Synthesis of L-arabinitol and xylitol monomers for the preparation of polyamides. Preparation of an L-arabinitol-based polyamide

Article abstract of DOI:10.1016/S0008-6215(01)00137-9

Dihydrochlorides of 1,5-diamino-1,5-dideoxy-2,3,4-tri-O-methyl-L-arabinitol (and xylitol) and pentachlorophenyl esters of 2,3,4-tri-O-methyl-L-arabinaric (and xylaric) acids have been prepared as suitable bifunctional monomers for linear polycondensations

Full text of DOI:10.1016/S0008-6215(01)00137-9

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Carbohydrate Research 333 (2001) 95–103
Synthesis of
L-arabinitol and xylitol monomers for the
preparation of polyamides. Preparation of an
-arabinitol-based polyamide
L
Mar´ıa de Gracia Garc´ıa-Mart´ın, Roc´ıo Ruiz Pe´rez, Elena Benito Herna´ndez,
Juan A. Galbis*
Departamento de Qu´ımica Orga´nica y Farmace´utica, Facultad de Farmacia, Uni6ersidad de Se6illa,
E-41071 Se6ille, Spain
Received 27 March 2001; accepted 15 May 2001
Abstract
Dihydrochlorides of 1,5-diamino-1,5-dideoxy-2,3,4-tri-O-methyl-
esters of 2,3,4-tri-O-methyl- -arabinaric (and xylaric) acids have been prepared as suitable bifunctional monomers
for linear polycondensations. A new aregic AABB-type -arabinitol-based polyamide is also described from the
L-arabinitol (and xylitol) and pentachlorophenyl
L
L
corresponding monomers. It was crystalline with Tm 250 °C, optically active, and soluble in the usual organic
solvents, including chloroform, and in water. Its Mw obtained by GPC was 27,500 with a polydispersity of 1.4.
© 2001 Elsevier Science Ltd. All rights reserved.
Keywords: Bifunctional carbohydrate-based monomers; L-Arabinitol-based polyamide; Polycondensation reaction; Optically active
polyamide
1. Introduction
galactose, 2-amino-2-deoxy-
D
-glucose,
L
-ara-
binose and -xylose, which were transformed
D
For the last few years, we have been explor-
ing the utility of some easily available
monosaccharides to build high-molecular-
weight materials with potential biocompatibil-
ity and biodegradability. Such carbohy-
drate-based polymers are considered useful
materials for medical applications.1 Several
contributions to the synthesis of polymers
derived from carbohydrate monomers have
been made.2–5 We have described a number of
optically active carbohydrate-based polymers
into the appropriate active monomers for
polymerization reactions.6
In this paper, we describe the preparation
of the dihydrochlorides of 1,5-diamino-
1,5-dideoxy-2,3,4-tri-O-methyl- -arabinitol
(10A) and 1,5-diamino-1,5-dideoxy-2,3,4-tri-
O-methyl-xylitol (10X). We also describe the
preparation of 2,3,4-tri-O-methyl- -arabinaric
acid (11A) and 2,3,4-tri-O-methyl-xylaric acid
(11X) as well as their pentachlorophenyl ester
derivatives 13A and 13X, respectively. Com-
pounds 10A, 10X, 13A, and 13X are bifunc-
tional monomers for linear polyconden-
sations. We present the results of the polycon-
densation between 13A and 10A and the
physico-chemical characterization of the re-
sulting polyamide 14.
L
L
starting from
D
-glyceraldehyde,
D
-glucose,
D
-
* Corresponding author. Tel.: +34-5-4556737; fax: +34-
54-4233765.
E-mail address: galbis@cica.es (J.A. Galbis).
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(01)00137-9

96
M.G. Garc´ıa-Mart´ın et al. / Carbohydrate Research 333 (2001) 95–103
2. Results and discussion
yields. This procedure is easier than the classi-
cal method previously described.8–10
The synthesis of diamines 10A and 10X was
Reduction of 3A and 3X with sodium boro-
hydride afforded the 1,5-diols 4A and 4X in
excellent yields. These were transformed into
the corresponding active derivatives for nucle-
ophilic displacement with sodium azide
(Scheme 2). Reaction of the primary alcohol
function of 4A and 4X with tosyl chloride in
dry pyridine at 0 °C gave the di-O-tosyl
derivatives 5A and 5X in good yield. However,
the two diols behaved differently with mesyl
chloride in dry pyridine at 0 °C. Thus, arabini-
tol 4A gave the expected di-O-mesyl derivative
6A in high yield, but xylitol 4X gave the
racemic mixture of cyclic compounds 7X and
8X in 63% yield, after purification by column
chromatography. This difference of reactivity
between the two diols can be explained in
terms of conformational properties of the aldi-
tol chains.11–13 We assigned the furanoid
structure to these compounds on the basis of
their NMR spectra. This racemic mixture
could be obtained from the meso di-O-mesyl
derivative 6X, previously formed, by attack
either of O-4 at C-1 or of O-2 at C-5. How-
ever, when xylitol 4X reacted with mesyl chlo-
ride in dichloromethane in the presence of
triethylamine, at 0 °C, the di-O-mesyl xylitol
derivative 6X was obtained in 78% yield after
column chromatography. This product was
very unstable, and gradually became polluted
by the cyclic compounds 7X and 8X on stor-
ing at room temperature.
carried out from
L
-arabinose and
D
-xylose in
seven steps. First, we obtained (Scheme 1)
benzyl b- -arabinopyranoside (1A) and benzyl
a-
L
D
-xylopyranoside (1X) by the classical Fis-
cher and Beensch glycoside synthesis;7 further
methylation with methyl iodide and potassium
hydroxide in dimethyl sulfoxide gave 2A and
2X, respectively. Hydrogenolysis of the O-
benzyl glycoside group of 2A and 2X gave the
tri-O-methyl pyranosides 3A and 3X, in high
Scheme 1.
The diazido derivatives 9A and 9X were
better obtained from the corresponding mesyl
derivatives 6A and 6X by reaction with
sodium azide in dimethylformamide at 70 °C
(Scheme 3). Although, formation of a small
proportion of anhydroalditol derivatives was
detected under these conditions, the diazido
derivatives 9A and 9X could be isolated in
good yields. The reaction of the less reactive
di-O-tosyl derivatives 5A and 5X with sodium
azide required higher temperature (100 °C),
and higher amounts of the cyclic compounds
were formed, which made the isolation of the
diazido derivatives 9A and 9X more difficult.
Reduction of 9A and 9X with lithium alu-
minium hydride in tetrahydrofuran followed
Scheme 2.

M.G. Garc´ıa-Mart´ın et al. / Carbohydrate Research 333 (2001) 95–103
97
spectively, in very high yields (Scheme 5), both
previously characterized as dimethyl esters.14,15
The active dipentachlorophenyl esters 13A
and 13X were easily obtained from the corre-
sponding glycaric acid with pentachloro-
phenol and dicyclohexylcarbodiimide in
dichloromethane.
We carried out several polycondensation re-
actions of the active ester 13A with the di-
amine 10A under different conditions (Table
1) to obtain the polyamide 14 (Scheme 6). The
best results were obtained by using the di-
amine dihydrochloride and N-methylpyrro-
lidinone (NMP) as solvent and N-ethyl-
N,N-diisopropylamine (EDPA) as a base, at
45 °C for 4 days. At room temperature, we
obtained a polyamide of lower molecular
weight. The synthesis of stereoregular AABB-
type polyamides by condensation of a diacid
with a diamine requires the existence of a
twofold axis of symmetry in the monomers.
Since 10A and 13A are asymmetric molecules,
their polycondensation should lead to an
aregic, non-stereoregular polyamide due to the
non-regioselective additions of the monomers,
which was confirmed by its 13C NMR spec-
trum. Thus, we observed three signals (one of
them double) for the carbonyl groups, corre-
sponding to the four stereochemical possibili-
ties for the dyads centered on the arabinaric
unit (Scheme 7). The polyamide 14 was opti-
cally active, and it was soluble in the usual
organic solvents, including chloroform, and
very soluble in water. The thermal behavior of
this polyamide was studied by differential
scanning calorimetry (DSC). In all experi-
ments, broad endotherms associated with
melting appeared during the first heating cy-
cle. Several peaks were observed in these
traces, a common feature with polyamides
usually interpreted as due to the fusion of
several populations of different-sized crystal-
lites.16 When 14 was annealed at 165 °C for 3
h, it produced a trace consisting of a single
peak at a higher temperature than that ob-
served in the heating traces of the untreated
samples. The melting point (Tm) of the
polyamide was taken as the maximum of the
peak appearing at 250 °C (DH=39.5 J/g).
The occurrence of such a well-defined melting
peak indicates the ability of 14 to produce
well-formed crystallites despite the non-stere-
Scheme 3.
Scheme 4.
Scheme 5.
by treatment with hydrogen chloride gave the
diamine hydrochlorides 10A and 10X in very
good yields (Scheme 4). In order to obtain
10A and 10X, we also tried the reduction of
diamides 12A and 12X14,15 with borane and
with lithium aluminium hydride, but complex
mixtures of products were formed in all cases.
Oxidation of 3A and 3X with nitric acid at
70–80 °C gave tri-O-methyl-
tri-O-methyl-xylaric acids 11A and 11X, re-
L
-arabinaric and

98
M.G. Garc´ıa-Mart´ın et al. / Carbohydrate Research 333 (2001) 95–103
Table 1
Different conditions for the preparation of polyamide 14
a
Diamine (10A)
Solvent
Temperature (°C)
Time (days)
Yield (%)
Mw
Mw/Mn
Dihydrochloride
Dihydrochloride
Dihydrochloride
Dihydrochloride
Free base
NMP (EDPA)
CHCl3 (EDPA)
DMF (EDPA)
HMPA (EDPA)
NMP
45
25
25
45
45
25
4
2
2
4
5
5
77
55
70
70
70
30
27,500
11,900
11,100
5100
1200
3300
1.4
1.6
1.5
1.4
1.4
1.2
Free base
CHCl3
a Determined by GPC analysis with polystyrene standards using CHCl3 as a mobile phase.
oregular microstructure anticipated for this
polyamide.
sphere on a DSC instrument calibrated with
indium. Samples of about 2–3 mg weight were
heated at a rate of 20 °C/min and cooled at
different rates depending on the purpose.
Benzyl
2,3,4-tri-O-methyl-i- -arabinopy-
L
ranoside (2A).—To a solution of 1A7 (10.66 g,
44 mmol) in dry Me2SO (70 mL) were added
freshly powdered KOH (14.66 g, 260 mmol)
and MeI (9.72 mL, 153 mmol), and the mix-
ture was stirred at rt overnight. The solution
was diluted with water (25 mL) and extracted
3. Experimental
General methods.—Chemicals were all used
as purchased from the Aldrich Chemical Co.
Solvents were dried and purified, when neces-
sary, by appropriate standard procedures.
Melting points are uncorrected. Optical rota-
tions were measured at 2095 °C (5-cm cell).
TLC was performed on Silica Gel 60 F254 (E.
Merck) with detection by UV light or charring
with H2SO4. Flash-column chromatography
was performed using Silica Gel 60 (230–400
mesh, E. Merck). Elemental analyses were de-
termined in the Microanalysis Laboratories at
the Universidad Complutense de Madrid.
FTIR spectra were obtained from films or
KBr discs. For NMR spectra, chemical shifts
are reported as parts per million down field
from Me4Si. Mass spectra were recorded on a
Micromass AUTOSPECQ mass spectrometer
equipped with a combined EI-CI source, using
methane as ionizing gas. High resolution mass
spectra (HRMS) (EI 70 eV) were obtained
with a resolution of 10,000. Gel-permeation
chromatography (GPC) analyses were carried
with two styragel® HR columns placed in
series, using CHCl3 as solvent at a flow rate of
1 mL/min. Molecular weight studies were de-
termined relative to polystyrene. Intrinsic vis-
cosity measurements were determined in
dichloroacetic acid (DCA) with a semi-micro-
viscosimeter placed in a water bath with the
temperature maintained at 25.090.1 °C.
Calorimetry measurements and thermal treat-
ments were carried out under a nitrogen atmo-
Scheme 6.
Scheme 7. Stereochemical possibilities for the dyads centred
on the arabinaric unit.

M.G. Garc´ıa-Mart´ın et al. / Carbohydrate Research 333 (2001) 95–103
99
Physical constants were identical to those
described.8
with CH2Cl2 (4×50 mL). The combined ex-
tracts were dried (anhyd MgSO4) and concen-
trated to give an oily residue, which was dried
under diminished pressure. The residue was
purified by flash-column chromatography (2:1
ether–hexane) and the title compound was
isolated as a colorless oil (10.8 g, 86.3%): [h]D
+208° (c 1, CH2Cl2); IR (film): w 3030 cm−1
2,3,4-Tri-O-methyl- -xylopyranose (3X).—
D
A solution of 2X (6 g, 20 mmol) in MeOH (90
mL) was hydrogenated as described for 3A to
obtain 3X as an oil (4 g, 98%), which crystal-
lized from ether–hexane. Physical constants
were identical to those described.9,10
1
(Ph). H NMR (CDCl3, 200 MHz): l 7.19–
2,3,4-Tri-O-methyl- -arabinitol (4A).—A
L
7.03 (m, 5 H, OCH2Ph), 4.76 (d, 1 H, J1,2 1.58
Hz, H-1), 4.50 (d, 1 H, J 12.2 Hz, OCH2Ph),
4.35 (d, 1 H, OCH2Ph), 3.55 (dd, 1 H, J4,5 2.2,
J5,5% 12.7 Hz, H-5), 3.40 (m, 4 H, H-2, H-3,
H-4, H-5%), 3.24, 3.21, 3.18 (3s, 9 H, 3 OMe);
13C NMR (50 MHz): l 136.6, 127.5, 127.1,
126.9, 126.7 (OCH2Ph), 95.16 (C-1), 77.5,
76.8, 74.9 (C-2/C-3/C-4), 68.2 (OCH2Ph), 58.0
(C-5), 57.8, 56.7, 56.5 (3 OMe); CIMS: m/z
283 [M+H]+. Anal. Calcd for C15H22O5: C,
63.81; H, 7.85. Found: C, 63.64; H, 7.87.
solution of 3A (7.63 g, 39.7 mmol) in 1:1
MeOH–water (75 mL) was stirred with
NaBH4 (751 mg, 19.8 mmol) for 4 h. The
solution was treated with Dowex 50×8 (H+)
resin, filtered and the filtrate was repeatedly
co-evaporated with MeOH and concentrated
to a pure syrup, which crystallized after treat-
ment with cold ether (5.76 g, 74.8%): mp
61–62 °C; [h]D −2° (c 0.56, CH2Cl2); IR: w
3400 cm−1 (OH); 1H NMR (CDCl3, 200
MHz): l 3.90–3.60 (m, 4 H, H-1, H-1%, H-5,
H-5%), 3.45–3.30 (m, 3 H, H-2, H-3, H-4),
3.48, 3.46, 3.40 (3s, 9 H, 3 OMe); 13C NMR
(50 MHz): l 80.7, 80.5, 80.0 (C-2/C-3/C-4),
60.7, 59.4 (C-1/C-5), 60.4, 58.5, 57.4 (3 OMe);
CIMS: m/z 195 [M+H]+. Anal. Calcd for
C8H18O5: C, 49.47; H, 9.34. Found: C, 49.46;
H, 9.14.
Benzyl 2,3,4-tri-O-methyl-h- -xylopyran-
D
oside (2X).—A solution of 1X7 (10.66 g, 44.0
mmol) in dry Me2SO was treated with MeI
and KOH as described above for 2A and the
mixture was stirred at rt for 24 h. The result-
ing white suspension was treated with water
(30 mL) and 2X was obtained as a white solid.
It was filtered, washed thoroughly with water,
and finally air-dried (12.4 g, quantitative): mp
72–74 °C (from EtOH); [h]D +124.5° (c 0.53,
2,3,4-Tri-O-methyl-xylitol (4X).—It was
prepared from 3X (3.2 g, 16.6 mmol) as de-
scribed for 4A. The oily residue was purified
by flash-column chromatography (first Et2O,
then 10:1 CH2Cl2–MeOH) to give 4X as a
syrup (2.94 g, 90%). IR: w 3400 cm−1 (OH);
1H NMR (CDCl3, 200 MHz): l 3.44, (s, 3 H,
OMe), 3.37 (s, 6 H, 2 OMe), 3.77–3.30 (m,
rest of the protons); 13C NMR (50 MHz): l
80.6 (C-2, C-3, C-4), 62.5 (C-1, C-5), 60.0
(OMe), 57.9 (2 OMe); CIHRMS Calcd for
C8H18O5: 195.1232. Found: 195.1233. Anal.
Calcd for C8H18O5·0.3 H2O: C, 48.13; H, 9.39.
Found: C, 48.17; H, 9.25.
1
CHCl3); IR (KBr): w 3030 cm−1 (Ph). H
NMR (CDCl3, 200 MHz): l 7.30–7.20 (m, 5
H, OCH2Ph), 4.86 (d, 1 H, J1,2 3.6 Hz, H-1),
4.70 (d, 1 H, J 12.2 Hz, OCH2Ph), 4.48 (d, 1
H, OCH2Ph), 3.65 (dd, 1 H, J4,5 5.6, J5,5% 11.0
Hz, H-5), 3.50–3.35 (m, 2 H, H-3, H-5%),
3.25–3.15 (m, 1 H, H-4), 3.10 (dd, 1 H, J2,3
9.4 Hz, H-2), 3.57, 3.42, 3.35 (3s, 9 H, 3
OMe); 13C NMR (50 MHz): l 136.9, 128.2,
127.9, 127.6, (OCH2Ph), 94.5 (C-1), 82.2, 81.3,
79.6 (C-2, C-3, C-4), 68.5 (OCH2Ph), 59.4
(C-5), 60.7, 58.7, 58.3 (3 OMe); CIMS: m/z
175 [M−OBn]+. Anal. Calcd for C15H22O5:
C, 63.81; H, 7.85. Found: C, 63.75; H, 7.84.
2,3,4-Tri-O-methyl-1,5-di-O-tosyl- -arabini-
L
tol (5A).—A cold (0–5 °C) solution of 4A
(100 mg, 0.51 mmol) in dry pyridine (1 mL)
was stirred with tosyl chloride (244 mg, 1.28
mmol) for 2 h. The suspension was diluted
with CH2Cl2 and the solution washed with
water, dried and concentrated to a syrup that
was purified by flash-column chromatography
(3:1 Et2O–hexane). The title compound was
isolated as a syrup (152 mg, 59%), [h]D −10°
2,3,4-Tri-O-methyl- -arabinopyranose (3A).
L
—To a solution of 2A (8.4 g, 29 mmol) in
MeOH (125 mL) was added 10% Pd–C (2.5 g)
and the mixture was treated with H2 (45 psi)
for 24 h at rt. The catalyst was filtered,
washed with MeOH and the filtrate concen-
trated to give 3A as an oil (4.8 g, 84%).

100
M.G. Garc´ıa-Mart´ın et al. / Carbohydrate Research 333 (2001) 95–103
Me–C6H4); 13C NMR (50 MHz), l 144.9,
132.5, 129.8, 127.9 (C6H4), 78.3 (C-3), 77.3
(C-2, C-4), 68.9 (C-1, C-5), 59.6, 58.7 (3
OMe), 21.5 (Me–C6H4). Anal. Calcd for
C22H30O9S2: C, 52.57; H, 6.01; S, 12.76.
Found: C, 52.62; H, 6.12, S, 12.54.
1
(c 0.5, CH2Cl2); H NMR (CDCl3, 200 MHz):
l 7.80 (dd, 4 H, C6H4), 7.30 (dd, 4 H, C6H4),
4.30 (m, 1 H, J4,5 2.4, J5,5% 10.9 Hz, H-5/H-1),
4.10 (m, 3 H, H-5%, H-1/H-5, H-1%), 3.55 (dt, 1
H, J 2.4, J 6.2 Hz, H-3/H-2), 3.40 (m, 1 H,
H-4), 3.20 (m, 1 H, H-2/H-3), 3.32, 3.25, 3.20
(3s, 3 H each, OMe), 2.42 (s, 3 H, Me–C6H4);
13C NMR (50 MHz): l 145.0, 144.9, 132.6,
132.5, 129.9, 127.9 (C6H4), 78.4, 77.9, 78.8
(C-2–C-4), 67.9, 67.4 (C-1/C-5), 60.6, 59.4,
57.6 (3 OMe), 21.6 (Me–C6H4). Anal. Calcd
for C22H30O9S2: C, 52.57; H, 6.01; S, 12.76.
Found: C, 52.30; H, 6.03, S, 12.35.
1,5-Di-O-mesyl-2,3,4-tri-O-methyl-xylitol
(6X).—To a cold (0–5 °C) solution of 4X
(1.06 g, 5.46 mmol) in dry CH2Cl2 (10 mL)
was added triethylamine (1.75 mL, 12.56
mmol), then mesyl chloride (0.96 mL, 12.56
mmol) and the mixture was stirred for 1.5 h at
the same temperature. The mixture was di-
luted with a large excess of CH2Cl2 (200 mL)
and washed successively with a satd solution
of NaHCO3 and brine. The combined extracts
were dried (anhyd MgSO4) and concentrated
to a syrup, which was purified by flash-column
chromatography (Et2O) to give 6X as a color-
less syrup that crystallized on standing in the
1,5-Di-O-mesyl-2,3,4-tri-O-methyl- -arabini-
L
tol (6A).—A cold (0–5 C) solution of 4A (2.5
g, 12.9 mmol) in dry pyridine (10 mL) was
stirred with mesyl chloride (3 mL, 38.6 mmol)
for 1 h. The reaction mixture was diluted with
water (10 mL) and extracted with CH2Cl2
(4×30 mL). The combined extracts were
dried (anhyd MgSO4) and concentrated to
give 6A as a solid (4.16 g, 92%), mp 59–61 °C
(from CH2Cl2–hexane); [h]D −8° (c 0.5,
1
refrigerator (1.49 g, 77.8%); H NMR (CDCl3,
200 MHz): l 4.35 (dd, 2 H, J 4.2, J 10.9 Hz,
H-1, H-5), 4.20 (dd, 2 H, J 6.1, J 10.9 Hz,
H-1%, H-5%), 3.65 (m, 2 H, H-2, H-4), 3.40 (m,
1 H, H-3), 3.41 (s, 3 H, OMe), 3.39 (s, 6 H, 2
OMe), 2.97 (s, 6 H, 2 OMs); 13C NMR (50
MHz): l 78.2 (C-3), 77.6 (C-2, C-4), 68.6 (C-1,
C-5), 59.7, 58.7 (3 OMe), 37.0 (2 OMs);
CIHRMS Calcd for C10H22O9S2: 351.0783.
Found: 351.0776.
CH2Cl2); IR: w 1355 and 1175 cm−1 (SO2); H
1
NMR (CDCl3, 200 MHz): l 4.58 (dd, 1 H, J4,5
2.4, J5,5% 11.4 Hz, H-5), 4.25 (dd, 1 H, J4,5% 3.8
Hz, H-5%), 4.32 (ABX fragment, 2 H, H-1,
H-1%), 3.68 (dt, 1 H, J2,3 2.6, J3,4 6.1 Hz, H-3),
3.53 (m, 1 H, H-4), 3.35 (m, 1 H, H-2), 3.45,
3.43, 3.40 (3s, 3 H each, 3 OMe), 3.02, 3.01
(2s, 6 H, 2 OMs); 13C NMR (50 MHz), l 78.3,
78.1 (C-2–C-4), 67.7, 67.2 (C-1/C-5), 60.7,
59.5, 57.8 (3 OMe), 37.5, 37.3 (2 OMs);
CIMS: m/z 350 [M+H]+. Anal. Calcd for
C10H22O9S2: C, 34.28; H, 6.33; S, 18.30.
Found: C, 33.99; H, 6.38, S, 18.01.
Reaction of 4X with mesyl chloride in dry
pyridine: isolation of 1,4-anhydro-5-O-mesyl-
2,3-di-O-methyl and xylitol (7X and 8X).—A
cold (0–5 °C) solution of 4X (2.65 g, 13.65
mmol) in dry pyridine (10 mL) was stirred
with mesyl chloride (3.17 mL, 40.95 mmol) for
5 h at the same temperature. The reaction was
diluted with water (10 mL) and extracted with
CH2Cl2 (4×30 mL). The combined extracts
were dried (anhyd MgSO4) and concentrated
to a syrup which was purified by flash-column
chromatography (9:1 Et2O–hexane) to give
the racemic mixture of 7X and 8X (1.1 g,
2,3,4-Tri-O-methyl-1,5-di-O-tosyl-xylitol
(5X).—It was prepared from 4X (100 mg, 0.51
mmol) as described for 5A. The reaction mix-
ture was concentrated to dryness and the re-
sulting solid was treated with water (10 mL).
The white solid was filtered, washed with wa-
ter, Et2O, then dried to give 5X (242 mg,
94%), mp 121–123 °C (from EtOAc–hexane);
1
IR: w 1365 and 1180 cm−1 (SO2); H NMR
1
62.8%); [h]D 0° (c 0.5, CH2Cl2). H NMR
(CDCl3, 500 MHz): l 4.37 (dd, 1 H, J4,5 4.3,
J5,5% 10.9 Hz, H-5), 4.28 (dd, 1 H, J4,5% 7.4 Hz,
H-5%), 4.19 (m, 1 H, H-4), 4.02 (dd, 1 H, J1,2
4,6, J1,1% 10 Hz, H-1), 3.84 (dt, 1 H, J 1.5, J 1.7
Hz, H-2), 3.75 (m, 2 H, H-1%, H-3), 3.35, 3.32
(2s, 3 H each, 2 OMe), 2.99 (s, 3 H, OMs); 13C
(CDCl3, 200 MHz): l 7.75 (m, 4 H, C6H4),
7.32 (d, 4 H, C6H4), 4.15 (dd, 2 H, J 4.5, J
10.6 Hz, H-5, H-1), 4.00 (dd, 2 H, J 6.1, J 10.6
Hz H-5%, H-1%), 3.58 (dt, 2 H, J 4.4 Hz, H-2,
H-4), 3.30 (m, 1 H, H-3), 3.28 (s, 6 H, 2
OMe), 3.24, (s, 3 H, OMe), 2.41 (s, 6 H,

M.G. Garc´ıa-Mart´ın et al. / Carbohydrate Research 333 (2001) 95–103
101
(348 mg, 90% from the base), mp (dec.) 268–
270 °C; [h]D −25° (c 0.5, water); IR: w 2936
cm−1 (NH+3 ); 1H NMR (Me2SO-d6, 200
MHz): l 8.27 (bs, 4 H, 2 NH2), 3.70–3.60 (m,
3 H, H-2, H-3, H-4), 3.40, 3.39, 3.35 (3s, 9 H,
3 OMe), 3.00–2.75 (m, 4 H, H-1, H-1%, H-5,
NMR (125 MHz): l 83.8 (C-3), 83.1 (C-2),
77.9 (C-4), 71.1 (C-1), 68.4 (C-5), 57.7, 56.9 (2
OMe), 37.4 (OMs); CIMS: m/z 241 [M+H]+.
Anal. Calcd for C8H16O6S: C, 39.65; H, 6.75;
S, 13.00. Found: C, 39.99; H, 6.71, S, 13.34.
CH2Cl2
13
H-5%); C NMR (50 MHz): l 78.8, 77.9, 77.7
1,5-Diazido-1,5-dideoxy-2,3,4-tri-O-methyl-
(C-2, C-3, C-4), 59.7, 58.8, 57.6 (3 OMe), 39.1
(C-1, C-5). CIMS: m/z 193 [M+H]+. Anal.
Calcd for C8H22Cl2N2O3: C, 36.24; H, 8.36; N,
10.56. Found: C, 36.56; H, 8.22, N, 10.24.
1,5-Diamino-1,5-dideoxy-2,3,4-tri-O-methyl-
xylitol dihydrochloride (10X).—It was pre-
pared from 9X (0.6 g, 2.47 mmol) as described
for 10A. The hydrochloride 10X was obtained
as a solid, which was filtered and washed with
EtOAc (0.6 g, 92%), mp 103–106 °C; IR: w
L
-arabinitol (9A).—To a solution of 6A (3.95
g, 11.3 mmol) in dry DMF (25 mL) was added
NaN3 (1.88 g, 29.3 mmol) and the suspension
was stirred at 70 °C for 24 h. The reaction
mixture was diluted with acetone and filtered
through diatomaceous earth. The solids were
washed with CH2Cl2 and the combined ex-
tracts and the organic solution were concen-
trated to a residue. Flash-column chromato-
graphy (1:1 Et2O-hexane) of the residue gave
9A as a yellowish liquid (2.49 g, 90%); [h]D
−65.5° (c 0.6, CH2Cl2); IR: w 2100 cm−1 (N3);
1H NMR (CDCl3, 200 MHz): l 3.70–3.24 (m,
7 H), 3.46, 3.44, 3.42 (3s, 9 H, 3 OMe); 13C
NMR (50 MHz), l 75.5, 79.3 (C-2, C-3, C-4),
60.9, 59.2, 57.5 (3 OMe), 50.8, 49.4 (C-1, C-5);
CIHRMS Calcd for C8H16O3N6: 245.1352.
Found: 245.1369.
1
2936 cm−1 (NH+3 ); H NMR (DMSO-d6, 200
MHz): l 8.2 (bs, 4 H, 2 NH2), 3.65 (m, 3 H,
H-2, H-3, H-4), 3.40 (s, 3 H, OMe), 3.37 (s, 6
H, 2 OMe), 3.00–2.80 (m, 4 H, H-1, H-1%,
13
H-5, H-5%); C NMR (50 MHz): l 79.1 (C-3),
76.2 (C-2, C-4), 59.0, 58.4 (3 OMe), 39.1 (C-1,
C-5). Anal. Calcd for C8H22Cl2N2O3·0.3 H2O:
C, 35.50; H, 8.41; N, 10.34. Found: C, 35.60;
H, 8.49, N, 10.05.
1,5-Diazido-1,5-dideoxy-2,3,4-tri-O-methyl-
xylitol (9X).—It was obtained from 6X (1.48
g, 4.2 mmol) as described for 9A. Flash-
column chromatography (1:1 Et2O–hexane)
of the residue gave 9X as a yellowish liquid
2,3,4-Tri-O-methyl- -arabinaric acid (11A).
L
—To a solution of 3A (5.1 g, 26.6 mmol) in
water (5 mL) was added nitric acid (60%, 10
mL) and the mixture was heated at 70–80 °C
with stirring for 24 h. The reaction was diluted
with water (200 mL) and the residue co-evap-
orated several times with water and finally
with toluene. Flash-column chromatography
(20:1 CH2Cl2–MeOH) of the residue afforded
the title compound as a syrup that crystallized
on standing (5.7 g, 97%), mp 88–89 °C; [h]D
+32° (c 1, CH2Cl2); IR: w 1730 cm−1 (CO);
1H NMR (CDCl3, 200 MHz): l 9.17 (bs, 2 H,
COOH), 4.03–3.91 (m, 3 H, H-2, H-3, H-4),
3.45, 3.40, 3.36 (3s, 9 H, 3 OMe); 13C NMR
(50 MHz): l 175.0, 174.9 (C-1, C-5), 81.5,
79.0, 78.9 (C-2, C-3, C-4), 60.3, 59.4, 58.6 (3
OMe). CIMS: m/z 223 [M+H]+. Anal. Calcd
for C8H14O7: C, 43.24; H, 6.35. Found: C,
42.99; H, 6.53.
1
(0.6 g, 58%). IR: 2100 cm−1 (N3); H NMR
(CDCl3, 200 MHz): l 3.48 (OMe), 3.43 (2
OMe), 3.50–3.33 (rest of the protons); 13C
NMR (50 MHz): l 79.6 (C-3), 79.5 (C-2, C-4),
60.3, 58.5 (3 OMe), 50.7 (C-1, C-5); CIHRMS
Calcd for C8H16O3N6: 245.1362. Found:
245.1371.
1,5-Diamino-1,5-dideoxy-2,3,4-tri-O-methyl-
-arabinitol dihydrochloride (10A).—To a so-
L
lution of 9A (356 mg, 1.46 mmol) in dry THF
(8 mL) was added 1 M LiAlH4 in THF (8.76
mL) under Ar and the mixture was stirred for
2 h. A satd sodium sulfate solution was added
and the suspension was filtered through di-
atomaceous earth. The solid was washed with
THF (60 mL) and the filtrate concentrated to
a syrup, which was dried under diminished
pressure. This syrup was treated with a 10%
solution of HCl in EtOAc (15 mL), and the
hydrochloride 10A was obtained as a solid,
which was filtered and washed with EtOAc
2,3,4-Tri-O-methyl-xylaric acid (11X).—It
was prepared from 3X (4.0 g, 20.8 mmol) as
described for 11A. Flash-column chromatog-
raphy (20:1 CH2Cl2–MeOH) of the residue
afforded the title compound as a syrup (4.7 g,
1
quant.). IR: w 1730 cm−1 (CO); H NMR

102
M.G. Garc´ıa-Mart´ın et al. / Carbohydrate Research 333 (2001) 95–103
mmol) were added and the mixture was stirred
at 45 °C for 4 days. The reaction mixture was
diluted with acetone (6 mL) and added drop-
wise to Et2O (200 mL) with stirring. The
precipitated white solid was filtered and
washed with ether and dried under diminished
pressure at 40 °C, to obtain 14 (167 mg, 77%),
Tm 250 °C (DH=39.5 J/g); [h]D +31° (c 0.52,
CH2Cl2); [p] 0.4 dL/g; Mw 27500, Mw/Mn 1.4;
IR: w 1677 (amide I), 1528 cm−1 (amide II);
13C NMR (CDCl3, 50 MHz): l 170.6, 170.4,
170.3 (CO), 82.1, 81.9, 81.7, 81.6, 81.5, 81.1,
79.3, 79.0, 77.0 (CH, main chain), 60.8, 60.7,
59.6, 59.5, 58.8, 58.7, 58.3, 58.2, 57.4 (OMe),
39.2, 37.8 (CH2, main chain). Anal. Calcd for
C16H30O8N2·0.5 H2O: C, 49.60; H, 8.06; N,
7.23. Found: C, 49.47; H, 8.30; N, 7.31.
(CDCl3, 200 MHz): l 9.00 (bs, 2 H, COOH),
4.05–3.93 (m, 3 H, H-2, H-3, H-4), 3.49, 3.44,
(2s, 9 H, 3 OMe); 13C NMR (50 MHz): l
174.5 (C-1, C-5), 81.6 (C-3), 78.5 (C-2, C-4),
60.2, 59.4 (3 OMe). CIHRMS Calcd for
C8H14O7: 223.0817. Found: 223.0818.
Pentachlorophenyl 2,3,4-tri-O-methyl- -ara-
L
binarate (13A).—To a cold (0–5 °C) solution
of 11A (1.03 g, 4.67 mmol) in dry CH2Cl2 (12
mL) were added pentachlorophenol (2.48 g,
9.34 mmol), N,N-dicyclohexylcarbodiimide
(2.48 g, 9.34 mmol) and N,N-dimethy-
laminopyridine (15 mg). The mixture was
stirred at rt overnight, then diluted with
CH2Cl2 (50 mL) and the dicyclohexylurea
formed was filtered through diatomaceous
earth. The filtrate was washed with 5% aq
solution of AcOH, then with water, dried
(anhyd MgSO4) and concentrated to a residue.
Flash-column chromatography (1:5 Et2O–
petroleum ether) of this residue afforded 15A
as a solid (2.37 g, 71%), mp 137–139 °C; [h]D
+39° (c 0.5, CH2Cl2); IR: w 1780 cm−1 (CO);
1H NMR (CDCl3, 200 MHz): l 4.5 (d, 1 H, J
1.8 Hz, H-2/H-4), 4.35 (m, 2 H, H-3, and
H-2/H-4), 3.68, 3.67, 3.51 (3s, 9 H, 3 OMe).
13C NMR (50 MHz), l 167.4, 167 (C-1, C-5),
143.7, 132.2, 132.0, 127.3 (C6Cl5), 80.6 (C-3),
79.0 (C-2, C-4), 60.7, 60.0, 59.6 (3 OMe).
Anal. Calcd for C20H12Cl10O7: C, 33.42; H,
1.68. Found: C, 33.71; H, 1.84.
Acknowledgements
We thank the C.I.C.Y.T. (Comisio´n Inter-
ministerial de Ciencia y Tecnolog´ıa) of Spain
for financial support (Grant MAT99-0578-
C02-01).
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