6910
C. C. Joseph et al. / Tetrahedron 58 (2002) 6907–6911
H-6a/6b), 3.97 (t, 1H, H-3), 3.87 (d, 1H, H-2), 2.96–2.73
(m, 2H, H-4/5), 1.42, 1.32 (s, 6H, CMe2). 13C NMR (D2O,
75 MHz) d 174.98 (CvO), 112 (qC), 75.66, 75.49 (C-2/3),
73.59 (C-4), 68.30 (C-5), 43.57 (C-6), 27.41 and 25.38
(CMe2). Anal. calcd for C9H15NO5: C 49.76; H 6.96; N
6.45. Found (%): C 49.48; H 6.86; N 6.32.
4.1.9. Methyl 6-deoxy-6-iodo-2,3,4,5-tetra-O-acetyl-D-
gluconate (14). A stirred mixture of methyl 2,3,4,6-tetra-
O-acetyl-D-gluconate 13, (1.0 g, 2.65 mmol) chloro-
trimethylsilane (1.15 g, 10.58 mmol, 4 equiv.) and sodium
iodide (1.59 g, 10.6 mmol, 4 equiv.) in dichloromethane
(10 mL) mainatained under nitrogen was set aside at room
temperature for 18 h. The mixture was treated with a
mixture of acqueous 5% sodium thiosulfate and saturated
sodium hydrogen carbonate solution (50 mL, 1:1) and the
separated organic layer was washed with a mixture of 5%
sodium thiosulfate and saturated sodium hydrogen carbon-
ate (25 mL, 1:1), brine (50 mL), dried (Na2SO4) and
concentrated in vacuo. Recrystallization of the crude
crystalline material from ether afforded 14 (1.12 g, 87%)
as white crystals. Mp 124–1258C, [a]D¼þ18 (c 1, CHCl3);
4.1.6. (3R,4R,5R,6R )-Tetrahydroxyazepane (1,6-
dideoxy-1,6-imino-D-mannitol) (1). A solution of com-
pound 10 (300 mg, 1.38 mmol) in tetrahydrofuran (10 mL)
containing borane–tetrahydrofuran (1.5 mL) was heated
under reflux for ca. 20 h, cooled to room temperature and
concentrated in vacuo. A solution of the residue 11 in
methanol (10 mL) was treated with two drops of concen-
trated hydrochloric acid and kept at room temperature for
24 h, concentrated in vacuo and the resultant material was
dissolved in water (15 mL) and extracted with ether
(2£10 mL). The aqueous layer was concentrated in vacuo
and water (3£10 mL) was distilled in vacuo from the
residue to give a crude white solid which was recrystallized
from methanol/ether (5:1, v/v) to give compound 1
(220.6 mg, 80%) as the HCl salt. Mp 184–1868C, lit.2b
mp 183–1858C; [a ]D¼245 (c 1, H2O), lit.2b [a ]D¼238;
1H NMR (D2O, 300 MHz) d 3.86 (m, H-2), 3.62 (s, H-3),
2.71 (dd, H-1b, J1b,2¼8.3 Hz, J1b,1a¼13.3 Hz), 2.63 (dd, 1H,
J1a,2¼3.38 Hz, J1a,1b¼13.3 Hz). 13C NMR (D2O, 75 MHz)
d 75.73, 73.08 (C-2/3), 53.84 (C-1). Anal. calcd for
C6H14ClNO4: C 36.10, H 7.07, N 7.02. Found (%): C
35.92; H 6.98; N 6.91.
n
max(KBr) 1730 (acetate, ester CvO) cm21 1H NMR
;
(CDCl3, 300 MHz), d 5.52 (t, 1H, H-3, J3,2¼4.2 Hz), 5.39
(dd, 1H, H-4, J4,3¼4.2 Hz, J4,5¼6.85 Hz), 5.20 (d, 1H, H-2,
J2,3¼4.3 Hz), 4.96–4.90 (m, 1H, H-5), 3.8 (s, 3H, OMe ),
3.4 (dd, 1H, H-6a, J6a,5¼3.4 Hz, J6a,6b¼11.4 Hz), 3.2 (dd,
1H, H-6b, J6b,5¼5.1 Hz, J6b,6a¼11.4 Hz), 2.2, 2.1, 2.1, 2.0
(s, 12H, 4£COCH3) 13C NMR (CDCl3, 300 MHz) d 169.69,
169.53, 169.43 (2£) (4£COCH3), 167.18 (CvO, ester),
71.26 (C-2), 70.62, 69.75 (C-4/5), 68.33 (C-3), 52.84
(OMe), 20.77, 20.69, 20.42 (2£), (4£COCH3), 2.37 (C-6);
Anal. calcd for C15H21IO10: C 36.90; H 4.34. Found (%): C
37.05; H 4.33.
4.1.10. Methyl 6-azido-6-deoxy-2,3,4,5-tetra-O-acetyl-D-
gluconate (15). A stirred solution of 14 (1.09 g, 2.05 mmol)
in N,N-dimethylformamide (5 mL) was treated with lithium
azide (0.462 g, 10.27 mmol, 5 equiv.) and set aside at 608C
for 20 h. The mixture was poured into ice-water (20 mL)
and the product extracted with ethyl acetate (2£30 mL). The
combined organic layers were washed once with water
(20 mL), brine (30 mL), dried (Na2SO4) and concentrated in
vacuo to give crystalline material on standing at room
temperature. Recrystallization from ether gave compound
15 (712 mg, 86%) as white crystals. Mp 68–698C,
[a ]D¼þ16 (c 1, CHCl3); nmax(neat) 2105 (–NvNvN),
4.1.7. 2,3,4,6-Tetra-O-acetyl-D-glucono-1,5-lactone (12).
stirred solution of D-glucono-1,5-lactone (5 g,
A
28.09 mmol) in acetic anhydride (30 mL) containing
trifluoroacetic acid (2.5 mL) was kept at room temperature
for 3 h. The mixture was concentrated in vacuo and toluene
(3£20 mL) was distilled in vacuo from the residue to give
12 as a colourless syrup (9.15 g, 94%). [a]D¼þ76.1 (c 1,
CHCl3), lit.18 þ79.7; nmax(neat) 1720–1730 (acetate CvO,
1
lactone CvO) cm21; H NMR (CDCl3, 100 MHz) d 5.58
(m, 1H, H-3), 5.37 (m, 1H, H-4), 5.16 (d, 1H, H-2), 4.60 (m,
1H, H-5), 4.39–4.26 (m, 2H, H-6, 60), 2.25–2.00 (m, 4s,
each 3H, 4£acetyl CH3).
1735 (acetate, ester CvO) cm21 1H NMR (CDCl3,
;
300 MHz) d 5.55 (t, 1H, H-3, J3,2¼4.4 Hz, J3,4¼4.4 Hz),
5.46 (dd, 1H, H-4, J4,3¼4.4 Hz, J4,5¼6.8 Hz), 5.2 (d, 1H,
H-2, J2,3¼4.4 Hz), 5.06–5.03 (m, 1H, H-5), 3.75 (s, 3H,
OMe ), 3.53 (dd, 1H, H-6a, J6a,5¼3.9 Hz, J6a,6b¼13.4 Hz),
3.39 (dd, 1H, H-6b, J6b,5¼6.1 Hz, J6b,6a¼13.4 Hz), 2.18,
2.12, 2.09, 2.08 (s, 12H, 4£COCH3). 13C NMR (CDCl3,
75 MHz), d 169.52, 169.40, 2£169.30 (4£COCH3), 168.94
(CvO, ester), 70.33 (C-2), 69.23, 69.12 (C-3/4), 68.18
(C-5), 52.72 (OMe), 49.97 (C-6), 22.43, 20.62, 20.46, 20.37
(4£COCH3). Anal. calcd for C15H21N3O10: C 44.67; H
5.25; N 10.42. Found C 44.83; H 5.16; N 10.34%.
4.1.8. Methyl 2,3,4,6-tetra-O-acetyl-D-gluconate (13). A
stirred solution of 12 (9.0 g, 26.0 mmol) in methanol
(100 mL) containing p-toluenesulfonic acid (150 mg) was
kept at room temperature for 1 h when analysis (TLC)
indicated completion of the reaction. The mixture was
neutralized by ion-exchange resin (IRA 400, HCO23 form),
filtered, and the filtrate concentrated in vacuo to give white
crystals which were recrystallized from methanol to give 13
(9.5 g, 97%). Mp 114–1168C, lit.11 mp 111–1128C;
[a ]D¼þ20.6 (c 1, CHCl3), lit.11 [a]D¼þ16.8; nmax(KBr)
1730 (acetate, ester CvO) cm21
;
1H NMR (CDCl3,
4.1.11. 6-Amino-6-deoxy-D-glucono-1,6-lactam (3S,4R,
5R,6R-tetrahydroxy-azepan-2-one) (16). A solution of
the protected azide 15 (600 mg, 1.49 mmol) in methanol
(20 mL) containing a catalytic amount of potassium cyanide
(10 mg) was set aside for 48 h. The mixture was filtered
through a layer of silica gel and the filtrate concentrated in
vacuo to give a brown residue which was purified by
passage through a short column of silica gel (dichloro-
methane–methanol, 4:1) to give a colourless gel which was
not characterized but used immediately in the following
300 MHz): d 5.71 (t, 1H, H-3), 5.31 (d, 1H, H-2), 5.19
(dd, 1H, H-4), 4.14 (m, 2H, H-6), 3.86 (d, 1H, H-5), 3.74 (s,
3H, OMe), 3.03 (br s, 1H, OH), 2.17, 2.16, 2.14, 2.10 (s,
12H, 4£COCH3). 13C NMR (CDCl3, 75 MHz) d 171.10
(CvO ester), 170.43, 169.70, 167.30 (CvO acetate), 71.55
(C-2), 70.66, 69.44 (C-3/4), 68.34 (C-5), 64.64 (C-6), 52.75
(OCH3-methoxy), 20.70, 2£20.50, 20.39 (4£COC H3).
Anal. calcd for C15H22O11: C 47.62; H 5.86. Found (%):
C 47.36; H 5.81.