCl3, 300 MHz): d 7.40–7.21 (m, 20H, aro-
matic H), 5.28 (m, 1H, H-20), 4.91, 4.61 (2d, each 1H,
J 11.5 Hz, benzylic-H), 4.76, 4.73 (2d, each 1H, J
12.7 Hz, benzylic-H), 4.64, 4.43 (2d, each 1H, J 11.9
Hz, benzylic H), 4.60, 4.58 (2d, each 1H, J 11.6 Hz, ben-
zylic-H), 4.31 (d, 1H, J 10.0 Hz, H-3), 4.10 (d, 1H, J
6.2 Hz, H-1a0), 4.00 (d, 1H, 6.2 Hz, H-1b0), 3.94 (dd,
1H, J3,4, J4,5 3.1 Hz, H-4), 3.87 (dd, 1H, J5,6eq 1.7 Hz,
J6ax,6eq ꢀ12.3 Hz, H-6eq), 3.83 (dd, 1H, J5,6ax 1.6 Hz,
J6ax,6eq ꢀ12.3 Hz, H-6ax), 3.77 (m, 1H, H-5), 3.75 (d,
Hydrogenolysis of 8 (836 mg, 0.81 mmol) as described
above gave compound 11 (316 mg, 58%), mp 116 ꢁC
(ether–EtOH), [a]D ꢀ45.4 (DMF). MS (FAB-Na+) m/z
697 (M+Na)+, 514 (M+NaꢀC13H27)+, 285 (M+Naꢀ
C13H27, ꢀCOC13H27, ꢀH2O)+. 1H NMR (CDCl3+
CD3OD, 400 MHz): d 5.22 (m, 1H, H-20), 4.41 (dd,
1H, J3,4, J4,5 3.6 Hz, H-4), 4.20 (d, 1H, J 6.6 Hz, H-
1a0), 4.18 (d, 1H, J 6.6 Hz, H-1b0), 3.92 (d, 1H, J
9.8 Hz, H-3), 3.80–3.68 (m, 7H, H-1, H-30, H-5, H-6),
2.3–2.2 (m, 4H, COCH2), 1.58 (m, 4H, CH2CH2CH3),
1.26 (m, 40H, aliphatic H) and 0.87 (2 · t, 6H,
2 · CH3) ppm. 13C NMR (CDCl3+CD3OD, 75 MHz):
d 173.69, 173.15 (C@O), 100.11 (C-2), 70.19 (C-3),
70.13 (C-4), 69.98 (C-5), 69.11 (C-20), 63.62 (C-1),
62.39 (C-6), 62.25 (C-10), 59.52 (C-30), 34.12, 33.90 (–
COCH2), 31.73–22.49 (aliphatic C) and 13.87 (CH3)
ppm. Anal. Calcd for C37H70O10: C, 65.84; H, 10.45.
Found: C, 65.87; H, 10.57.
0
0
1H, J ꢀ10.2 Hz, H-1a), 3.64 (d, 1H, J3 a;2 6.5 Hz, H-
30a), 3.62 (d, 1H, J ꢀ10.2 Hz, H-1b), 3.58 (d, 1H,
J3 b;2 6.5 Hz, H-30b), 2.3–2.2 (m, 4H, COCH2), 1.60–
1.53 (m, 4H, CH2CH2CH3), 1.25 (m, 48H, aliphatic H)
and 0.87 (2 · t, 6H, J 6.8 Hz, 2 · CH3) ppm. 13C
NMR (CDCl3, 75 MHz): d 173.32, 172.95 (C@O),
139.07, 138.57, 138.48, 137.90, 128.25, 128.06, 127.73,
127.69, 127.54, 127.49, 127.44, 127.14 (aromatic-C),
101.69 (C-2), 78.48 (C-3), 76.57 (C-4), 74.98, 73.77 (ben-
zylic-C), 73.58 (C-5), 72.32, 71.29 (benzylic-C), 70.12 (C-
1), 69.96 (C-20), 62.48 (C-10), 61.37 (C-6), 59.91 (C-30),
34.24, 34.10 (COCH2), 31.90–22.68 (aliphatic C) and
14.10 (CH3) ppm.
0
0
3.11. 2(R),3-Di-hexadecanoyloxypropyl b-D-fructo-
pyranoside (12)
Treatment of compound 9 (200 mg, 0.183 mmol) in the
same above manner yielded 12 (63 mg, 54%), mp
120 ꢁC (ether–EtOH), [a]D +44.4 (DMF). MS (FAB-
Na+) m/z 752 (M+Na)+, 330 (M+Naꢀ2 · C15H31)+,
312 (M+Naꢀ2 · C15H31ꢀH2O)+. 1H NMR (CDCl3+
CD3OD, 400 MHz): d 5.23 (m, 1H, H-20), 4.42 (dd,
1H, J3,4, J4,5 3.6 Hz, H-4), 4.22 (d, 1H, J 6.6 Hz, H-
1a0), 4.19 (d, 1H, J 6.6 Hz, H-1b0), 3.94 (d, 1H, J
9.8 Hz, H-3), 3.80–3.68 (m, 7H, H-1, H-30, H-5, H-6),
2.3–2.2 (m, 4H, COCH2), 1.58 (m, 4H, CH2CH2CH3),
1.26 (m, 48H, aliphatic H), 0.87 (2 · t, 6H, J 6.8 Hz,
2 · CH3) ppm. 13C NMR (CDCl3+CD3OD, 75 MHz):
d 173.76, 173.34 (C@O), 100.13 (C-2), 70.18 (C-3),
3.9. 2(R),3-Di-dodecanoyloxypropyl b-D-fructo-
pyranoside (10)
A solution of compound 7 (253 mg, 0.258 mmol) in
methanol (30 mL) was treated with palladized charcoal
(10%, 60 mg) and then hydrogenated (1 atm) at room
temperature for 2 h. The mixture was filtered through
a layer of Celite, the inorganic material washed with
methanol (10 mL) and the combined filtrate and wash-
ings concentrated in vacuo. The crystalline material
was recrystallized (ether–EtOH) to give 10 (836 mg,

852
F. Sung’hwa et al. / Carbohydrate Research 341 (2006) 846–854
70.12 (C-4), 69.97 (C-5), 69.11 (C-20), 63.63 (C-1), 62.38
(C-6), 62.24 (C-10), 59.53 (C-30), 34.12, 33.90
(–COCH2), 31.73–22.49 (aliphatic C) and 13.87 (CH3)
ppm. Anal. Calcd for C39H74O10: C, 65.86; H, 10.44.
Found: C, 65.89; H, 10.54.
300 MHz): d 7.42–7.21 (m, 20H, aromatic H), 5.68–
5.47 (m, 2H, H-20, H-30), 4.93, 4.62 (2d, each 1H, J
11.3 Hz, benzylic-H), 4.77, 4.74 (2d, each 1H, J 12.6
Hz, benzylic-H), 4.68, 4.40 (2d, each 1H, J 11.9 Hz, ben-
zylic-H), 4.63–4.60 (m, 2H, benzylic-H), 4.36 (d, 1H,
H-3), 4.00–3.93 (m, 3H, H-10a, H-10b, H-4), 3.87 (dd,
1H, J5,6eq 1.8 Hz, J6ax,6eq ꢀ11.9 Hz, H-6eq), 3.83 (m,
1H, H-5), 3.77 (d, 1H, J ꢀ10.1 Hz, H-1a), 3.62 (d, 1H,
J ꢀ10.1 Hz, H-1b), 3.55 (dd, 1H, J5,6ax 1.4 Hz, J6ax,6eq
3.12. But-2-enyl b-D-fructopyranoside (14)
D-Fructose (10.0 g, 55.55 mmol) was added to a stirred
mixture of crotyl alcohol (cis/trans, 1:19; 50 mL) and
acetyl chloride (1.5 mL) and then set aside at room tem-
perature for 48 h. The crystalline material was collected
by filtration, washed with ethanol (20 mL) and ether
(20 mL) and recrystallized from ethanol containing a
few drops of concd aqueous ammonia solution (25%)
to give 14 (8.56 g, 66%), mp 179–180 ꢁC, [a]D ꢀ148
(MeOH), MS (FAB-Na+) m/z 257 (M+Na)+. 1H
NMR (D2O, 300 MHz): d 4.0–3.90 (m, 3H, H-20, H-30,
H-3), 3.89–3.84 (m, 2H, H-4, H-5), 3.79–3.65 (m, 6H,
0
0
ꢀ11.9 Hz, 6ax), 1.65 (d, 3H, J3 ;4 6.4 Hz, CH3)
ppm. 13C NMR (CDCl3, 75 MHz): d 138.91, 138.72,
138.55, 138.01, 128.20, 128.14, 128.00, 127.95, 127.68,
127.67, 127.57, 127.35, 127.21 (aromatic-C), 131.82
(OCH2CH@CH2CH3), 127.88 (OCH2CH@CH2CH3),
101.79 (C-2), 78.87 (C-3), 76.25 (C-4), 75.49 (benzylic-
C), 73.66 (C-5), 73.43, 72.19, 71.07 (benzylic-C),
70.23 (C-1), 62.00 (C-10), 61.05 (C-6), and 17.68 (CH3)
ppm.
3.15. 2(R),3(R)-Dihydroxybutyl 10,30,40,50-tetra-O-benz-
yl-b-D-fructopyranoside (16)
H-1, H-10, H-6), 1.62 (d, 3H, J3 ;4 6.4 Hz, CH3) ppm.
13C NMR (CDCl3, 75 MHz): d 131.72 (–OCH2CH@
CH2CH3), 127.83 (–OCH2CH@CH2CH3), 102.06 (C-
2), 70.85 (C-3), 70.37 (C-4), 69.4 (C-5), 65.17 (C-1),
63.00 (C-10), 62.57 (C-6) and 18.28 (CH3) ppm. Anal.
Calcd for C10H18O6: C, 51.27; H, 7.75. Found: C,
50.95; H, 7.68.
0
0
A mixture of potassium osmate dihydrate (14.49 mg),
K2CO3 (4.04 g), K3Fe(CN)6 (9.75 g), methanesulfona-
mide (941.3 mg) and (DHQD)2PHAL (77 mg) in water
(50 mL) was added gradually to a stirred solution of
compound 13 (5.9 g, 9.9 mmol) in 2-methyl-propan-2-
ol (50 mL). The mixture was stirred vigorously at room
temperature for 4 h, quenched by the addition of
Na2SO3 (15 g), stirred for a further 1 h and then treated
with ether (100 mL) and water (60 mL). The separated
aqueous phase was extracted with ether (2 · 50 mL)
and the combined organic layers were washed sequen-
tially with saturated aqueous sodium chloride, aqueous
2 M KOH solution, dried (MgSO4) and concentrated
in vacuo. Recrystallization (isopropylether) of the crys-
talline residue gave compound 16 (5.1 g, 82%), mp
134–135 ꢁC, [a]D ꢀ52.5 (CHCl3). 1H NMR (CDCl3,
300 MHz): d 7.40–7.20 (m, 20H, aromatic H), 4.90,
4.60 (2d, each 1H, J 11.0 Hz, benzylic-H), 4.73, 4.65
(2d, each 1H, J 12.6 Hz, benzylic-H), 4.62, 4.44 (2d, each
1H, J 11.9 Hz, benzylic-H), 4.30 (d, 1H, J 9.9 Hz, H-3),
4.04–3.97 (m, 2H, benzylic-H), 3.89 (dd, 1H, J3,4, J4,5
3.2 Hz, H-4), 3.88 (dd, 1H, J5,6eq 1.8 Hz, J6ax,6eq
ꢀ12.3 Hz, H-6eq), 3.85 (dd, 1H, J5,6ax 1.6 Hz, J6ax,6eq
ꢀ12.3 Hz, H-6ax), 3.80 (m, 1H, H-20), 3.78 (m, 1H, H-
5) 3.76 (d, 1H, J ꢀ10.2 Hz, H-1a), 3.65 (d, 1H, J
ꢀ10.2 Hz, H-1b), 3.62–3.37 (m, 3H, H-10a, H-10b, H-
3.13. n-Butyl b-D-fructopyranoside (15)
A solution of compound 14 (500 mg, 2.14 mmol) in
water (30 mL) containing one drop of Et3N was treated
with palladized charcoal (5%, 80 mg) and hydrogenated
(1 atm) at rt for 6 h. The inorganic material was
removed by filtration through a thin layer of Celite,
washed with water (20 mL) and the combined filtrate
and washings were concentrated in vacuo to give 15
(450 mg, 89%), mp 156–158 ꢁC (ethanol), [a]D ꢀ146
(MeOH); lit.21 mp 156–158 ꢁC, [a]D ꢀ145 (MeOH).
3.14. But-2-enyl 1,3,4,5-tetra-O-benzyl-b-D-fructo-
pyranoside (13)
A cooled (0 ꢁC), stirred mixture of compound 14 (5.0 g,
21.4 mmol) and finely powdered potassium hydroxide
(5.98 g, 107 mmol, 5 equiv) in Me2SO (25 mL) was trea-
ted with benzyl chloride (12.2 mL, 107 mmol, 5 equiv)
and the mixture set aside at room temperature for ca.
24 h. The mixture was treated with ether (100 mL) and
water (40 mL). The aqueous layer was extracted with
ether (50 mL) and the organic layers washed with satd
aqueous sodium chloride solution (3 · 20 mL), dried
(Na2SO4) and concentrated in vacuo. Column chroma-
tography (hexane–ethyl acetate, 3:1) of the resultant
material gave compound 13 (11.2 g, 88.5%) as a colour-
less oil, [a]D ꢀ50.5 (CHCl3). 1H NMR (CDCl3,
30), 2.97, 1.82 (2 · br s, 2H, OH), 1.17 (d, 3H, J3 ;4
0
0
6.4 Hz, CH3) ppm. 13C NMR (CDCl3, 75 MHz): d
138.51, 138.37, 138.33, 137.70, 128.31, 128.19, 127.87,
127.85, 127.76, 127.67, 127.64, 127.55, 127.53, 127.46
(aromatic-C), 100.97 (C-2), 78.75 (C-3), 76.66 (C-4),
75.50, 73.64 (benzylic-C), 73.30 (C-5), 73.13 (C-20),
72.19, 71.24 (benzylic-C), 70.26 (C-10), 68.51 (C-30),
64.87 (C-1), 61.21 (C-6), 19.58 (CH3) ppm. Anal. Calcd

F. Sung’hwa et al. / Carbohydrate Research 341 (2006) 846–854
853
for C38H44O8: C, 72.59; H, 7.05. Found: C, 72.47; H,
7.06.
54.26; H, 3.46; N, 7.59. Found: C, 54.33; H, 3.29; N,
7.54.
In another experiment compound 13 (2.95 g, 4.95
mmol) was treated as above but in the presence of
(DHQ)2PHAL (38.5 mg) to yield compound 16 (2.74 g,
88%) with the same physical and spectral constants as
reported above.
References
1. van Hummel, H. C. Fortsch. Org. Naturst. 1975, 32, 267–
295.
2. Ishizuka, I.; Yamakawa, T. In New Comprehensive
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Weigandt, H., Eds.; Elsevier: Amsterdam, 1985; Vol. 10,
pp 101–198.
3.16. 2(R),3(R)-Dibenzyloxybutyl 10,30,40,50-tetra-O-
benzyl-b-D-fructopyranoside (17)
3. Curafalo, W. Biochem. Biophys. Acta 1987, 906, 111–
160.
4. Koynova, R. D.; Tenchov, B. G.; Kuttenreich, H.; Hinz,
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A stirred mixture of compound 16 (1.0 g, 1.59 mmol)
and finely powdered KOH (178 mg, 3.18 mmol, 2 equiv)
in Me2SO (10 mL) was treated with benzyl chloride
(0.35 mL, 3.18 mmol, 2 equiv) as described above to give
compound 17 (1.1 g, 87%) as a colourless oil, [a]D ꢀ58.4
(CHCl3), after column chromatography (hexane–ethyl
acetate, 3:1). H NMR (CDCl3, 300 MHz): d 7.43–7.20
(m, 30H, aromatic H), 4.98 (d, 1H, J 11.4 Hz, benz-
ylic-H), 4.77, 4.72 (2d, 2H, J 12.8 Hz, benzylic-H),
5. Sakata, K.; Ina, K. Agric. Biol. Chem. 1990, 47, 2957–
2960.
6. Shirahashi, H.; Murakami, N.; Watanabe, M.; Nagatsu,
A.; Sakakibara, J.; Tokuda, H.; Nishino, H.; Iwashima, A.
Chem. Pharm. Bull. 1993, 41, 1664–1666.
7. Nagatsu, A.; Watanabe, M.; Ikemoto, K.; Hashimoto, M.;
Murakami, N.; Sakakibara, J.; Tokuda, H.; Nishino, H.;
Iwashima, A.; Yazawa, K. Bioorg. Med. Chem. Lett. 1994,
4, 1619–1622.
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211–221.
9. van der Heijden, A. M.; van Rantwijk, F.; van Bekkum,
H. J. Carbohydr. Chem. 1999, 18, 131–147.
1
4.68–4.56 (m, 8H, benzylic-H), 4.45 (1d, 1H,
J
11.9 Hz, benzylic-H), 4.35 (d, 1H, J 10.1 Hz, H-3),
3.96 (dd, 1H, J3,4, J4,5 3.2 Hz, H-4), 3.85–3.53 (m, 9H,
H-1a, H-1b, H-10a, H-10b, H-20, H-30, H-5, H-6eq, H-
6ax), 1.18 (d, 3H, J3 ;4 6.4 Hz, CH3) ppm. 13C NMR
(CDCl3, 75 MHz): d 138.51, 138.37, 138.33, 137.70,
128.31, 128.19, 127.87, 127.85, 127.76, 127.67, 127.64,
127.55, 127.53, 127.46 (aromatic-C), 100.97 (C-2),
78.75 (C-3), 76.66 (C-4), 75.50, 73.64 (benzylic-C),
73.30 (C-5), 73.13 (C-20), 72.6, 72.9, 72.19, 71.24 (ben-
zylic-C), 70.26 (C-10), 68.51 (C-30), 64.87 (C-1), 61.21
(C-6), 19.58 (CH3) ppm.
0
0
´
10. Gonzalez-Munoz, F.; Perez-Oseguera, A.; Cassani, J.;
˜
´
´
Jimenez-Estrada, M.; Vazquez-Duhalt, R.; Lopez-Mun-
guia, A. J. Carbohydr. Chem. 1999, 18, 275–283.
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1967, 22, 229–305.
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272.
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therein.
3.17. 1-Deoxy-D-threitol 2,3,4 tris-p-nitrobenzoate (19)
14. Raaijmakers, H. W. C.; Arnouts, E. G.; Zwanenburg, B.;
Chittenden, G. J. F. Carbohydr. Res. 1994, 257, 293–
297.
15. Gurjar, M. K.; Mainkar, A. S. Tetrahedron: Asymmetry
1992, 3, 21–24.
16. Peci, L. M.; Stick, R. V.; Tilbrook, D. M. G.; Winslade,
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A stirred solution of compound 17 (1.0 g, 1.24 mmol) in
aqueous trifluoroacetic acid (90%, 5 mL) was main-
tained at rt for 10 min. and then concentrated in vacuo.
Column chromatography (hexane–ethyl acetate, 9:2) of
the resultant material gave compound 18 (259 mg,
73%), which was not characterized but dissolved in
MeOH (40 mL), treated with palladized charcoal
(10%, 60 mg) and hydrogenated at rt for 3 h. The inor-
ganic material was removed by filtration through Celite,
washed with MeOH (2 · 20 mL) and the combined fil-
trate and washings concentrated in vacuo. A stirred,
cooled (0 ꢁC) solution of the residue (89 mg) in pyridine
(5 mL) was treated with p-nitrobenzoyl chloride
(662.5 mg, 3.35 mmol) and then set aside at rt for 3 days.
The mixture was concentrated in vacuo and the material
obtained crystallized from CHCl3–MeOH to give 19
(236 mg, 52%) as pale yellow crystals, mp 130–131 ꢁC,
[a]D ꢀ9.0 (CHCl3); lit.26,27 mp 129–131 ꢁC, [a]D ꢀ9.05
(CHCl3). {cf. lit.28 (erythro isomer) mp 159–160 ꢁC,
[a]D +8.1 (CHCl3)}. Anal. Calcd for C25H19O12N3: C,
´
18. Moitessier, N.; Maigret, B.; Chretien, F.; Chapleur, Y.
Eur. J. Org. Chem. 2000, 995–1006.
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