Synthesis of 1-deoxy-L-gulonojirimycin (L-guloDNJ) and 1-deoxy-D-talonojirimycin (D-taloDNJ)

Article abstract of DOI:10.1016/S0008-6215(02)00100-3

Carbohydrate based syntheses of azasugars with unusual configurations viz. 1,5-dideoxy-1,5-imino-L-gulitol (L-guloDNJ) and 1,5-dideoxy-1,5-imino-L-talitol (L-taloDNJ) are reported, from D-mannose and D-fructose, respectively. The key steps in both syntheses involved reductive aminative cyclizations. Thus, L-guloDNJ was obtained by reduction of 2,3;4,6-di-O-isopropylidene-5-O-p-toluenesulfonyl-D-mannononitrile with LiAlH₄ in DME to give the protected azasugar which upon hydrolysis with HCl afforded crystalline L-guloDNJ as the HCl salt in 29% overall yield. Reduction of 6-azido-1-O-tert-butyldimethylsilyl-2,3-O-isopropylidene-β-D- ribohexulofuranose obtained from D-fructose in six steps, followed by treatment with HCl, afforded L-taloDNJ as an HCl salt in ～10% overall yield.

Full text of DOI:10.1016/S0008-6215(02)00100-3

Carbohydrate Research 337 (2002) 1083–1087
www.elsevier.com/locate/carres
Synthesis of 1-deoxy-
L-gulonojirimycin (
L-guloDNJ) and
1-deoxy- -talonojirimycin (
D
D-taloDNJ)
Cosam C. Joseph,† Henk Regeling, Binne Zwanenburg, Gordon J.F. Chittenden*
Department of Organic Chemistry, NSR Center for Molecular Structure, Uni6ersity of Nijmegen, Toernooi6eld 1,
NL-6525 ED Nijmegen, The Netherlands
Received 18 October 2001; accepted 10 April 2002
Abstract
Carbohydrate based syntheses of azasugars with unusual configurations viz. 1,5-dideoxy-1,5-imino-
1,5-dideoxy-1,5-imino- -talitol ( -taloDNJ) are reported, from -mannose and -fructose, respectively. The key steps in both
syntheses involved reductive aminative cyclizations. Thus, -guloDNJ was obtained by reduction of 2,3;4,6-di-O-isopropylidene-5-
O-p-toluenesulfonyl- -mannononitrile with LiAlH4 in DME to give the protected azasugar which upon hydrolysis with HCl
afforded crystalline -guloDNJ as the HCl salt in 29% overall yield. Reduction of 6-azido-1-O-tert-butyldimethylsilyl-2,3-O-iso-
propylidene-b- -ribohexulofuranose obtained from -fructose in six steps, followed by treatment with HCl, afforded -taloDNJ
as an HCl salt in ꢀ10% overall yield. © 2002 Elsevier Science Ltd. All rights reserved.
L-gulitol (L-guloDNJ) and
L
L
D
D
L
D
L
D
D
L
Keywords: Azasugars; Iminosugars; Glycosidase inhibitors; L-guloDNJ; D-taloDNJ
1. Introduction
Azasugars (also termed imino sugars) are an impor-
tant class of inhibitors of glycosidases and glycosyl
processing enzymes which continue to attract consider-
able attention.1 Many of them are excellent agents for
HIV/AIDS, cancer, and diabetes therapy.1,2 Many syn-
theses of azasugars have been focused on derivatives
Compound 1 has been obtained5 during degradative
analysis of a capsular polysaccharide. It was isolated as
an amorphous hydroacetate. A synthesis has also been
D-mannose in eight steps; the product
required separation from an enantiomer. It has been
obtained in admixture with 1,5-dideoxy-1,5-mannojir-
with
ses of
D
-gluco or
-guloDNJ (1) and
D
-manno configurations.1,2 The synthe-
-taloDNJ (2) are among the
L
D
described6 from
least of those reported. The biological activity of 1 has
not yet been fully established. It is a constituent entity
of a novel disaccharide 3, a potent a-glycosidase in-
imycin (DMJ) and
D
icz reaction as a peracetate.8
D-manno-azepane derivatives from
hibitor.3 It is thought that
-guloDNJ (1) could also be
L
-mannitol7 and more recently, via an aza-Achmatow-
a potent glycosidase inhibitor and further efforts need
to be made to find alternative syntheses and to evaluate
The earlier syntheses of compound 2 utilized a
chemo-enzymatic approach.9a,9b It has also been ob-
tained via a syn-aldol condensation of a protected
its biological activities. Compound 4, the
has also been shown to be a potent a-glucosidase and
a-
-fucosidase inhibitor.4
L
isomer of 2,
L
D
-erythrose derivative with stannous salts of substituted
dimethoxydihydropyrazine derivatives.10 As part of a
programme to devise simplified routes to a number of
azasugar derivatives, alternative syntheses of 1 and 2
* Corresponding author. Tel.: +31-24-3653204; fax: +31-
24-3653393.
E-mail address: gjfc@sci.kun.nl (G.J.F. Chittenden).
† Present address: Department of Chemistry, University of
Dar es Salaam, PO Box 35061, Dar es Salaam, Tanzania.
from
D-mannose and D-fructose, respectively, using
readily available reagents, are reported.
0008-6215/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(02)00100-3

1084
C.C. Joseph et al. / Carbohydrate Research 337 (2002) 1083–1087
2. Results and discussion
fructopyranose (10).15 Compound 12 was obtained
from pure 10, via the diulose 11 using a known16
oxidation-selective reduction sequence. Treatment of 12
with 2,2-dimethoxypropane in acetone, in the presence
of a catalytic quantity of 70% perchloric acid, gave the
thermodynamically more stable re-arrangement product
13 (92.5%). The C-6 primary hydroxyl group of com-
pound 13 was converted into the corresponding azido
The synthesis of
L
-guloDNJ (1) from
D-mannose
required an aminative-cyclization process between C-1
and C-5, with inversion of configuration at C-5. This
was achieved using the known11 lactone 7, readily ob-
tainable by oxidation of the diacetal 6. The direct
isopropylidenation
of
D
-mannose
with
2-
derivative,
6-azido-6-deoxy-1,2;4,5-di-O-isopropyli-
methoxypropene under carefully controlled conditions
to give compound 6 has been described.12 Difficulties
were experienced in obtaining consistent yields using
this procedure. We decided to investigate a modified
dene-b-
D
-ribohexulofuranose (15) using two different
procedures. The first method,17 which is a one-pot
reaction sequence, involved treatment of compound 13
with 1-methyl-2-fluoropyridinium tosylate followed by
approach for preparing 6. Thus,
D-mannose was re-
18
reaction with LiN3 in 1-methyl-2-pyrrolidinone to
acted with benzyl alcohol in the presence of BF3–
methanol complex (50–52%, BF3) and the crude
material obtained was treated with a mixture of 2,2-
dimethoxypropane and acetone containing p-toluene-
sulfonic acid. Catalytic hydrogenolysis of the product 5
in the presence of palladized charcoal (10%) gave the
known diacetal 6 in 67.5% overall yield. Standard
Swern oxidation13 of 6 gave the lactone 7. Treatment of
7 in 1:1 ammoniacal methanol solution with ammonia
gas at 0 °C followed by reaction of the crude product
with excess p-toluenesulfonyl chloride in anhydrous
pyridine gave the activated nitrile derivative 8. Reduc-
tion of 8 with LiAlH4 in 1,2-dimethoxyethane at 0 °C
occurred with concomitant cyclization to give the pro-
tected azasugar 9 which on hydrolysis with HCl af-
give compound 15 (\80%). The second procedure
involved treatment of 13 with p-toluenesulfonyl chlo-
ride–pyridine in the usual manner,19 to give the tosylate
derivative 14, followed by reaction with LiN318 in DMF
at ꢀ40 °C to afford 15 in 76% yield, for the two-stage
process. The beneficial use of LiN3 in nucleophilic
displacement reactions has been reviewed.20 The follow-
ing step in the projected synthesis of 2 required removal
of the 1,2-O-isopropylidene group from 15. Acid hy-
drolysis of 1,2-O-acetal groups of ketose derivatives is
sometimes problematical21 leading to considerable de-
composition. Mild acetolysis of the 1,2-O-isopropyli-
dene group of compound 15 by treatment with acetic
anhydride in the presence of a catalytic quantity of
BF3–etherate gave the diacetate 16. Deacetylation
(Zemple´n) of 16 followed by reaction with tert-
butyldimethylsilylchloride–imidazole gave the selec-
tively protected compound 17. It was noteworthy that
the 3,4-O-isopropylidene group of 15 remained unaf-
fected by this treatment, which indicated the stability of
the cis-fused 5:5 bicyclic ring system. Catalytic hydro-
genation (Pd–C) of 17 in EtOH afforded 6-O-tert-
forded crystalline -guloDNJ (1) as its HCl salt in 29%
L
overall yield. The route compares favorably with pre-
existing ones and could be used to produce 1 in consid-
erable quantities if required (Scheme 1).
The envisaged route to compound 2 was from
tose via 1,2;4,5-di-O-isopropylidene-b- -ribohexulo-
furanose (13). The use of -fructose for the synthesis of
azasugars is rather limited. It has been used in a simple
synthesis of 1-deoxymannojirimycin.14 Treatment of
D-fruc-
D
D
butyldimethylsilyl-1-deoxy-3,4-O-isopropylidene-
ojirimycin (18). Treatment of compound 18 with HCl in
MeOH gave -taloDNJ (2), as the HCl salt in ꢀ10%
D-talon
D
-
fructose with acetone in the presence of a catalytic
amount of elemental iodine at room temperature gave
D
overall yield. Efforts were made to crystallize the free
azasugar or the HCl salt from various solvent mixtures.
These were mainly unsuccessful, but the compound
eventually crystallized well from MeOH–ether, but at-
tempts to dry the resulting material proved to be ex-
tremely difficult as the crystals were highly deliquescent
(Scheme 2).
the kinetically favored 1,2;4,5-di-O-isopropylidene-b-D-
3. Experimental
Melting points were determined using a Reichert
thermopan microscope equipped with cross polarizers
and are uncorrected. IR spectra were determined on a
Perkin–Elmer 298 spectrophotometer. Optical rota-
tions were determined with a Perkin–Elmer automatic
polarimeter model 241 MC on 1% solutions in the
Scheme 1. Reagents and conditions: (a) BnOH–BF3, MeOH
(b) DMP–Me2CO, TsOH (c) H2, Pd–C (d) Me2SO–TFAA,
CH2Cl2 (e) NH3–NH4OH, MeOH (f) TsCl, Py (g) H2,
LiAlH4, DME, 0 °C (h) HCl.

C.C. Joseph et al. / Carbohydrate Research 337 (2002) 1083–1087
1085
Scheme 2. Reagents and conditions: (a) Me2CO–I2 (b) TFAA–Me2SO, CH2Cl2 (c) NaBH4–EtOH (d) DMP–Me2CO, HClO4 (e)
1-methyl-2-fluoropyridinium toluenesulfonate, LiN3–1-methyl-2-pyrollidinone or (f) TsCl–Py, (g) LiN3–DMF (h) Ac2O–
BF3·OEt2 (i) NaOMe–MeOH, TBDMSCl–DMF, imidazole (j) H2, Pd–C, EtOH (k) HCl–MeOH.
2,3;4,6-Di-O-isopropylidene-D-mannono-1,5-lactone
solvents indicated. Column chromatography was per-
formed using Silica Gel (E. Merck) using the eluents
indicated. Thin-layer chromatography (TLC) on pre-
coated plates of Silica Gel GF254 (E. Merck) was con-
ducted in the solvent mixtures given. Compounds were
detected by spraying with 3% H2SO4 in EtOH followed
(7).—Treatment of 6 under standard Swern oxidation13
conditions gave pure 7 (3.3 g, 82.8%) as fine fiber-like
crystals: mp 200–201 °C (petroleum ether, 80–100 °C),
lit.11 mp 202 °C; [h]D +46.4° (CHCl3), lit.11 [h]D
+43.5°.
1
by heating at 140 °C. H and 13C NMR were recorded
2,3;4,6-Di-O-isopropylidene-5-O-p-toluenesulfonyl-D-
mannononitrile (8).—A stirred cooled solution of the
lactone 7 (3 g, 11.58 mmol) in a mixture of MeOH (30
mL) and 25% aq ammonia solution (30 mL) was
treated with ammonia gas for 10 min and then left to
stir at rt for 30 min. The mixture was concentrated in
vacuo to give a colorless foam which was dissolved in
anhyd pyridine (30 mL), cooled to 0 °C, treated with
tosyl chloride (8.83 g, 46.33 mmol, 4 equiv), and after a
further 1 h at this temperature, was set aside at ca. 5 °C
for 5 days. The mixture was poured into ice water (200
mL) and the resultant white solid was collected by
filtration and recrystallized (MeOH) to give the nitrile 8
(3.4 g, 71.4%): mp 129–131 °C; [h]D −11.06° (CHCl3);
1H NMR (CDCl3, 400 MHz): l 7.84, 7.34 (ABq, 4 H,
aromatic H), 4.8 (d, 1 H, J2,3 4.72 Hz, H-2), 4.75 (t, 1
H, J4,3 9.2, J4,5 9.0 Hz, H-4), 4.28 (ddd, 2 H, J6,5 6.8,
J6a,6b 12.7 Hz, H-6a, H-6b), 4.2 (t, 1 H, J3,2 4.9, J3,4 9.0
Hz, H-3), 4.10 (m, 1 H, H-5), 2.4 (s, 3 H, tosyl Me),
1.48, 1.35, 1.14, 1.30 (4s, each 3 H, CMe2). 13C NMR
(CDCl3, 75 MHz): l 144.90, 133.62,129.33, 128.65,
(Carom), 116.59 (CꢀN), 111.42 and 111.336 (2qC), 80.27
(C-2), 77.48 (C-3), 74.34 (C-4), 67.95 (C-6), 66.48 (C-5),
26.38, 25.67, 25.58, 25.45 (2×CMe2) and 21.60 (tosyl
Me). Anal. Calcd for C19H25NSO7: C, 55.46; H, 6.12;
N, 3.40; S, 7.79. Found: C, 55.32; H, 6.07; N, 3.47; S,
7.92.
on Brucker AC 100 (100 MHz), AC 300 (300 MHz)
and Varian AM 400 (400 MHz) spectrometers at rt on
solutions in CDCl3 (internal Me4Si) or D2O (external
1,4-dioxane, 76.8 ppm). 1-Methyl-2-fluoropyridinium
tosylate was purchased from Aldrich.
2,3;4,6-Di-O-isopropylidene-
D
-mannopyranose (6).—
A stirred suspension of -mannose (10 g) in benzyl
D
alcohol (200 mL) was treated with BF3·MeOH complex
(50–52%, BF3; 1.4 mL) and the mixture was main-
tained overnight at ca. 75 °C. The cooled mixture was
neutralized with solid NaHCO3 (pH paper), filtered,
and concentrated in vacuo to give an oil which was
dissolved in water (200 mL), extracted with ether (2×
150 mL), and the aqueous layer was decolorized by
treatment with charcoal, concentrated in vacuo and
EtOAc (2×50 mL), and distilled from the residue to
give a pale brown syrup. A stirred solution of the
resultant material in acetone (70 mL) and 2,2-
dimethoxypropane (70 mL) was treated with p-toluene-
sulfonic acid monohydrate (40 mg) and set aside at rt
for 4 h, when analysis (TLC; 3:2 1,2-dimethoxyethane–
cyclohexane) indicated completeness of reaction. The
mixture was neutralized (NaHCO3), filtered, concen-
trated in vacuo, and a solution of the crude product in
EtOH (40 mL) was hydrogenated (1 atm) in the pres-
ence of palladium charcoal (10%, 600 mg) for 48 h. The
mixture was filtered through Celite, the inorganic mate-
rial washed with EtOH and the combined filtrate and
washings concentrated in vacuo. Column chromatogra-
phy (3:1 hexane–EtOAc) of the residue gave pure 6 (9.7
g, 67.5%): mp 137–140 °C (petroleum ether, 80–
100 °C), lit.12 mp 139–141 °C; [h]D −33.2° (CHCl3),
lit.12 [h]D −39° (CHCl3).
1-Deoxy-2,3;4,6-di-O-isopropylidene-L-gulonojirimycin
(9).—A solution of the nitrile 8 (1.75 g, 4.26 mmol) in
dry 1,2-dimethoxyethane (20 mL) was added dropwise
over 10 min to a stirred, cooled (0 °C) suspension of
LiAlH4 (0.647 g, 17.03 mmol, 4 equiv) in 1,2-
dimethoxyethane (20 mL) maintained under nitrogen.
The mixture was set aside for 4 h, diluted with 1,2-
dimethoxyethane (40 mL), treated dropwise over 15

1086
C.C. Joseph et al. / Carbohydrate Research 337 (2002) 1083–1087
min with water (6 mL), set aside for 30 min, filtered
through a layer (ꢀ1 cm) of MgSO4, and the inorganic
material was washed with 1,2-dimethoxyethane (10
mL). The combined filtrate and washings were concen-
trated in vacuo to yield a colorless syrup (1.12 g), which
crystallized on standing. Recystallization (diisopropyl
ether) gave 9 (0.860 g, 83%): mp 55–57 °C; [h]D
−23.8° (CHCl3); 1H NMR (CDCl3, 300 MHz): l 4.75–
4.71 (m, 1 H, H-2), 4.50 (dd, 1 H, H-4), 4.05 (m, 2 H,
H-6a, H-6b), 3.85 (t, 1 H, H-5), 3.15 (dd, 1 H, H-3),
3.06 (t, 2 H, H-1). 13C NMR (CDCl3, 75 MHz): l
111.50 and 109.34 (2×qC), 83.93 (C-2), 82.130 (C-3),
75.90 (C-4), 66.80 (C-5), 66.76 (C-6), 53.08 (C-1), 26.42,
25.28, and 24.14 (CMe2). Anal. Calcd for C12H21NO4:
C, 59.24; H, 8.70; N, 5.76. Found: C, 59.00; H, 8.57; N,
5.64.
H-5), 4.06 (d, 1 H, J4,3 9.8 Hz, H-4, H-3), 3.54 (dd, 1 H,
J6,5 7.56, J6a,6b 12.5 Hz, H-6a, H-6b), 3.30 (dd, 1 H, J6,5
7.13, J6b,a 12.8 Hz, H-6b, H-6a), 1.44, 1.43, 1.34, 1.32
(4s, each 3 H, CMe2). 13C NMR (CDCl3, 75 MHz): l
113.8 (C-2), 112.92, 111.92 (2×qC), 85.19 (C-5), 84.08,
82.32 (C-3, C-4), 53.22 (C-6), 26.4, 26.36, 26.20, 25.10
(4×CMe2).
Method B. A stirred solution of 1419 (2.0 g, 4.83
mmol) in DMF (10 mL) containing LiN3 (0.71 g, 14.5
mmol) was maintained at 40 °C for 6 days. The mixture
was poured into a mixture of ice-water (30 mL) and
ether (30 mL). The separated aqueous layer was ex-
tracted with ether (3×30 mL) and the combined or-
ganic layers were washed with brine (30 mL), dried
(Na2SO4), and concentrated in vacuo. Column chro-
matography (3:2 1,2-dimethoxyethane–cyclohexane) of
the resultant material gave 15 (1.05 g, 76%) as an oil:
[h]D +38° (CHCl3). The spectral characteristics were
identical to those given above.
1-Deoxy- -gulonojirimycin.HCl (1).—A stirred solu-
L
tion of a portion of the foregoing product (100 mg) in
MeOH (20 mL) containing concd HCl (5 drops) was
maintained at rt for 18 h, when charcoal (20 mg) was
added. The mixture was heated under reflux for 20 min,
cooled, filtered, the residue washed with MeOH (10
mL), and the combined filtrate and washings were
concentrated in vacuo to give a colorless gum. The
crude gum was crystallized from MeOH–ether to give
1·HCl salt (103 mg, 90%): mp 143 °C, lit.2 (free base)
mp 150–151 °C; [h]D −45.0° (MeOH), lit.2 (free base)
1,2-Di-O-acetyl-3,4-O-isopropylidene-6-azido-6-de-
oxy-i- -ribohexulofuranose (16).—A stirred, cooled
D
(0 °C) solution of the azide 15 (4.3 g, 15.08 mmol) in
Ac2O (74 mL) containing BF3·OEt2 (0.37 mL) was set
aside for 2 h. The mixture was then poured into ice cold
satd aq NaHCO3 solution with vigorous stirring and
left to stand at rt until effervescence had ceased. The
mixture was extracted with CH2Cl2 (2×100 mL) and
the combined organic extracts dried (Na2SO4) and con-
centrated in vacuo to give a crude syrup. Column
chromatography (3:1 hexane–EtOAc) of the crude ma-
terial gave compound 16 as a colorless syrup (4.8 g,
94.7%): [h]D +16.4° (CHCl3); IR(neat) wmax 2100
1
[h]578 −21° (water); H NMR (D2O, 300 MHz): l 4.31
(m, 1 H, H-2), 4.21 (dd, 1 H, H-4), 3.80–3.75 (m, 1 H,
H-3), 3.66–3.61 (m, 1 H, H-5), 3.56–3.49 (m, 1 H,
H-6a, H-6b), 3.21–3.15 (m, 1 H, H-6a, H-6b), 3.04–
3.00 (m, 1 H, H-1a, H-1b), 2.87–2.82 (m, 1 H, H-1a,
H-1b). 13C NMR (D2O, 75 MHz): l 74.57(C-5), 71.69/
70.19 (C-3, C-4), 65.82 (C-1), 64.19 (C-2), 52.29 (C-6).
Anal. Calcd for C6H14ClNO4: C, 36.10; H, 7.07; N,
7.02. Found: C, 35.92; H, 6.98; N, 6.91.
1
(NꢂNꢂN), 1740 (CꢂO) cm−1; H NMR (CDCl3, 300
MHz): l 4.95 (d, 1 H, J3,4 6.07 Hz, H-3), 4.76 (dd, 1 H,
J4,5 2.35 Hz, H-4), 4.65 (d, 1 H, J1a,1b 11.94 Hz, H-1a),
4.58 (d, 1 H, H-1b), 4.36 (td, 1 H, H-5), 3.55 (dd, 1 H,
J6a,5 6.98, J6a,6b 12.71 Hz, H-6a), 3.35 (dd, 1 H, J6b,5
6.24 Hz, H-6b), 2.1, 2.08 (s, 6 H, 2×CH3CO), 1.51,
1.33 (2s, each 3 H, CMe2). 13C NMR (CDCl3, 300
MHz): l 170.0, 169.20 (2×CH3CO), 114.14 (C-2),
110.64 (qC-acetal), 86.41 (C-5), 85.30, 82.02 (C-3, C-4),
62.43 (C-1), 52.74 (C-6), 26.44, 25.00 (C(CH3)2 acetal),
21.91, 20.78 (2×CH3CO).
6-Azido-6-deoxy-1,2;3,4-di-O-isopropylidene-i-
D-ri-
bohexulofuranose (15)
Method A. Compound 1316,19 (5.12 g, 19.69 mmol)
was added to a stirred suspension of 1-methyl-2-
fluoropyridinium toluenesulfonate (6.13 g, 21.66 mmol,
1.1 equiv) in CHCl3 (200 mL) containing triethylamine
(3 mL). The mixture was stirred for 1 h and then
concentrated in vacuo to give a yellowish–orange syrup
which was dissolved in 1-methyl-2-pyrrolidinone (50
6-Azido-1-O-tert-butyldimethylsilyl-3,4-O-isopropyli-
dene-i- -ribohexulofuranose (17).—A stirred solution
D
18
mL) treated with LiN3 (4.82 g, 98.46 mmol, 5 equiv)
of compound 16 in MeOH (60 mL) was treated with
0.5% methanolic NaOMe (17 mL) and after a period of
5 min was neutralized with Amberlite IR-120 ion-ex-
change resin (H+ form), filtered and the filtrate concen-
trated in vacuo. Column chromatography (1:1
hexane–EtOAc) of the brown residue gave a colorless
syrup (2.35 g) which was dissolved in DMF (10 mL),
cooled to 0 °C, treated with a mixture of tert-
butyldimethylsilylchloride (5.06 g, 33.57 mmol) and
imidazole (6.52 g, 96.0 mmol) and, after 5 min, was set
aside at rt for a further 30 min. Ether (200 mL) was
and maintained at 80 °C for 2 h. The cooled mixture
was poured into ice-water (150 mL), extracted with
ether (2×150 mL), and the combined ether extracts
washed with brine (60 mL), dried (Na2SO4), and con-
centrated in vacuo. Column chromatography (1:1 hex-
ane–EtOAc) of the residue gave 15 as a colorless syrup
(4.6 g, 82%): [h]D +4.0° (CHCl3); IR(neat) wmax 2100
1
(ꢁNꢂNꢂN) cm−1; H NMR (CDCl3, 300 MHz): l 4.6
(dd, 2 H, J1a,1b 6.3, J1a,1b 12.2 Hz, H-1a, H-1b), 4.33 (d,
1 H, J3,4 9.8 Hz, H-3, H-4), 4.20 (t, 1 H, J5,6 7.10 Hz,

C.C. Joseph et al. / Carbohydrate Research 337 (2002) 1083–1087
1087
added to the mixture which was then washed succes-
sively with water (3×50 mL), brine (50 mL), dried
(Na2SO4), and concentrated in vacuo to give compound
17 (2.80, 81.0%) as a colorless syrup: [h]D −12.7°
(ddd, 1 H, H-2) 3.20 (dd, 1 H, H-1b). 13C NMR (D2O,
75 MHz): l 70.03 (C-3), 69.53 (C-4), 69.04 (C-2), 62.80
(C-6), 61.56 (C-5), 50.73 (C-1).
1
(CHCl3); H NMR (CDCl3, 300 MHz): l 4.62 (m, 2 H,
H-6), 4.25 (t, 1 H, J5,6 7.43, 7.02 Hz, H-5), 4.12 (br s,
OH), 3.80 (dd, 1 H, J1a,1b 10.54 Hz, H-1a, H-1b), 3.63
(m, 1 H, J1b,1a 9.2 Hz, H-1b, H-1b), 3.42 (d, 1 H, J3,4
5.1 Hz, H-3, H-4), 3.20 (dd, 1 H, J4,3 6.6 Hz, H-4, H-3),
1.46, 1.31 (2s, each 3 H, CMe2), 0.92, 0.91 (2s, 9 H,
CMe3), 0.12, 0.09 (s, 6 H, 2 SiMe2). 13C NMR (CDCl3,
75 MHz): l 112.74 (C-2), 105.98 (qC-acetal), 85.35
(C-1), 84.89, 82.69 (C-3, C-4), 64.61 (C-5), 53.42 (C-6),
26.52, 26.31 (2×CMe2), 25.73, 25.14, 24.95 (3×CMe3-
tert-butyl), 2×18.22 (2×SiMe2).
Acknowledgements
C.C. Joseph is grateful to NUFFIC/MHO for finan-
cial support.
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1
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