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G. Jayachitra et al.
PAPER
[a]D28 +3.1 (c 0.005, CHCl3) [Lit.8p,10 [a]D25 –2.5 (c 0.71, CHCl3)].
IR: 3341, 3291, 2918, 2853, 1461, 1376, 1042 cm–1.
[a]D22 +14.4 (c 0.008, CHCl3).
IR: 3426, 2995, 2949, 1636, 1375, 1216, 1165, 1073 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.88 (t, J = 6.8 Hz, 3 H), 1.11–1.39
(m, 24 H), 1.5–1.64 (m, 2 H), 2.88 (br s, 3 H), 3.3–3.5 (m, 2 H),
3.78–3.91 (m, 2 H), 4.15 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.0, 22.6, 26.4, 28.5, 29.3, 29.6,
29.8, 31.9, 59.8, 73.2, 79.2, 80.8.
1H NMR (300 MHz, CDCl3): d = 1.31 (s, 3 H), 1.47 (s, 3 H), 1.74
(d, J = 4.5 Hz, 1 H), 3.77 (d, J = 9.8 Hz, 1 H), 3.96 (dd, J = 3.8, 9.8
Hz, 1 H), 4.33 (t, J = 3.8 Hz, 1 H), 4.56 (d, J = 3.8 Hz, 1 H), 4.58 (d,
J = 3.0 Hz, 1 H), 4.64 (d, J = 3.0 Hz, 1 H), 5.78 (d, J = 3.0 Hz, 1 H).
MS (LC): m/z = 225 [M + Na]+.
HRMS (ESI): m/z [M + H]+ calcd for C18H38NO2: 300.2902; found:
300.2894.
3,6-Anhydro-1,2-O-isopropylidene-5-O-mesyl-b-L-idofuranose
(14)
A soln of MsCl (0.574 mL, 7.42 mmol) in CH2Cl2 (5 mL) was added
to a mixture of 13 (1 g, 4.95 mmol) and Et3N (3.44 mL, 24.75
mmol) in CH2Cl2 (15 mL) at 0 °C. The mixture was brought to r.t.
and stirred for 4 h and then extracted with CH2Cl2 and the combined
extracts were washed with brine, dried (Na2SO4), and concentrated
in vacuo. The residue was purified by column chromatography
(hexane–EtOAc, 5:1) to give 14 (1.18 g, 86%) as a white solid; mp
102–104 °C.
[a]D30 +20.7 (c 0.01, CHCl3).
IR: 2986, 2935, 1627, 1350, 1169, 1078 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.31 (s, 3 H), 1.48 (s, 3 H), 3.04
(s, 3 H), 4.03–4.07 (m, 2 H), 4.58 (d, J = 3.6 Hz, 1 H), 4.61 (d,
J = 3.2 Hz, 1 H), 4.85 (d, J = 3.2 Hz, 1 H), 5.09 (d, J = 3.0 Hz, 1 H),
5.80 (d, J = 3.4 Hz, 1 H).
(2R,3R,4S)-4-Acetamido-2-tetradecyltetrahydrofuran-3-yl
Acetate (3b)
To an ice-cooled, stirred soln of 3a (20 mg, 0.07 mmol) in anhyd
CH2Cl2 (5 mL) was added Et3N (0.05 mL, 0.16 mmol), Ac2O
(0.016 mL, 0.33 mmol), and DMAP (catalytic amount). The tem-
perature was allowed to reach r.t. and the mixture was stirred for 4
h. The mixture was diluted with CH2Cl2 and the organic layer was
washed with sat. NH4Cl soln, H2O, and brine, and dried (anhyd
Na2SO4). The solvent was removed on a rotary evaporator and the
residue was purified by column chromatography (silica gel, hex-
ane–EtOAc, 2:1) to afford 3b (24 mg, 94%) as an amorphous solid;
mp 70–72 °C.
[a]D28 +7.4 (c 0.002, CHCl3).
IR: 3258, 2922, 2852, 1744, 1646, 1468, 1374, 1230, 1058 cm–1.
1H NMR (300 MHz, CDCl3): d = 0.88 (t, J = 6.8 Hz, 3 H), 1.17–1.35
(m, 24 H), 1.35–1.55 (m, 2 H), 1.97 (s, 3 H), 2.10 (s, 3 H), 3.45 (dd,
J = 4.5, 9.06 Hz, 1 H), 3.86 (m, 1 H), 4.15 (m, 1 H), 4.24 (dd,
J = 6.0, 9.8 Hz, 1 H), 5.08 (dd, J = 3.0, 4.5 Hz, 1 H), 5.75 (d, J = 5.3
Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 14.0, 20.8, 22.6, 23.1, 26.2, 28.7,
29.3, 29.5, 29.55, 31.9, 57.0, 71.0, 78.2, 80.1, 169.9, 170.3.
MS (LC): m/z = 303 [M + Na]+.
3,6-Anhydro-5-azido-5-deoxy-1,2-O-isopropylidene-a-D-gluco-
furanose (15)
A mixture of 14 (1 g, 3.57 mmol) and NaN3 (2.785 g, 42.85 mmol)
in DMF (15 mL) was heated at 120 °C for 2 d. The mixture was
poured into H2O and extracted with EtOAc. The combined extracts
were washed with sat. brine, dried (Na2SO4), and concentrated in
vacuo. The residue was column chromatography (hexane–EtOAc,
24:1) to give 15 (0.51 g, 63%) as a syrup.
HRMS (ESI): m/z [M + Na]+ calcd for C22H41NNaO4: 406.2933;
found: 406.2944.
[a]D29 +32.5 (c 0.02, CHCl3).
IR: 2987, 2108, 1378, 1285, 1227, 1073 cm–1.
3,6-Anhydro-1,2-O-isopropylidene-5-O-(4-nitrobenzoyl)-b-L-
idofuranose (12)
To a soln of 6 (2.0 g, 9.9 mmol) in THF (25 mL) was added Ph3P
(9.9 g, 34.65 mmol), 4-nitrobenzoic acid (5.785 g, 34.65 mmol),
and DIAD (6.82 mL, 34.65 mmol) under 0 °C. The mixture was
brought up to r.t. and stirred overnight. The solvent was removed
from the mixture under reduced pressure. The residue was column
chromatographed (hexane–EtOAc, 7:1) to give 12 (3.09 g, 89%) as
a yellow solid; mp 100–105 °C.
1H NMR (200 MHz, CDCl3): d = 1.32 (s, 3 H), 1.48 (s, 3 H), 3.66–
3.74 (m, 2 H), 3.98 (m, 1 H), 4.47 (d, J = 3.6 Hz, 1 H), 4.54 (d,
J = 3.6 Hz, 1 H), 4.88 (t, J = 3.6 Hz, 1 H), 5.92 (d, J = 3.0 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 26.6, 27.3, 61.2, 68.6, 83.0, 84.8,
85.9, 107.0, 112.7.
MS (LC): m/z = 227 [M]+.
[a]D29 +59.0 (c 0.007, CHCl3).
(2R,3R,4R)-4-Azido-2-[(Z)-tetradec-1-enyl]tetrahydrofuran-3-
ol (18)
IR: 3111, 3082, 2995, 2942, 2884, 1752, 1607, 1529, 1285, 1081,
719 cm–1.
1H NMR (200 MHz, CDCl3): d = 1.33 (s, 3 H), 1.48 (s, 3 H), 3.99
(d, J = 10.2 Hz, 1 H), 4.19 (dd, J = 3.7, 11.0 Hz, 1 H), 4.64 (m, 2 H),
4.87 (d, J = 3.7 Hz, 1 H), 5.45 (d, J = 3.7 Hz, 1 H), 5.86 (d, J = 3.7
Hz, 1 H), 8.16–8.34 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 26.5, 27.3, 29.6, 72.7, 78.1, 84.0,
85.4, 85.7, 106.5, 112.6, 134.6, 150.8, 163.5.
MS (ESI): m/z = 352 [M + 1]+.
To 15 (0.4 g, 1.76 mmol) was added 60% aq AcOH (10 mL) and
concd HCl (catalytic amount) and the mixture was stirred at r.t. for
12 h. The mixture was neutralized with solid NaHCO3 until pH 7,
filtered, and washed with EtOAc. The organic layer was dried
(Na2SO4), concentrated in vacuo, and purified by column chroma-
tography (silica gel, hexane–EtOAc, 2:1) to give 16 (0.28 g, 85%)
as a syrup as a mixture of anomers (~1:1).
[a]D31 +107.3 (c 0.01, MeOH).
To a soln of 16 (0.2 g, 1.06 mmol) in 80% aq MeOH (10 mL) was
added NaIO4 (0.46 g, 2.1 mmol); the mixture was stirred for 30 min.
Then the solvent was removed under reduced pressure and the resi-
due was extracted with EtOAc and the combined extracts were
dried (Na2SO4) and concentrated to afford crude 17.
To a precooled (–40 °C) soln of Wittig salt [Me(CH2)12]Ph3P+Br–
(1.065 g, 2.4 mmol) in THF (25 mL) was slowly added t-BuOK
(0.27 g, 2.43 mmol) under N2. The orange soln was stirred at this
temperature for 1 h and then it was then cannulated to a soln of 17
3,6-Anhydro-1,2-O-isopropylidene-b-L-idofuranose (13)
A soln of 12 (2.8 g, 7.97 mmol) in THF–H2O (1:1, 30 mL) was add-
ed LiOH·H2O (0.67 g, 15.95 mmol) and the mixture was stirred for
1 h. Then it was extracted with EtOAc and the combined extracts
were washed with brine, dried (Na2SO4), and concentrated in vacuo.
The residue was purified by column chromatography (hexane–
EtOAc, 4:1) to give 13 (1.2 g, 75%) as a white solid; mp 125–130
°C.
Synthesis 2010, No. 1, 115–119 © Thieme Stuttgart · New York