C-6 Homologues of 1-Deoxynojirimycin
mixture was refluxed for 6 h and cooled to room temperature.
Filtration of the reaction mixture was done to separate solid K2-
CO3. Removal of solvent gave 26 (0.085 g, 89%) as a white
reaction mixture was refluxed for 18 h. The solvent was evaporated
to dryness to afford 7‚HCl as a white foam that was further purified
by column chromatography as a free base [silica, chloroform-
methanol-aq NH3 (8.0:2:0.5) and finally eluted with MeOH-
cryastalline solid. Mp 80-83 °C; [R]27 +36.5 (c 1.65, MeOH);
D
IR (CHCl3) υ 3385, 2927, 1682, 1481, 1454, 1229 cm-1; 1H NMR
(500 MHz, D2O) δ 1.95-2.10 (m, 2H), 2.71 (dd, 1H, J ) 11.0,
13.2 Hz), 3.61 (app t, 1H, J ) 6.4, 8.2 Hz), 3.69 (dd, 1H, J ) 3.3,
9.9 Hz), 3.88 (dt, 1H, J ) 5.5, 10.3 Hz), 3.96 (s, 1H), 4.15 (ddd,
1H, J ) 3.3, 9.6, 11.3 Hz), 4.23-4.32 (m, 2H), 4.73 (d, 1H, J )
11.7 Hz), 4.95 (d, 1H, J ) 11.7 Hz), 7.20-7.31 (m, 5H); 13C NMR
(125 MHz, D2O) δ 23.4 (CH2), 40.0 (CH2), 54.9 (CH), 65.4 (CH2),
65.9 (CH), 75.3 (CH), 75.7 (CH2), 78.8 (CH), 128.2 (CH), 128.5
(CH), 128.5 (CH), 137.2 (C), 156.7 (C); MS (m/z %) 316 (M +
Na+, 100%), 294 (MH+, 34%), 268 (27%), 242 (20%). Anal. Calcd
for C15H19NO5: C, 61.42; H, 6.53; N, 4.78. Found: C, 61.69; H,
6.81; N, 4.42.
chloroform (4:6)] to afford 7 (45 mg, 86%) a light yellow gummy
1
liquid. [R]27 +4.8 (c 1.33, MeOH); H NMR (200 MHz, D2O) δ
D
1.96-2.06 (m, 1H), 2.13-2.22 (m, 1H), 3.00 (app t, 1H, J ) 11.9,
12.4 Hz), 3.37 (app t, 1H, J ) 10.4, 11.3 Hz), 3.56 (dd, 1H, J )
5.0, 12.8 Hz), 3.63 (ddd, 1H, J ) 3.7, 9.27, 11.1 Hz), 3.71 (t, 1H,
J ) 9.6 Hz), 3.82-3.93 (m, 3H); 13C NMR (50 MHz, D2O) δ 30.9
(CH2), 46.2 (CH2), 53.3 (CH), 55.4 (CH), 57.4 (CH2), 67.1 (CH),
72.2 (CH); MS (m/z %):176 (MH+, 100%), 161 (22%), 127 (7%).
Anal. Calcd for C7H16N2O3: C, 47.71; H, 9.15; N, 15.90. Found:
C, 47.57: H, 9.43: N, 16.23.
3-{[(4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl]methyl}-4-
(trimethylsilyl)-1,3-oxazinane (33). The alcohol 32 was trans-
formed into 33 (1:1, diastereomer) by using a procedure similar to
the one used for conversion of alcohol 11 to 10. IR (neat) υ 3018,
(4aR,5S,6R,7S)-5,6,7-Trihydroxyhexahydropyrido[1,2-c][1,3]-
oxazin-1-one (8). A solution of 26 (85 mg, 0.29 mmol) in ethanol
(5 mL) was hydrogenated at atmospheric pressure in the presence
of Pd on charcoal (10%, 3 mg) for 9 h. The reaction mixture was
passed through a short pad of Celite and the solvent was removed
1
2989, 2956, 2399, 1425, 1380, 1251, 1215, 1068 cm-1; H NMR
(200 MHz, CDCl3) δ 0.03 + 0.09 (singlet s, 9H), 1.35-1.55 (m,
7H), 1.70-1.95 (m, 1H), 2.55-2.70 (m, 2H), 3.17-3.37 (m, 1H),
3.65-3.90 (m, 2H), 3.97-4.07 (m, 2H), 4.27 (d, 1H, J ) 10.5
Hz), 4.62 (two sets of d, 1H, J ) 10.6 and 10.4 Hz), 5.20-5.40
(m, 2H), 5.71-5.91 (m, 1H); 13C NMR (50 MHz, CDCl3) δ -2.31
and -2.28 (Si-CH3), 21.89 + 21.94 (CH2), 26.4 + 26.6 (CH3),
26.92 + 26.99 (CH3), 51.0 + 51.2 (CH2), 52.4 (CH), 68.1 + 68.2
(CH2), 78.7 + 80.64 (CH), 80.80 + 81.82 (CH), 83.7 + 85.0 (CH2),
108.9 (C), 118.4 (CH2), 135.0 + 135.3 (CH); MS (m/z %) 322 (M
+ Na+, 45%), 300 (MH+, 100%), 288 (63%). Anal. Calcd for
C15H29NO3Si: C, 60.16; H, 9.76; N, 4.68. Found: C, 60.28; H,
9.52; N, 4.60.
under reduced pressure to afford 8 (56 mg, 95%) as a white solid.
1
Mp 210-212 °C dec; [R]27 +29.5 (c 0.125, MeOH); H NMR
D
(500 MHz, D2O) δ 2.11-2.27 (m, 2H), 2.72 (dd, 1H, J ) 11.2,
13.0 Hz), 3.56 (dd, 1H, J ) 3.2, 9.6 Hz), 3.66 (app t, 1H, J ) 7.3,
7.8 Hz), 3.79 (dt, 1H, J ) 5.5, 10.5 Hz), 3.94 (d, 1H, J ) 1.8 Hz),
4.22-4.34 (m, 2H), 4.36-4.42 (m, 1H); 13C NMR (125 MHz, D2O)
δ 23.3 (CH2), 47.8 (CH2), 55.0 (CH), 65.4 (CH2), 65.5 (CH), 70.5
(CH), 74.2 (CH), 156.8 (C); MS (m/z %) 609 (M + M + M+,
15%), 204 (MH+, 5%), 150 (100%). Anal. Calcd for C8H13NO5:
C, 47.29; H, 6.45; N, 6.89. Found: C, 46.99; H, 6.63; N, 6.79.
(3aS,9aR,10S,10aS)-2,2,10-Trimethylhexahydro-4H-[1,3]dioxlo-
[4,5]pyrido[1,2-c][1,3]oxazine (34). Compound 33 was transformed
to 34 by using a similar protocol as used for the conversion of 10
to 9. [R]27D +11.8 (c 3.15, CHCl3); IR (neat) υ 3018, 2987, 2933,
(3S,4S,5R,6R)-5-Amino-6-(2-hydroxyethyl)piperidine-3,4-di-
ol (7). To a solution of 27 (0.11 g, 0.358 mmol) in DMF (3 mL)
was added LiN3 (0.175 g, 3.58 mmol) and the mixture was heated
to 110 °C for 16 h. When TLC revealed the absence of starting
material, and the reaction mixture was diluted with water (15 mL)
and extracted with ethyl acetate (3 × 15 mL). The ethyl acetate
layer was washed with water, dried over Na2SO4, and concentrated
to give the azide derivative of 27 [0.08 g, 88% after chromato-
1
2856, 2399, 2360, 1382, 1373, 1215, 1097 cm-1; H NMR (200
MHz, CDCl3) δ 0.93 (d, 3H, J ) 6.42 Hz), 1.41(s, 3H), 1.42 (s,
3H), 1.50-1.70 (m, 2H), 1.75 (br d, 1H J ) 13.3 Hz), 1.80 (dt,
1H, J ) 2.7, 10.1 Hz), 2.15 (app t, 1H, J ) 9.6, 10.1 Hz), 2.96
(dd, 1H, J ) 8.7, 10.5 Hz), 3.08 (dd, 1H, J ) 4.1, 9.2 Hz), 3.42
(dt, 1H, J ) 2.7, 11.9 Hz), 3.57 (ddd, 1H, J ) 4.1, 7.3, 10.4 Hz),
3.74 (d, 1H, J ) 8.2 Hz), 4.08 (dd, 1H, J ) 4.6, 11.7 Hz), 4.40 (d,
1H, J ) 7.8 Hz); 13C NMR (50 MHz, CDCl3) δ 13.3 (CH3), 26.7
(CH3), 26.9 (CH3), 29.4 (CH2), 39.4 (CH), 51.5 (CH2), 65.0 (CH),
67.6 (CH2), 75.4 (CH), 84.3 (CH), 86.4 (CH2), 109.9 (C); MS (m/z
%) 228 (MH+, 100%). Anal. Calcd for C12H21NO3: C, 63.41; H,
9.31; N, 6.16. Found: C, 63.66; H, 9.51; N, 5.98.
graphic purification (ethyl acetate-petroleum ether 5:15)]. [R]27
D
+41.25 (c 1.8, CHCl3); IR (CHCl3) υ 2987, 2928, 2856, 2252, 2108,
1662, 1373, 1269, 1230, 1147 cm-1; 1H NMR (200 MHz, CDCl3)
δ 1.43 (s, 6H), 1.58-1.76 (m, 1H), 1.86-2.07 (m, 2H), 2.17 (dd,
1H, J ) 9.8, 10.0 Hz), 3.03 (dd, 1H, J ) 4.0, 9.5 Hz), 3.24-3.34
(m, 2H), 3.41 (dt, 1H, J ) 2.4, 11.9 Hz), 3.52-3.66 (m, 1H), 3.74
(d, 1H, J ) 7.8 Hz), 4.09 (dd, 1H, J ) 4.8, 11.6 Hz), 4.41 (d, 1H,
J ) 7.9 Hz); MS (m/z %) 255 (MH+, 100%), 212 (25%), 200 (50%),
180 (80%), 158 (25%).
(3S,4S,5S,6R)-6-(2-Hydroxyethyl)-5-methylpiperidine-3,4-
diol (31). Compound 34 was transformed to 31 by using a similar
protocol as used for the conversion of 18 to 5. Mp 180-183 °C;
[R]27D +4.0 (c 1.15, MeOH); 1H NMR (500 MHz, D2O) δ 1.13 (d,
3H, J ) 6.4 Hz), 1.71-1.80 (m, 1H), 1.81-1.89 (m, 1H), 2.12-
2.20 (m, 1H), 2.93 (t, 1H, J ) 11.9 Hz), 3.21 (ddd, 1H, J ) 2.3,
9.7, 11.1 Hz), 3.31 (t, 1H, J ) 9.6 Hz), 3.51 (dd, 1H, J ) 5.0, 12.4
Hz), 3.72-3.88 (m, 3H); 13C NMR (125 MHz, D2O) δ 12.4 (CH3),
31.0 (CH2), 38.3 (CH), 46.1 (CH2), 57.9 (CH2), 59.2 (CH), 67.8
(CH), 75.4 (CH); MS (m/z %) 176 (MH+, 100%), 149 (25%). Anal.
Calcd for C8H17NO3: C, 54.84; H, 9.78; N, 7.99. Found: C, 54.86;
H, 9.58; N, 8.06.
The solution of azide derivative of 27 (0.08 g, 0.34 mmol) in
methanol (3 mL) was hydrogenated for 7 h at atmospheric pressure
in the presence of Pd on charcoal (10%) (0.003 g). The reaction
mixture was passed through a short pad of Celite and the solvent
was removed under reduced pressure to afford the amine derivative
of 27 (68 mg, 95%) as a syrup. [R]27 +16 (c 1.75, MeOH); IR
D
(CHCl3) υ 3285, 2987, 2928, 1665, 1373, 1270, 1234, 1024 cm-1
;
1H NMR (200 MHz, CDCl3) δ 1.42 (s, 6H), 1.50-1.71 (m, 1H),
1.75-2.03 (m, 2H), 2.17 (app t, 1H, J ) 9.6, 10.0 Hz), 2.76 (dd,
1H, J ) 8.3, 10.0 Hz), 3.02-3.17 (m, 2H), 3.44 (dt, 1H, J ) 2.5,
12.0 Hz), 3.55 (ddd, 1H, J ) 4.0, 7.5, 10.2 Hz), 3.75 (d, 1H, J )
7.8 Hz), 4.06-4.17 (dd, 1H, J ) 4.8, 11.4 Hz), 4.42 (d, 1H, J )
7.8 Hz); MS (m/z %) 228 (M+, 100%).
Acknowledgment. We thank Dr. P. R. Rajmohan and Mrs.
U. D. Phalgune for special NMR experiments. S.G.D. and M.S
thank UGC and CSIR, respectively, New Delhi for the award
of Research Fellowships. Financial support by the DBT, New
Delhi is gratefully acknowledged.
To a solution of the amine derivative of 27 (68 mg, 0.097 mmol)
in distilled methanol (3 mL) was added 2 mL of 6 N HCl and the
J. Org. Chem, Vol. 71, No. 22, 2006 8487