The direct synthesis of 6-amino-6-deoxyaldonic acids as monomers for the preparation of polyhydroxylated nylon 6

Article abstract of DOI:10.1016/j.tetasy.2006.04.018

6-Azido-6-deoxy-d-galactitol and d-mannitol were obtained quantitatively via the reduction of the corresponding 6-azido-6-deoxy-d-hexono-1,4-lactones, and 6-azido-6-deoxy-d-glucitol was obtained by the reduction of 6-azido-6-deoxyglucose in good yields. The reduction of monoazidodeoxyhexitols by catalytic hydrogenation gave the monoaminohexitol analogues in 95-98% yields. Oxidation of these afforded the corresponding 6-amino-6-deoxy-d-aldonic acids in moderate yields. Alternatively, saponification of 6-azido-6-deoxy-d-hexonolactones gave 6-azido-6-deoxyaldonic acid salts which, after reduction followed by neutralization, led to the expected compounds in 82-88% overall yields.

Full text of DOI:10.1016/j.tetasy.2006.04.018

Tetrahedron: Asymmetry 17 (2006) 1349–1354
The direct synthesis of 6-amino-6-deoxyaldonic acids as
monomers for the preparation of polyhydroxylated nylon 6
*
`
Ludovic Chaveriat, Imane Stasik, Gilles Demailly and Daniel Beaupere
Laboratoire des Glucides, UMR 6219, Universite´ de Picardie Jules Verne, 33 Rue Saint-Leu, 80039 Amiens, France
Received 3 March 2006; accepted 18 April 2006
Abstract—6-Azido-6-deoxy-D-galactitol and D-mannitol were obtained quantitatively via the reduction of the corresponding 6-azido-6-
deoxy-D-hexono-1,4-lactones, and 6-azido-6-deoxy-D-glucitol was obtained by the reduction of 6-azido-6-deoxyglucose in good yields.
The reduction of monoazidodeoxyhexitols by catalytic hydrogenation gave the monoaminohexitol analogues in 95–98% yields. Oxida-
tion of these afforded the corresponding 6-amino-6-deoxy-D-aldonic acids in moderate yields. Alternatively, saponification of 6-azido-6-
deoxy-D-hexonolactones gave 6-azido-6-deoxyaldonic acid salts which, after reduction followed by neutralization, led to the expected
compounds in 82–88% overall yields.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
In contrast, polyhydroxylated nylon 6,6 has been exten-
sively studied.3,7 This is due, undoubtedly, to the difficulty
in accessing polyhydroxylated 6-aminohexanoic acid
monomers, which require longer synthetic sequences.2
In recent years, efforts have been made to synthesize poly-
mers that are more hydrophilic and degradable.1 The
majority of commercially available synthetic biodegradable
polymers have been limited to polyesters.2
2. Results and discussion
The synthesis of polyamides that are more hydro-
philic and degradable than industrial nylons has
attracted considerable attention.3 This biodegradability
of polyamides has found many applications, such as
biomedical materials for temporary surgical use and in
drug delivery.4
Herein, we report a direct and efficient synthesis of fully
hydroxylated 6-amino-6-deoxyaldonic acids from unpro-
tected D-hexonolactones and D-glucose as starting materi-
als either via 6-amino-6-deoxy-D-hexitols (pathway A,
Scheme 1) or via 6-amino-6-deoxy-D-aldonic acid salts
(pathway B, Scheme 1).
Apart from the work of Fleet2,5 and Varela,1b,6 there have
been no reports on the synthesis of polymeric sugar ana-
logues of polyhydroxylated nylon 6.
The obtained 6-amino-6-deoxyaldonic acids should
provide monomers for polymerization to afford fully
OH
OH
HO
HOH2C
OH
O
O
H2N
OH
OH
or
O
HO
HO
HO
OH
OH
OH
OH
OH
OH
H2N
OH
HO OH
O
OH
OH
N3
COO-Na+
OH
OH
Scheme 1.
*
Corresponding author. Tel.: +33 3 22 82 75 66; fax: +33 3 22 82 75 60; e-mail: imane.Stasik@sc.u-picardie.fr
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.04.018

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L. Chaveriat et al. / Tetrahedron: Asymmetry 17 (2006) 1349–1354
afforded 6-azido-6-deoxy-D
-mannono-1,4-lactone
6
in
OH
OH
OH
OH
98% yield. Treatment of 6 with sodium borohydride pro-
duced 6-azido-6-deoxy-D-mannitol 7 in 98% isolated yield.
Catalytic hydrogenation of 7 gave 6-amino-6-deoxy-D-
mannitol 8 in 98% isolated yield9 (Scheme 4).
OH
H2N
N
H
O
n
O
OH
OH
OH
OH
A
For the synthesis of 6-amino-6-deoxy-D-glucitol 12, we first
selected D-gluconolactone as a starting material. D-Gluc-
ono-1,5-lactone was subjected to bromination, for the prep-
aration of 6-bromo-6-deoxy-D-glucono-1,4-lactone, by
using carbon tetrabromide–triphenylphosphine system.
However, in all instances and under different reaction condi-
tions, the bromination was unsuccessful. The NMR spectra
of the resulting product showed the formation of 3,6-anhy-
dro-D-glucono-1,4-lactone. This cyclization suggested the
attack of the alkoxyphosphonium group at C-3–C-6, with
nucleophilic displacement of the bromide atom. Tosylation
of D-glucono-1,5-lactone afforded the same compound.
Scheme 2.
hydroxylated polymers of nylon 6, such as species A
(Scheme 2).
The preceding paper described the synthesis of 5-amino-
deoxypentitols from unprotected D-pentono-1,4-lactones
in 84–92% overall yields.8 In pathway A, we applied this
strategy for the synthesis of 6-amino-6-deoxy-D-hexitols.
We have previously described the preparation of 6-bromo-
6-deoxy-D-galactono-1,4-lactone 1 from the unprotected
corresponding D-galactono-1,4-lactone in good yield
(82%), by means of carbon tetrabromide–triphenylphos-
phine in pyridine.9
The SOBr2/DMF system which, with the pentonolactones,
regioselectively gives, the 5-bromo derivatives10 led in this
case to a complex mixture. In a second reaction time, bro-
mination of D-gluconolactone using 32% HBr in acetic
acid,11 afforded a mixture of 6-bromo-6-deoxy-D-glucono-
1,4-lactone and 2,6-dibromo derivative.
Thus treatment of 1 with lithium azide in N,N-dimethyl-
formamide gave 6-azido-6-deoxy-D-galactono-1,4-lactone
2 in 91% yield. Compound 2 was then treated with sodium
borohydride in EtOH (The pH was maintained below 7.) to
give 6-azido-6-deoxy-D-galactitol 3 in 98% yield. Catalytic
hydrogenation of 3 over palladium on charcoal (10%), at
50 ꢁC in EtOH, produced the desired 6-amino-6-deoxy-D-
galactitol 4 in 98% yield9 (Scheme 3).
Due to the difficulties in obtaining 6-bromo-6-deoxy-D-
glucono-1,4-lactone, we tried an alternative synthetic path-
way for the preparation of 6-amino-6-deoxy-D-glucitol 12
starting from D-glucose (Scheme 5). Treatment of D-glu-
cose with carbon tetrabromide–triphenylphosphine in
DMF gave 6-bromo-6-deoxy-D-glucose 9 in 56% yield (9
should be employed crudely for the next step). The nucleo-
philic substitution of the bromide in compound 9 with lith-
ium azide readily took place and gave the expected azide
derivative 10 in 70% yield. Product 10 was accompanied,
under different reaction conditions, by the presence of a
by-product, which was identified as 3,6-anhydro-D-glucose.
When 10 was treated by sodium borohydride in ethanol,
6-azido-6-deoxy-D-glucitol 11 was isolated in 96% yield.
Catalytic hydrogenation of 11 gave 6-amino-6-deoxy-D-
glucitol 12 in 95% yield.
D-Mannono-1,4-lactone was used as the key starting mate-
rial for the synthesis of 6-amino-6-deoxy-D-mannitol 8. For
the synthesis of D-mannono-1,4-lactone, which was not
commercially available, we oxidized D-mannose, using a
modified procedure, and obtained the title product, which
was isolated in quantitative yield (bromine-water in the
presence of sodium hydrogencarbonate).9
Bromination of D-mannono-1,4-lactone using a PPh3/CBr4
system in pyridine, followed by azidation (LiN3/DMF),
OH
OH
OH
HO
HO
OH
O
N3
O
Br
b)
a)
c)
OH
OH
O
O
N3
H2N
H
H
OH
OH
OH
OH
HO
OH
HO
OH
3
4
1
2
Scheme 3. Reagents and conditions: (a) LiN3–DMF, 91%; (b) NaBH4–EtOH, 98%; (c) H2–Pd/C, 98%.
OH
H
OH
OH
OH
OH
OH
Br
N3
O
O
a)
c)
b)
O
OH
O
OH
H2N
N3
H
OH
OH
OH
OH
HO
OH
HO
OH
5
7
6
8
Scheme 4. Reagents and conditions: (a) LiN3–DMF, 98%; (b) NaBH4–EtOH, 98%; (c) H2–Pd/C, 98%.

L. Chaveriat et al. / Tetrahedron: Asymmetry 17 (2006) 1349–1354
1351
Br
HO
N3
OH
OH
OH
OH
O
O
O
a)
c)
b)
OH
d)
OH
HO
OH
OH
HO
HO
HO
OH
H2N
N3
OH
OH
OH
OH
12
HO
OH
HO
OH
OH
9
10
11
Scheme 5. Reagents and conditions: (a) PPh3–CBr4, DMF, 56%; (b) LiN3–DMF, 70%; (c) NaBH4–EtOH, 96%; (d) H2–Pd/C, 95%.
For the oxidation of 6-amino-6-deoxy-D-hexitols to 6-ami-
no-6-deoxy-D-glyconic acids, we proceeded using the same
method with compound 4. Thus, an aqueous solution of 6-
amino-6-deoxy-D-galactitol 4 was treated with TEMPO
(2,2,6,6-tetramethyl-1-piperidinyloxy) in the presence of
sodium hypochlorite and potassium bromide.12 After
4 days, as evolution was no longer noted, and the reaction
was stopped. NMR spectra of the crude material showed
the presence of the starting material 4 and the formation
of a second product. This later presents, in particular, in
addition to the signal at 43 ppm (corresponding to the ami-
nomethylene group) a signal at 178 ppm corresponding to
a carbonyl group. The mass spectrum showed a diagnostic
peak at m/z 218 (M+Na)+, which confirms the formation
of the 6-amino-6-deoxy-D-galactonic acid. In the non-resol-
uble mixture (by liquid chromatography and HPLC) of
6-amino-6-deoxy-D-galactonic acid 14 and compound 4,
the ratio was 4:14 = 3:2.
Using this strategy, 6-azido-6-deoxy-D-mannono-1,4-lac-
tone 6 and 6-azido-6-deoxy-D-glucono-1,5-lactone 17 were
treated using the same conditions to give 6-amino-6-deoxy-
D-mannonic acid 16 and 6-amino-6-deoxy-D-gluconic acid
(19) in 88% and 85% yields, respectively.
3. Conclusion
In summary, we have reported a new procedure for the
synthesis of 6-amino-6-deoxy-D-galactitol (4), D-mannitol
(8) and D-glucitol (12) in good yields. We have also devel-
oped a direct synthesis of 6-amino-6-deoxy-D-galactonic
acid (14), 6-amino-6-deoxy-D-mannonic acid (16) and 6-
amino-6-deoxy-D-gluconic acid (19), which may be suitable
monomers for the preparation of new polymers as poly-
hydroxylated nylon 6.
To avoid this difficult step of separation, we investigated a
second route (pathway B). Treatment of 6-azido-6-deoxy-
4. Experimental
4.1. General
D-galactono-1,4-lactone
2 with NaOH (2 equiv), in
EtOH/water at room temperature for 1 h, allowed us to
obtain 6-azido-6-deoxy-D-galactonic acid salt 13 in 95%
yield (Scheme 6). Catalytic hydrogenation (Pd/C 10%) of
13, in water at room temperature for 1 h, followed by treat-
ment with acidic resin (Amberlite IR-120+) afforded, after
filtration, 6-amino-6-deoxy-D-galactonic acid 14 in 93%
yield (Scheme 6).
Melting points were determined on a Buchi 535 apparatus
and are uncorrected. Optical rotations were measured with
a JASCO DIP-370 digital polarimeter, using a sodium
lamp (k = 589 nm) at 24 ꢁC. 1H and 13C NMR spectra were
recorded in D2O, in MeOD or in DMSO-d6. Me4Si
was used as an internal standard on a Bruker 300 MHz
OH
HO
OH
HO
OH
O
N3
O-Na+
c)
b)
OH
O
N3
H2N
HO
HO
OH
95%
93%
O
OH
13
OH
O
OH
OH
OH
14
OH
2
OH
OH
OH
c)
b)
O
N3
O-Na+
OH
O
N3
H2N
93%
92%
HO
HO
OH
O
OH
OH
15
OH
16
O
OH
6
N3
N3
OH
OH
OH
OH
O
O
a)
66%
O-Na+
OH
b)
c)
HO
OH
H2N
HO
HO
O
N3
90%
91%
OH
OH
O
OH
OH
O
HO
OH
OH
10
17
18
19
Scheme 6. Reagents and conditions: (a) Br2, NaHCO3, H2O; (b) NaOH, EtOH–H2O, rt; (c) H2, Pd/C, H2O; Amberlite IR-120+.

1352
L. Chaveriat et al. / Tetrahedron: Asymmetry 17 (2006) 1349–1354
spectrometer. Thin-layer chromatography (TLC) was per-
formed on E. Merck glass plates coated with silica gel
sheets (Silica Gel F254) and stained with phosphomolybdic
acid–aqueous H2SO4 solution. Column chromatography
was carried out on silica gel (E. Merck 230–400 mesh).
All solvents were distilled before use.
4.1.3.2. 6-Azido-6-deoxy-D-mannitol 7. White solid
(0.46 g, 98%): Rf 0.61 (EtOAc–MeOH 7:3); [a]D = +27 (c
1.00, H2O); mp 119–120 ꢁC; 1H NMR (300 MHz, MeOD):
d 3.85 (m, 4H), 3.70 (m, 2H), 3.57 (dd, 1H, J = 6.4,
12.9 Hz), 3.41 (dd, 1H, J = 2.6 Hz). 13C NMR (75 MHz,
MeOD): d 71.7, 70.6, 70.2, 69.5, 63.8, 54.7; LC–MS
(m/z): 230 (M+Na)+. Anal. Calcd for C6H13N3O5: C,
34.78; H, 6.32; N, 20.28. Found: C, 34.81; H, 6.35; N, 20.25.
4.1.1. 6-Bromo-6-deoxy-D-glucose 9. A solution of D-glu-
cose (1 g, 5.55 mM) in DMF (50 mL) was treated with tri-
phenylphosphine (2.91 g, 2 equiv) and carbon tetrabromide
(3.68 g, 2 equiv) at 20 min intervals. The mixture was stir-
red, under an inert atmosphere, at 50 ꢁC, for 1.5 h. The
solution was concentrated in vacuo, the residue was diluted
with water and washed with CH2Cl2. The water extracts
were concentrated in vacuo and the obtained residue chro-
matographed on silica gel. Elution with CH2Cl2–MeOH
(9:1) gave 9 (0.75 g, 56%) as a white solid; (a/b = 1); Rf
0.4 (EtOAc–MeOH 9:1; 13C NMR (75 MHz, MeOD): d
99.2, 96.3, 76.2, 75.2, 75.0, 73.4, 72.3, 70.6, 34.0, 33.2;
LC–MS (m/z): 266 (M+Na)+. Anal. Calcd for C6H11BrO5:
C, 29.65; H, 4.56; Br, 32.88. Found: C, 29.60; H, 4.59; Br,
32.83.
4.1.3.3. 6-Azido-6-deoxy-D-glucitol 11. White solid
(0.282 g, 96%): Rf 0.56 (EtOAc–MeOH 7:3); mp 187–
1
188 ꢁC; [a]D = +12.2 (c 0.50, H2O); H NMR (300 MHz,
D2O): d 4.06 (m, 1H), 3.76 (dd, 1H, J = 4.5, 8.2 Hz), 3.42
(m, 3H), 3.27 (dd, 1H, J = 7.0, 12.6 Hz), 3.21 (dd, 1H,
J = 4.4 Hz); 13C NMR (75 MHz, D2O): d 73.0, 71.9,
71.2, 69.7, 63.4, 54.5; LC–MS (m/z): 230 (M+Na)+. Anal.
Calcd for C6H13N3O5: C, 34.78; H, 6.32; N, 20.28. Found:
C, 34.73; H, 6.29; N, 20.32.
4.1.4. General procedure for the reduction of 6-azido-6-
deoxy-D-galactitol, D-mannitol and D-glucitol by catalytic
hydrogenation. A solution of 6-azido-6-deoxy-D-galactitol
3, D-mannitol 7, or D-glucitol 11 (0.2 g, 0.97 mM) in EtOH
(8 mL) was treated with palladium on charcoal (10%,
0.035 g) and then hydrogenated, for 2 h, at 50 ꢁC. The
mixture was filtered through a layer of Celite and the
filtrate was concentrated in vacuo to give the desired
monoaminoalditol.
4.1.2. 6-Azido-6-deoxy-D-glucose 10. A stirred solution of
6-bromo-6-deoxy-D-glucose 9 (0.4 g, 1.65 mM) in DMF
(5 mL) was treated with lithium azide (20% in H2O)
(6 mL, 1.3 equiv) and set aside at 80 ꢁC for 1 h. The
mixture was poured into ice-water (7 mL) and the product
extracted with ethyl acetate. The organic layer was concen-
trated in vacuo and the obtained residue was chromato-
graphed on silica gel. Elution with EtOAc–hexanes (7:3)
gave 10 (0.243 g, 70%) as a yellow oil: Rf 0.4 (EtOAc–
MeOH 9:1; 13C NMR (75 MHz, MeOD): d 97.0, 92.9,
76.7, 75.4, 75.1, 73.6, 72.6, 71.5, 71.2, 71.0, 51.6; LC–MS
(m/z): 228 (M+Na)+. Anal. Calcd for C6H11N3O5: C,
35.12; H, 5.40; N, 20.48. Found: C, 35.08; H, 5.43; N,
20.45.
4.1.4.1. 6-Amino-6-deoxy-D-galactitol 4. White solid
(0.171 g, 98%): Rf 0.31 (EtOAc–MeOH 5:5); [a]D = +22
(c 0.80, H2O); mp 157–158 ꢁC; 1H NMR (300 MHz,
D2O): d 3.92 (m, 3H), 3.31 (m, 2H), 2.63 (d, 2H); 13C
NMR (75 MHz, D2O): d 71.9, 71.1, 63.8, 63.6, 43.9; LC–
MS (m/z): 204 (M+Na)+. Anal. Calcd for C6H15O5N: C,
39.77; H, 8.34; N, 7.73. Found: C, 39.73; H, 8.30; N, 7.69.
4.1.4.2. 6-Amino-6-deoxy-D-mannitol 8. White solid
(0.168 g, 98%): Rf 0.25 (EtOAc–MeOH 5:5); [a]D = +28.4
(c 1, H2O); mp 149–151 ꢁC; H NMR (300 MHz, D2O): d
3.79 (dd, 1H, J = 2.3, 11.5 Hz), 3.65 (m, 4H), 3.57
(dd,1H, J = 7.1 Hz). 2.94 (dd, 1H, J = 2.8, 14.8 Hz), 2.63
(dd, 1H, J = 7.6 Hz); 13C NMR (75 MHz, D2O): d 71.2,
71.0, 69.6, 63.6, 43.7; LC–MS (m/z): 204 (M+Na)+. Anal.
Calcd for C6H15O5N: C, 39.77; H, 8.34; N, 7.73. Found: C,
39.70; H, 8.37; N, 7.69.
4.1.3. General procedure for the reduction of 6-azido-6-
deoxy derivatives. To a solution of 6-azido-6-deoxy-D-
hexono-1,4-lactones 2, 6 (0.56–0.46 g) or 6-azido-6-deoxy-
D-glucose 10 (0.29 g) in EtOH (20 mL) was added
NaBH4 (8 mM) at such a rate that the pH was maintained
below 7. Then a further amount of NaBH4 (9.5 mM) was
added to increase the pH to 9. Stirring was continued
at room temperature, for 1 h, before adding more ion
exchange resin (Dowex 50 · 8–100 ion) to decrease the
pH to 3. The resin was then removed by filtration. The fil-
trate was concentrated and co-concentrated with MeOH
(3 · 18 mL) to give the crude mixture, which was chro-
matographed on silica gel; elution was done with EtOAc–
MeOH (1:1).
1
4.1.4.3. 6-Amino-6-deoxy-D-glucitol 12. White solid
(0.166 g, 95%): Rf 0.32 (EtOAc–MeOH 5:5); [a]D = +4.2
1
(c 1, H2O); mp 179–180 ꢁC; H NMR (300 MHz, D2O): d
3.90 (m, 1H), 3.63 (m, 5H), 3.02 (dd, 1H, J = 6.7,
12.2 Hz) , 2.28 (dd, 1H); 13C NMR (75 MHz, D2O): d
71.3, 70.6, 69.9, 67.2, 64.1, 44.9; LC–MS (m/z): 204
(M+Na)+. Anal. Calcd for C6H15O5N: C, 39.77; H, 8.34;
N, 7.73. Found: C, 39.73; H, 8.30; N, 7.68.
4.1.3.1. 6-Azido-6-deoxy-D-galactitol 3. White solid
(0.56 g, 98%): Rf 0.65 (EtOAc–MeOH 7:3); [a]D = À15.4
(c 0.50, DMSO); mp 141–142 ꢁC; 1H NMR (300 MHz,
DMSO-d6): d 3.87 (m, 1H), 3.69 (dd, 1H, J = 4.6,
12.3 Hz), 3.40 (m, 4H), 3.17 (dd, 1H, J = 4.6, 12.3 Hz).
13C NMR (75 MHz, DMSO-d6): d 70.9, 70.7, 70.0, 63.9,
54.9; LC–MS (m/z): 230 (M+Na)+. Anal. Calcd for
C6H13N3O5: C, 34.78; H, 6.32; N, 20.28. Found: C,
34.75; H, 6.36; N, 20.33.
4.1.5. 6-Azido-6-deoxy-D-glucono-1,5-lactone 17. To a
solution of 6-azido-6-deoxy-D-glucose 10 (0.77 g, 3.76
mM) and sodium hydrogencarbonate (1.12 g, 1.5 equiv)
in distilled water (10 mL) cooled at 0 ꢁC, bromine
(3 · 0.07 mL, 1.5 equiv) was added at 20 min intervals.

L. Chaveriat et al. / Tetrahedron: Asymmetry 17 (2006) 1349–1354
1353
The reaction mixture was stirred at this temperature for 1 h
and then for 3 h at room temperature. Sodium thiosulfate
was added to destroy the excess of bromine, and the sol-
vent was removed in vacuo to give a white solid. The solid
obtained was extracted with acetone at 50 ꢁC. The mixture
was filtered through a layer of Celite and the filtrate con-
centrated in vacuo to give 17 (0.5 g, 66%) as a yellow oil:
resin (Amberlite IR-120+) was added and the suspension
stirred for 30 min. The resin was then removed by filtra-
tion. The filtrate was concentrated in vacuo to give the
desired 6-amino-6-deoxy-D-glyconic acid.
4.1.7.1. 6-Amino-6-deoxy-D-galactonic acid 14. White
solid (0.375 g, 93%): [a]D = +83.2 (c 0.4, H2O); mp 202–
203 ꢁC; 1H NMR (300 MHz, D2O): d 4.27 (d, 1H,
J = 1.5 Hz), 4.04 (m, 1H), 3.88 (dd, 1H, J = 9.5 Hz), 3.49
(dd, 1H, J = 1.6 Hz), 3.06 (d, 2H, J = 6.2 Hz); 13C NMR
(75 MHz, D2O): d 178.4, 71.4, 71.1, 70.8, 66.5, 43.0; LC–
MS (m/z): 218 (M+Na)+. Anal. Calcd for C6H13NO6: C,
36.92; H, 6.72; N, 7.18. Found: C, 36.88; H, 6.76; N, 7.21.
1
Rf 6 (EtOAc–MeOH 6:1); [a]D = +79 (c 0.5, MeOH); H
NMR (300 MHz, MeOD): d 4.08 (d, 1H), 4.0 (d, 1H,
J = 9.3 Hz), 3.82 (dd, 1H, J = 7.5 Hz), 3.72 (t, 1H,
J = 9.1 Hz), 3.15 (dd, 1H, J = 2.6, 14.4 Hz), 2.97 (dd,
1H, J = 4.0 Hz); 13C NMR (75 MHz, MeOD): d 173.2,
78.1, 74.5,72.8, 71.6, 53.4; LC–MS (m/z): 226 (M+Na)+.
Anal. Calcd for C6H9N3O5: C, 35.47; H, 4.47. N, 20.68.
Found: C, 35.40; H, 4.42; N, 20.71.
4.1.7.2. 6-Amino-6-deoxy-D-mannonic acid 16. White
solid (0.371 g, 92%): [a]D = +4.3 (c 0.6, H2O); mp 199–
201 ꢁC; 1H NMR (300 MHz, D2O): d 4.04 (d, 1H,
J = 5.7 Hz), 3.89 (dd, 1H, J = 1.6 Hz), 3.84 (m, 1H,),
3.66 (dd, 1H, J = 8.1 Hz), 3.29 (dd, 1H, J = 3.3,
13.2 Hz), 2.97 (dd, 1H, J = 8.6 Hz); 13C NMR (75 MHz,
D2O): d 179.4, 74.0, 72.5, 70.7, 67.6, 42.7; LC–MS (m/z):
218 (M+Na)+. Anal. Calcd for C6H13NO6: C, 36.92; H,
6.72; N, 7.18. Found: C, 36.95; H, 6.69; N, 7.13.
4.1.6. General procedure for preparation of 6-azido-6-deoxy-
D-aldonic acid sodium salts. To a solution of 6-azido-
6-deoxy-D-hexonolactone 2, 6 or 17 (1 g, 4.92 mM) in
EtOH/water (3:1, 10 mL) was added NaOH (2 equiv).
The reaction mixture was stirred at room temperature for
1 h 30 min and EtOH (10 mL) was added. The suspension
was then filtered, and the white solid obtained was washed
with EtOH/water (3:1, 10 mL) to give the desired 6-azido-
6-deoxy-D-glyconic acid salt.
4.1.7.3. 6-Amino-6-deoxy-D-gluconic acid 19. White
solid (0.367 g, 91%): [a]D = +18.7 (c 0.5, H2O); mp 199–
201 ꢁC; 1H NMR (300 MHz, D2O): d 3.61 (d, 1H,
J = 5.1 Hz), 3.43 (dd, 1H, J = 2.0 Hz), 3.29 (m, 2H,),
2.81 (dd, 1H, J = 3.9, 14.1 Hz), 2.70 (dd, 1H, J = 3.6 Hz;
13C NMR (75 MHz, D2O): d 177.0, 77.1, 75.9, 72.6, 69.9,
43.0; LC–MS (m/z): 218 (M+Na)+. Anal. Calcd for
C6H13NO6: C, 36.92; H, 6.72; N, 7.18. Found: C, 36.91;
H, 6.77; N, 7.24.
4.1.6.1. 6-Azido-6-deoxy-D-galactonic acid sodium salt
(13). White solid (1.13 g, 95%): [a]D = +64.7 (c 0.4, H2O);
mp 203–204 ꢁC; 1H NMR (300 MHz, D2O): d 4.13 (d, 1H,
J = 1.8 Hz), 3.95 (m, 1H), 3.84 (dd, 1H, J = 9.9 Hz), 3.46
(dd, 1H, J = 2.0 Hz), 3.39 (dd, 1H, J = 6.3, 11.8 Hz),
3.29 (dd, 1H, J = 3.3 Hz); 13C NMR (75 MHz, D2O): d
179.8, 71.8, 71.7, 70.6, 69.2, 54.1; LC–MS (m/z): 266
(M+Na)+. Anal. Calcd for C6H10N3NaO6: C, 29.64; H,
4.15; N, 17.28. Found: C, 29.60; H, 4.10; N, 17.32.
Acknowledgements
4.1.6.2. 6-Azido-6-deoxy-D-mannonic acid sodium salt
15. White solid (1.11 g, 93%): [a]D = +5.1 (c 0.6, H2O);
mp 191–192 ꢁC; 1H NMR (300 MHz, D2O): d 3.95 (d,
1H, J = 5.7 Hz), 3.80 (dd, 1H, J = 2.0 Hz), 3.66 (m, 1H),
3.52 (dd, 1H, J = 9.5 Hz), 3.42 (dd, 1H, J = 2.6,
13.2 Hz), 3.27 (dd, 1H, J = 6.6 Hz); 13C NMR (75 MHz,
D2O): d 180.0, 74.7, 71.8, 70.9, 70.5, 54.4; LC–MS (m/z):
266 (M+Na)+. Anal. Calcd for C6H10N3NaO6: C, 29.64;
H, 4.15; N, 17.28. Found: C, 29.69; H, 4.12; N, 17.23.
`
We thank the Ministere de la Recherche and the Conseil
´
Regional de Picardie for financial support.
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